Download MBBS Biochemistry PPT 48 Carbohydrate Metabolism Lecture Notes

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Synopsis

Introduction to Metabolism
Ingestion of Carbohydrates
Digestion and Absorption Of Carbohydrates.

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Transportation and Uptake of Glucose by cells.
Utilization/Assimilation of Carbohydrates.
Fate of Glucose ,Galactose and Fructose
(Associated Anabolic and Catabolic Pathways)
Excretion Of Metabolic end products of Carbohydrates

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Applied aspects/Associated Metabolic

Disorder/Inborn Errors of Carbohydrate Metabolism.
Various Fates of Glucose/Metabolic

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Pathways Associated to Glucose.

Complete Oxidation Of Glucose

1.

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Glycolysis and Rapaport Leubering

Cycle

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2. PDH Complex Reaction
3.

TCA cycle

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Glycogen Metabolism

1. Glycogenesis
2. Glycogenolysis

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HMP shunt/Pentose Phosphate

Pathway

Gluconeogenesis

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Cori's Cycle/Glucose Alanine Cycle.
Blood Glucose Regulation
Glucose Tolerance Test (GTT)
Glycosuria
Diabetes Mellitus.

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Galactose metabolism
Galactosaemia
Fructose Metabolism
Essential Fructosuria

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Irreversible Reactions-

Different set of Enzyme required.
Non equilibrium Reactions.
Regulatory steps.

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E2

C

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D

E3

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Types Of

Biochemical Reactions

Oxidation/Dehydrogenation

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/Hydroxylation

Reduction
Hydrolytic

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Carboxylation
Decarboxylation
Phosphorylation
Dephosphorylation
Amination

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Deamination
Isomerization
Hydration
Dehydration

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Metabolic Pathway

Metabolic pathway is a series of

well defined and significant

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biochemical reactions followed

one after another giving

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intermediate products and finally

end product of the pathway.
A Precursor of the pathway (A)
E1

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B
E2
C Intermediates of the pathway (B,C,D)
E3

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D
E4

E End Product of the pathway (E)

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Organization of Pathways

Pathways consist of sequential steps.
The enzymes may be separate.

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May form a multienzyme complex.
May be a membrane-bound system.
New research indicates that

multienzyme complexes are more

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common than once thought.


Mutienzyme complex

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Separate

enzymes

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Membrane

Bound System

Organization of Pathways

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Closed Loop

(intermediates recycled)

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Linear

Spiral

(product of rxns

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(same set of

are substrates for

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enzymes used

subsequent rxns)

repeatedly)

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Compartmentalization Of

Metabolic Pathways

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Compartmentalization

of pathways permits

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integration and

regulation of

metabolism.

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Phosphoryl-group Transfer

Types Of Metabolic Pathway

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Catabolic/Degradative /Energy

Generating/ATP producing

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Pathways/Exothermic.

Anabolic/Synthetic/Energy Utilizing/
ATP Using Pathways/Endothermic.
Catabolic pathways involve

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oxidative reactions producing

reducing equivalents-

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NADH+H+ and FADH2.

Catabolic pathways converge to

few end products.

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Anabolic pathways

diverge to

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synthesize many

biomolecules.

.

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Some pathways serve

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both in catabolism and

anabolism ,those are

Amphibolic pathways.

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Amphibolic Pathways occur at

the crossroads of metabolism.

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Amphibolic pathways links

between Anabolic and Catabolic

pathways.

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Regulation of Metabolic

Pathways

Regulation means stimulation and

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inhibition of pathways as per

cellular need.

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Hormones regulate the metabolic

pathways.

Metabolic pathways are regulated to

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allow the organism to respond to

changing conditions.
Every metabolic pathway has its

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specific regulatory enzymes/key

enzymes.

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Hormones regulate by either

stimulating /inhibiting the

regulatory/key enzymes of the

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pathway.

Modes Of Metabolic

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Regulation

? Allosteric regulation

? Covalent modification

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? Control of enzyme levels

? Compartmentalization

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? Metabolic specialization of organs


Feedback inhibition ?

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product of pathway down

regulates activity of early

step in pathway

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Feedforward activation ?

metabolite produced early in

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pathway activates down stream

enzyme
Regulating Related Catabolic

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and Anabolic Pathways

Anabolic & catabolic pathways involving

the same compounds are not the same.

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Some steps may be common to both
Others must be different - to ensure that

each pathway is spontaneous.

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This also allows regulation mechanisms to

turn one pathway onn and the other off.

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Modes Of Enzymes Regulation

Alteration in membrane permeability.
Conversion of Inactive to Active form.
Stimulation of mRNA translation.

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Induction of new mRNA formation.
Repression of mRNA formation.
Knowledge of normal

metabolism is essential for :

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Understanding adaptations of

?Starvation
?Exercise

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?Pregnancy and lactation.

Understanding of metabolic

disorders.

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Abnormal Metabolism Is Due To

vNutritional Deficiencies
vEnzyme Defects

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vHormonal Defects
vDrug and Toxin

Interactions
Normal Enzyme and

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Hormonal activities gives

normal metabolism and

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health to human body.

Defect in Enzymes and

Hormones derange the

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normal metabolism.

Derangement in Metabolism

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Any defect or derangement in

normal pattern of metabolism

leads to metabolic disorders.

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Mutation in Genes of Enzymes,

forms defective Enzymes.

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Congenital defect of Enzyme leads

to Inborn Error Of Metabolism.
Inborn Error Of Metabolism

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Congenital deficiency of

any single Enzyme of a

metabolic pathway leads to

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Inborn Errors of

Metabolism.

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Enzyme Deficiency of a

Metabolic Pathway

Blocks the metabolic reaction.

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Blocks the metabolic pathway.
Accumulates and excrete

intermediate product of the pathway.

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No formation of end product of the

pathway.

Affects other interrelated metabolic

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pathways.
Methods Used to Study

Metabolism

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Metabolic Reactions/Metabolic

Pathways were studied :

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Using whole organism/Cellular

fractions

Using Metabolic Probes.

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Using Radioisotopes.

Ingestion Of Dietary

Carbohydrates

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Why To Eat Dietary

Carbohydrates?

Carbohydrates predominantly

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not biosynthesized by human

body.

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Carbohydrates are required

for metabolic and structural

role to human body.

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Precursors for biosynthesis of

nutritionally non essential

amino acids.

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To get the role of dietary fiber .
(Cellulose , Hemicellulose ,Pectin

Lignin, Agar)

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Carbohydrate is a primary

source of energy and a

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preferred fuel of the body.

60-80% of energy intake comes

from Carbohydrates.

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Carbohydrate foods are

cheap, readily available and

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palatable.
" Fat Burns Under The

Flame Of Carbohydrates"

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For the complete oxidation of Fats

there needs Carbohydrates.

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How much Carbohydrates To Eat?

OR

Amount Of Carbohydrates To Be

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Eaten
R.D.A for dietary Carbohydrates =
400- 600 gm/day

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(Depends upon the human activities)

1 gram of Carbohydrate when

completely oxidized in the body

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generates 4 kcal of energy.

Calorific value for dietary

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Carbohydrates is 4 kcal.
Dietary forms

Of

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Carbohydrates

and their

Rich Sources

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What Forms Of Dietary

Carbohydrates Eaten?
Dietary Forms Of

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Rich sources of Food

Carbohydrates
Monosaccharides

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Glucose

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Fruits

Honey and Fruits

Fructose

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Disaccharides

Sucrose

Common table sugar, Sweets recipes,

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Juices, Tea

Lactose

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Milk and Milk Products

Maltose

Malt grain ,Germinating seeds

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Polysaccharides

Starch

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Grains, Pulses, Potatoes, Tubers

,Tapioca

(Predominant)

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Glycogen

Meat, Chicken, Liver

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(NonVeg Eater)

Cellulose

Whole grains ,Dates, Green leafy

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Vegetables ,Raw vegetables,

Cellulose is rich in

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unrefined whole grain

(Husk).

Cellulose is poor in

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refined grains (Kernel).
Significance Of Cooking

and

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Mastication of Food

During cooking there is hydrolysis of

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many bonds of food constituents.

Cooking makes the food:

Tasty

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Soft
Chewable
Eatable
Easily Digestible
Mastication of food takes place in mouth.

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Mastication is biting and chewing of

food with teeth to break large morsals of

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food into small particles mixed with

saliva to form bolus.

Proper mastication of food in mouth

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facilitates for good digestion and

absorption of food constituents.

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Digestion

of

Dietary Carbohydrates

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by

Specific Glycosidases
Digestion of carbohydrate involves

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cleavage of Glycosidic bonds

present in Polysaccharides and

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Disaccharides to form free

Monosaccharides.

Glycosidases are Carbohydrate

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Digesting Enzymes which cleaves

specific glycosidic bonds.

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There are specific Glycosidases for

each Carbohydrate form.

Digestion of Monosaccharides

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Dietary Monosaccharides /

Simple Sugars (Free Glucose

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/Free Fructose)

Requires no digestion and

are ready for absorption.

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Monosaccharides are readily

absorbable forms from GIT

lumen.

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Simple sugars require very

less time to reach blood and

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cells.

Drinking Glucon?D give

instant energy in very few

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minutes.

Digestion Of Disaccharides

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Digestion of Disaccharides takes

place in small intestine.

Disaccharides are digested by specific

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Disaccharidases.

Lactase, Maltase, Sucrase (Invertase)

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and Isomaltase are specific

Disaccharidases.
Lactase cleaves (1-4)

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glycosidic bond of Lactose

Maltase cleaves (1-4)

glycosidic bond of Maltose

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Sucrase cleaves 1 2

glycosidic bond of Sucrose

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Lactose Lactase Glucose + Galactose

Maltose Maltase Glucose + Glucose

Sucrose Sucrase Glucose + Fructose

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Digestion Of Polysaccharides

Starch and Glycogen are

digested by enzyme Amylase.

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Amylase is a Starch and

Glycogen digesting enzyme.

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Types of Amylases

Salivary Amylase
(Mouth-Salivary Juice)
Pancreatic Amylase

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(Small Intestine-Pancreatic Juice)

Amylase cleaves -(1-4) glycosidic

bonds of Starch , Dextrin and Glycogen.

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Chloride ion is an

inorganic cofactor for

-Amylase activity.

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Digestion of Starch and Glycogen

begins in mouth by the action of

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salivary Amylase (pH- 6.6)

Digestion of Starch is incomplete

in mouth.

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Dextrin is an intermediate of

Starch digestion.
Significant and complete

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digestion of Starch occurs in

intestine by Pancreatic

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Amylase(pH 7.1).

Maltose and Isomaltose are

end products of Starch

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digestion by Amylase activity.

Maltose and Isomaltose are then

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hydrolyzed by Maltase and

Isomaltase to liberate free Glucose

units.

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Thus end product of Starch

digestion is many Glucose units.
No Digestion of Dietary Cellulose

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Dietary Cellulose is not digested

in human GIT due to absence of

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Cellulase digesting enzyme

Cellulose.

Cellulase in ruminants cleaves (1-

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4) glycosidic bonds of Cellulose to

form Cellobiose.

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Dietary Oligosaccharides

are not digested by GIT

enzymes.

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Bacterial enzymes act upon it

to produce gas.

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Thus Oligosaccharides of

diet apt to cause flatulence.
No Digestion Of Carbohydrates in

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Stomach

Gastric juice of stomach has:

vNo specific Glycosidase for

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Carbohydrate digestion.

vNo optimal pH for enzyme action.

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Salivary Amylase of mouth carried to

stomach along with food bolus is

inhibited by vey low pH of gastric juice.

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Monosaccharides

is an End Product Of

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Carbohydrate Digestion.
End products of

Carbohydrate digestion are :

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Monosaccharides- Glucose ( 80%)
Galactose
Fructose

Absorption Of Monosaccharides

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Monosaccharides an end product

of Carbohydrate digestion are

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absorbable forms.

Site of Absorption :

Small Intestine

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vDuodenum
vUpper part of Jejunum
Relative Rates of Absorption

Coefficient /Relative rates of absorption of

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different Monosaccharides in intestine:

Glucose= 100
Galactose = 110

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Fructose = 43
Mannose = 20
Xylose = 15
Arabinose = 09

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Modes of Absorption

Glucose and Galactose ? (Complete)
Active Transport mechanism
Fructose ?

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Facilitated Diffusion
Pentose-
Simple Passive Diffusion.
Absorption Of Glucose

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Glucose absorption by active

transport mechanism.

Sodium dependent Symport

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Co-Transport type.

(Secondary Active Transport)

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Glucose Transportation Requires:

Protein carrier molecule

Na + ions

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Sodium-Potassium ATPase.

ATP

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Glucose and Galactose are

absorbed by same Glucose

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transporter.

Absorption of Glucose and

Galactose is complete since it

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is by active transport

mechanism.

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Absorbed Glucose ,Galactose

and Fructose simply diffuse in

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blood capillaries and carried

from intestine to Liver by

Hepato Portal Circulation.

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Thus Liver is the first station to

receive dietary Carbohydrates.
From Liver Carbohydrates

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are then distributed to

remaining all tissues and

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cells of human body through

systemic circulation of

blood.

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Disorders

Of

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Carbohydrate

Digestion

and

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Absorption.
Lactose Intolerance

Lactose Intolerance

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Dietary Lactose not

tolerated.

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No digestion and

absorption of dietary

(Milk) Lactose.

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Causes

Congenital / Acquired
Deficiency of Lactose

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digesting enzyme

`Lactase'

Biochemical Alterations

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Dietary Lactose not digested due

to deficient Lactase.

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Lactose remains in GIT and is

acted upon by bacterial enzymes

to Lactic acid and Gas (H2,CO2,

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Methane).
Lactic acid and Lactose are

washed out through fecal

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excretion.

Loss of body water and

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electrolytes through feces.

Water and Electrolyte

imbalance/Dehydration

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(Mixed Type Dehydration)

Clinical Manifestations

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Lactic acid excretion causes

irritant osmotic diarrhea.

Gas excretion causes flatulence.

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Abdominal cramps.
Increased motility of intestine.
Weakness.
Confusion.
Diagnosis

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Benedicts Test on stool

specimen .

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Positive result of

Benedicts test confirms

diagnosis.

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Management

Lactose intolerance is managed

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by avoiding dietary intake of

foods (Milk and Milk Products)

containing Lactose.

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Intake of Curds which contains

Lactobacillus.
Incidence and Prevalence

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More than half of world

population is suffering from

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Lactose Intolerance.

90 % Asians

(More in South India)

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10 % Africans.

Glycaemic Index (GI) Of

Carbohydrate Foods.

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Glycemic index (GI)

measures an increase in

post prandial(PP) blood

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Glucose after ingestion of

dietary Carbohydrates.

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GI of a food is calculated in

comparison with an

equivalent amount of Glucose

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liberated by food such as

bread/boiled rice.
Glycaemic Index Of Common

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Foods

Foods

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Glycaemic Index

Potatoes, Corn Flakes

80-90

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Whole Wheat Bread,

70-79

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White Rice

Brown Rice, Bananas

60-69

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Buck Wheat, Frozen Peas.

50-59

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Peas, Beans

40-49

Legumes, Milk, Ice

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< 40

cream, Peanuts.
Factors Affecting GI

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Degree and pattern of rise in post

prandial Glycaemia depends on:

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Amount of dietary Carbohydrate

ingested.

Type of dietary Carbohydrate ingested.

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Extent of dietary Carbohydrate

digested and absorbed in GIT.

Steep rise of post prandial

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Glucose is noted on ingestion

of refined sugars.

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Refined free sugars enter the

blood and body pleasantly,

imperceptibly and effortlessly

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within very less time.
Less steep rise of post prandial

Glucose is noted on ingestion of

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dietary complex carbohydrates like

Starch/Cellulose.

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Starchy food takes more time as

it takes effort to chew and less

palatable than refined and simple

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sugar.

Factors Reducing Post Prandial

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Glycaemia
Eating complex

Carbohydrates (Starch/

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Glycogen).

Inadequate cooking of

Starch.

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Inadequate chewing and

mastication of eaten food.

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Eating non digestible

Carbohydrate Cellulose.

Eating large particle size of food.

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Presence of Enzyme inhibitors in

food.

Presence of Protein or fat in

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association with Carbohydrates.
Calorific value of sugar and

starch is same 4 Kcal/gm.

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One who consumes sweets

and refined sugars get more

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calories and prone to grow

over weight.

Importance to know GI of

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Foods
Foods with high Glycaemic

Index (GI) increases the post

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prandial glycaemia.

Foods with low GI decreases

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the post prandial glycaemia.

Knowing the GI value of

food helps:

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vIn planning a rational diet

for patients of Diabetes

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mellitus.

vIn planning diet for persons to

gain and loose weight.

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Uptake Of Glucose Within

The Cells

Absorbed Glucose is carried

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from intestine through Hepato

portal circulation and reaches

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the Liver.
Glucose is transported into the

cells with the help of specific

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membrane bound Proteins

termed Glucose Transporters.

Glucose Transporters

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Glucose Transporters (GluT) are

Transmembrane proteins present

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in cell membranes

They help in uptake of Glucose from

blood into cells.

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Glucose Transporters may be

Insulin dependent/Insulin

independent.

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Types Of Glucose Transporters
GLUT-1 to GLUT-14 (Glucose

Transporter Isoforms) exist in the

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membranes of various body cells.

These Glucose transporters

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involved in Glucose uptake from

blood into specific tissues.

--- Content provided by FirstRanker.com ---

Type of GluT

Present on

Property

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Organs

Glu T1

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RBC `s, Brain, Retina, Insulin Independent

Placenta

GluT2

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Liver, Intestinal cells Insulin Independent

GluT3

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Neuron, Brain

Insulin Independent

GluT4

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Skeletal Muscles,

Insulin Dependent

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Heart, Adiposecytes

GluT5

Testis, Kidney,

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Poor ability for

Sperms

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Glucose and has good

uptake property for

Fructose.

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GluT7

Liver Endoplasmic

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Glucose transported

reticulum.

from E.R to cytosol.

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Sodium Dependent Glucose

Transporter -1 (SGluT-1)

Present in membranes of intestinal

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mucosal cells.

Helps in uptake of Glucose from

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intestinal lumen to intestinal mucosal

cells.

Defect in SGluT-1 leads to Glucose

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malabsorption.

Sodium Dependent

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Glucose Transporter -2

(SGluT-2)

Present in kidney tubules

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Defect in SGluT-2 leads to

Renal Glycosuria.
Inhibitors Of Glucose

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Transport

Glycosides :

Phlorizin

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(Inhibitor of Glucose Transporter-SGluT-1 of Intestine)
Ovabain

( Inhibitor of Na-K ATPase )

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They reduces blood Glucose.

Therapeutically used to control blood Glucose in

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Diabetes mellitus.
Locking Of Glucose Within The Cells

Free Glucose is permeable to cell

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membrane.

Glucose entered in cells is

phosphorylated to Glucose-6-

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Phosphate (Impermeable) and

locked within the cells.
Glucokinase in Liver

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Glucokinase in presence of ATP

and Mg++ ions Phosphorylates

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the Glucose to Glucose-6-

Phosphate when first enters the

hepatocytes.

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The Glucokinase is specific for

Glucose

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It has high Km value i.e low

affinity for Glucose for

phosphorylation reaction.

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As Glucokinase is slow in action

not all Glucose molecules entered

in hepatocytes are

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phosphorylated and locked.

The remained free form of Glucose

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come out of Liver and carried

through Systemic circulation.

Thus Glucose from

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systemic circulation

diffuses into extra hepatic

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tissues.
Hexokinase In

Extrahepatocytes

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The Glucose entered in extra

hepatocytes is phosphorylated to

Glucose-6-PO4 by an action of

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Hexokinase in presence of ATP and

Mg ++ ions.

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Hexokinase has low Km value

i.e very high affinity for Glucose

for phosphorylation reaction.

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Glucose is readily locked by

Hexokinase in extra hepatocytes

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at a very low Glucose

concentration.
Glucokinase

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Hexokinase

Phosphorylates Glucose to Glu- Phosphorylates Glucose to Glu-6-

6-Po4 in hepatocytes.

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Po4 in extra hepatocytes.

Glucokinase has high Km value Glucokinase has low Km value

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Glucokinase acts when Glucose Hexokinase acts when Glucose

concentration is high(> 100

concentration is low.(< 100 mg%)

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mg%)
Glucokinase is very specific

Hexokinase is not so specific acts

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acts only on Glucose.

on Glucose ,Fructose and Mannose.

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Glucokinase is dependent on

Hexokinase is not under influence

Insulin.

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of Insulin.

Glucokinase is not inhibited

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Hexokinase is inhibited by Glucose

by Glucose-6-PO4.

-6-PO4.

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Glucose import


Metabolic Fates Of Glucose

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Overview of Glucose Metabolism


Metabolic Pathways of Glucose

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In Well Fed Condition
In well fed condition Under the influence

of Insulin.

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Glucose-6-PO4 is metabolized as follows:

vFor Oxidation to produce chemical

form of energy ATP.

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vFor Storing Glucose.(Glycogen and

TAG)

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vFor production of Glucose derivatives

for metabolic use.

Complete Oxidation Of Glucose via (In all Cells)

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Glycolysis/EMP pathway
PDH complex reaction
TCA Cycle/Krebs Cycle

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Formation and Storage of Glycogen by

Glycogenesis (Liver and Muscles).

Alternative Glucose Oxidation

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HMP Shunt (NADPH+ H+ and Ribose)
Uronic Acid Pathway (Glucoronic acid)
Glucose is transformed to :
Lipids( Lipogenesis)

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? Fatty acids
? TAG
? Cholesterol

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Proteins building blocks.

qNon essential Amino acids.

Precursor for Lipogenesis is Acetyl ?CoA.

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Precursor for Amino acids is Pyruvate, OAA

Metabolic Pathways of Glucose

In Emergency Condition

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In emergency fasting condition when

blood Glucose lowers under influence

of Glucagon body tries to regulate the

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blood Glucose by stimulating:

Glycogenolysis
(Breakdown of Stored Glycogen)

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Gluconeogenesis
(Biosynthesis of Glucose).
Pattern to Study A

Metabolic Pathway

--- Content provided by‌ FirstRanker.com ---

? Synonyms/Different Names of Pathway.
? What is the Pathway ? (In brief)
? Where the pathway occurs?
(Organ/Cellular site)

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? When pathway occurs?
(well fed/emergency/aerobic/anaerobic)
? What type Of Pathway?
(Catabolic/Anabolic)
? How the pathway Occurs? (Type of Rxn,

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Enzymes ,Coenzymes)

? Why the Pathway occurred? (Significance)
? Precursor, intermediates, byproducts

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and end products of Pathway.

? Energetics of the pathway
(If Catabolic Pathway)

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? Interrelation ships with Other Pathways.
? Regulation of Pathway :Modes of

regulation.

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? Regulatory hormone/ Regulatory

Enzyme/Modulators.

? Inborn Error of the Metabolic Pathway

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Complete Oxidation Of Glucose
The main aim of Glucose in cells is to oxidize
(Remove Hydrogen) and catabolize to liberate energy.

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Glucose (C6) is completely oxidized to free CO2, H2O and

Energy (ATP). Glucose is completely oxidized via:

Glycolysis

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(1 Glucose 2 Pyruvate and ATP)
PDH Complex reaction
( 2Pyruvate 2 Acetyl-CoA and ATP)
TCA cycle
(2 Acetyl ?CoA CO2, H2O and ATP)

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GLYCOLYSIS
Synonyms Of Glycolysis

Embden Meyerhof Parnas (EMP)

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Pathway

Aerobic and Anerobic Oxidation Of

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Glucose.

Oxidation Of Glucose to Pyruvate.
Conversion of Glucose to Lactate.
What is Glycolysis?

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Major Oxidative Pathway of Glucose.
Takes place in cytosol of every cell of

human body.

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Glucose undergoes series of significant

catabolic reactions in aerobic and

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anaerobic conditions to form Pyruvate

and Lactate respectively.
Glucose(6C) 2Pyruvate + ATP

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(Aerobic Glycolysis) (3C)

Glucose 2 Lactate +ATP

(Anaerobic Glycolysis) (3C)

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Byproduct of Glycolysis is ATP.


Nature /Type Of Glycolysis

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Pathway
Glycolysis is a catabolic/ degradative

pathway.

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Oxidation of Glucose occurs in Glycolysis.
Removal of Hydrogen from Glucose

structure.

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Temporary acceptor of removed Hydrogen

is coenzyme NAD+ which get transformed

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to form reducing equivalent NADH+ H+.

Glycolysis-Energy Generating

Pathway

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The NADH+ H+

generated in the steps

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of Glycolysis enters

ETC for its reoxidation

and generation of ATP.

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When Glycolysis Occurs?

Glycolysis Occurs In

Cells when it needs energy .

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Aerobic/Anaerobic condition
(Uniqueness).
Well fed condition (Actively).
Erythrocytes needs continuous

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and uninterrupted Glycolysis

for their survival.

Where Glycolysis Occurs?

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Glycolysis

Occurs in

Cytoplasm of all

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body cells.

How Glycolysis Occurs?

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Glycolysis occurs in 10 steps.

Glycolysis is studied in
3 phases/3 stages:

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Phase I- Energy Utilizing Phase
Phase II- Splitting Phase
Phase III- Energy Generating Phase

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Enzyme Kinases
Involves ATP

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Require Mg ++

ions as cofactors.

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1. Phosphorylation Reaction
2. Isomerization Reaction
3. Phosphorylation Reaction
4. Lyase- Splitting Reaction
4 a. Isomerization Reaction.

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5. Oxidation and Phosphorylation Reaction
6. Substrate Level Phosphorylation Reaction
7. Mutase Reaction
8. Dehydration Reaction
9. Substrate Level Phosphorylation Reaction

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High Energy Compounds of

Glycolysis:

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1,3 Bis Phospho Glycerate.
Phospho Enol Pyruvate.
These high energy compounds

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have "high energy" bonds (~P) in

their structures.

Cleavage of these high energy

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bonds releases high energy .

Which is used for phosphorylation

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of ADP + pi and generation of ATP

at reaction/substrate level.

Thus a high energy

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compound in a

catabolic pathway is

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followed by a substrate

level Phosphorylation

reaction.

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Substrate Level

Phosphorylation Reaction

Is a mode of generation of

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ATP at substrate level after

the cleavage of high energy

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bond present in a high energy

substrate.

Glycolysis has 2 Substrate

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level phosphorylation

reactions.

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This mode of generation

of ATP at reaction level is a

quick/immediate mode.

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? 2Substrate Level Phosphorylating

Enzymes of Glycolysis :

?Phospho Glycerate Kinase

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?Pyruvate Kinase

Glycolysis has

3 irreversible reactions(1,3 and 9)

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(1 oxidation reaction)-2NADH+H+
2 high energy compounds.
2 substrate level phosphorylation

reactions. ( 4ATPs)

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3 Irreversible Enzymes of Glycolysis

vGlucokinase (GK)
vPhospho Fructo Kinase (PFK)
vPyruvate Kinase (PK )

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Byproducts/ Energetics Of

Glycolysis

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Reduced Coenzymes 2(NADH+H+) 5ATP
(1 NADH + H+ E.T.C 2.5 ATP)

2 ATP's each from two substrate level

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phosphorylation rxns.(4 ATP's).

9 ATP's ? 2 ATP's = 7 ATP's Net gain.
Enzyme Rxn Of Glycolysis

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Number of ATP

Utilized/Generated

Aerobic

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Anaerobic

Condition

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Condition

Glucokinase/Hexokinase

- 1 ATP

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- 1 ATP

Phosphofructokinase(PFK)

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- 1 ATP

- 1ATP

Glyceraldehyde-3-PO4

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2(NADH+H+ 2(NADH+H+

Dehydrogenase.

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enter ETC= do not enter ETC=
+5 ATP)

0ATP)

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Phosphoglycerate Kinase

+ 2ATP

+ 2 ATP

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Pyruvate Kinase

+ 2ATP

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+ 2 ATP

Net + 7ATP's.

Net + 2 ATP's.

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1 Glucose with Aerobic

Glycolysis 7 ATP's.

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1 Glucose with

Anaerobic Glycolysis

2 ATP's.

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Intermediates and end products

of Glycolysis serve as a

precursors for biosynthesis :

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Fatty acid

Cholesterol

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Amino acid

Regulation Of Glycolysis

Hormones regulating Glycolysis:

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INSULIN- Stimulates Glycolysis
(Well fed Condition)
GLUCAGON ? Inhibist Glycolysis
(Emergency Condition)
Regulatory / Key Enzymes of Glycolysis :

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3 Irreversible step catalyzing Enzymes:

v Glucokinase/Hexokinase
vPhospho Fructo Kinase ( PFK1) (IMP)

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vPyruvate Kinase ( PK )

Insulin and Glucagon

stimulate and inhibit

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Key/Regulatory

enzymes of Glycolysis

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respectively.
Al osteric Activators of PFK

AMP
Fructose-2,6 Bis Phosphate

--- Content provided by‌ FirstRanker.com ---

( Produced by PFK2 activity)
NAD+
Pi ( Inorganic Phosphorous )

Al osteric Inhibitors Of PFK

--- Content provided by FirstRanker.com ---

ATP
Citrate
NADH+ H+
H + ions ( Low pH /Acidosis)

--- Content provided by‌ FirstRanker.com ---

Feed Forward Regulation

Pyruvate Kinase is activated

by Fructose-1,6 bisphosphate

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formed by PFK1 activity.

This stimulates Glycolysis

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actively.

Inhibitors of Glycolysis

Fluoride Inhibits Enzyme

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Enolase of Glycolysis.

Arsenite ,Iodoacetate Inhibits

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Glyceraldehyde-3-PO4

Dehydrogenase.
Significance Of Glycolysis:

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Glycolysis is an unique pathway

operated in cytosol of each and

every cell to generate chemical

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form of energy

7 ATP (Aerobic Condition)
2 ATP (Anaerobic condition).

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In Aerobic conditions Glycolysis

provides energy (ATP) analogous to

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Cheque
(NADH+H+ enters Oxidative

phosphorylation /ETC) and

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Cash
(Substrate level Phosphorylation).
Intermediates of Glycolysis may serve

as precursor for non essential amino

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acids.

Pyruvate Transaminase Alanine

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Fates Of Pyruvate

In Aerobic

and

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Anaerobic Conditions
Pyruvate (3C )

keto acid is an end

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product of

Glycolysis.

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Fate Of Pyruvate In Aerobic

condition:

Pyruvate is oxidatively decarboxylated

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to Acetyl-CoA (2C) by the activity of

Pyruvate Dehydrogenase (PDH)

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complex.

A reducing equivalent NADH+H+ is

released at this reaction.

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Fate of Pyruvate in Anaerobic

Condition:

Pyruvate is reduced to Lactate by the

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activity of Lactate Dehydrogenase

(LDH) .

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NADH +H+ generated in Glycolysis and

not entering in ETC, in anaerobic

condition is utilized in the reduction

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of Pyruvate to Lactate.

Lactate is said

--- Content provided by​ FirstRanker.com ---

to be the dead

end Of the

Glycolysis.

--- Content provided by‌ FirstRanker.com ---

Significance of Pyruvate Reduction

To Lactate

Utilizes the Glycolytic generated

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NADH+H.

Does not accumulate the NADH+H+

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to inhibit PFK of Glycolysis.

Avoid interruption of Glycolysis and

continue it in anaerobic condition.

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Physiologically during

strenuous exercise.

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Muscle lacks enough oxygen.
Anaerobic Glycolysis forms

major source of energy to

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exercising muscles.
Lactate serves as a fuel source for

cardiac muscle as well as brain

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neurons .

Astrocytes, which surround and

protect neurons in the brain, ferment

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Glucose to Lactate and release it.

Lactate taken up by adjacent neurons

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is converted to Pyruvate that is

oxidized via Krebs Cycle.

Lactic acidosis is

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noted when there is

collapse in

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circulatory system.
Tissues in hypoxic condition

produces Lactate.

--- Content provided by​ FirstRanker.com ---

For ex in Ischemia, MI,

Embolism , Shock.

Lactate causes fatigueness of

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muscles.

Lacticacidosis is a

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condition of Metabolic

Acidosis where the

blood pH is lowered.

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Lacticacidosis detects Oxygen

Deficiency

Oxygen debt leads to interrupt

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Glycolysis.

Anaerobic Glycolysis.
Low/No production of ATP.

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Lacticacidosis.

Oxygen debt is related to patients

morbidity or mortality.

--- Content provided by FirstRanker.com ---

Measuring Lactate levels of blood

allows rapid and early detection of

--- Content provided by‌ FirstRanker.com ---

oxygen debt.

Correction of early Oxygen debt

helps in recovering the patients life.

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Inborn Error Of Glycolysis
Pyruvate Kinase

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deficiency in

Erythrocytes leads to

Hemolytic Anemia

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(Nonspherocytic

Hemolytic Anemia).

--- Content provided by‌ FirstRanker.com ---

PK deficiency

interrupts Glycolysis.

Interrupted Glycolysis

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affects the RBC's and

leads to its lysis.
Glycolysis in Cancer

--- Content provided by​ FirstRanker.com ---

In fast growing cancer cells Glycolysis

proceeds at a high rate forming large

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amounts of Pyruvate.

This Pyruvate is then reduced to

Lactate.

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This produces relatively acidic local

environment in tumor.

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Rapaport Leubering Cycle
Synonyms

2,3 Bis Phospho Glycerate

--- Content provided by⁠ FirstRanker.com ---

Cycle /(2,3BPG Cycle)

Shunt Glycolysis In

Erythrocytes

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Location/ Occurrence :

15-25% of Glucose

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enter via 2,3 BPG cycle

in the cytosol of

mature Erythrocytes.

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End Product of

Glycolysis in

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Erythrocytes is

Lactate.
Mature Erythrocytes has no

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Mitochondria.

Pyruvate obtained from

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Glycolysis could not be further

oxidized in Erythrocytes.

Pyruvate is reduced to Lactate

--- Content provided by⁠ FirstRanker.com ---

by LDH in Erythrocytes.

Salient Features Of

--- Content provided by‌ FirstRanker.com ---

Rapaport Leubering Cycle
In Rapaport Leubering cycle
A high energy compound 1,3 Bis

Phospho Glycerate is

--- Content provided by⁠ FirstRanker.com ---

transformed to a low energy

compound 2,3 Bis Phospho

--- Content provided by​ FirstRanker.com ---

Glycerate.

2,3 Bis Phospho Glycerate is

dephosphorylated to 3 Phospho

--- Content provided by FirstRanker.com ---

Glycerate and utilized.

This bypasses the substrate

--- Content provided by⁠ FirstRanker.com ---

level phosphorylation of

Glycolysis
Rapaport Leubering Cycle

--- Content provided by​ FirstRanker.com ---

generates no ATP.

It dissipiates/waste energy

as heat.

--- Content provided by‍ FirstRanker.com ---

It does not accumulate

ATP

--- Content provided by​ FirstRanker.com ---

Energetics Of Glycolysis In RBC's
Erythrocyte Glycolysis via 1,3 BPG

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2 ATP

Erythrocyte Glycolysis via 2,3 BPG

O ATP

--- Content provided by​ FirstRanker.com ---

Significance Of

Rapaport Leubering Cycle
Rapaport Leubering Cycle

--- Content provided by‍ FirstRanker.com ---

Maintains Glycolysis in

continuous and uninterrupted

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in RBC's.

This in turn maintains cellular

integrity of RBC's.

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Prevent hemolysis.

2,3BPG of Rapaport

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Leubering cycle in RBC's:

Has high affinity for

Hemoglobin.

--- Content provided by⁠ FirstRanker.com ---

Helps in unloading of

Oxygen by OxyHb at tissues.
2,3BPG Increases In

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? Hypoxic conditions

?High altitudes
?Fetal tissue

--- Content provided by‌ FirstRanker.com ---

?Anemic Condition

Inborn Error Of

Rapaport Leubering Cycle

--- Content provided by‌ FirstRanker.com ---

Hexokinase Pyruvate Kinase

Deficiency

Deficiency

--- Content provided by‍ FirstRanker.com ---

Decreases 2,3 BPG Increases 2,3 BPG

concentrations.

--- Content provided by⁠ FirstRanker.com ---

concentrations.

Decreases

Increases

--- Content provided by‍ FirstRanker.com ---

Unloading of

Unloading of

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Oxygen at tissues. Oxygen at tissues.

Pyruvate Metabolism

OR

--- Content provided by FirstRanker.com ---

Formation and Fates Of Pyruvate


GLUCOSE

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MALATE

ALAN

--- Content provided by FirstRanker.com ---

INE

--- Content provided by‍ FirstRanker.com ---

--- Content provided by​ FirstRanker.com ---

PYRUVATE



OXALOACETATE

--- Content provided by‌ FirstRanker.com ---

ACETYL-CoA

LACTATE
PYRUVATE IS FORMED FROM

--- Content provided by​ FirstRanker.com ---

Glucose (Glycolysis)
Lactate (Oxidation-LDH)
Malate (Malic enzyme)
Alanine (Transamination-ALT)

--- Content provided by⁠ FirstRanker.com ---

PVRUVATE IS CONVERTED TO

Glucose (Gluconeogenesis)
Lactate (Reduction-LDH)

--- Content provided by⁠ FirstRanker.com ---

Malate (Malic enzyme)
Alanine (Transamination-ALT)
Acetyl-CoA ( PDH Complex)
Oxaloacetate (Carboxylation

--- Content provided by‍ FirstRanker.com ---

Rxn)
Pyruvate Irreversibly forms

Acetyl-CoA

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Oxaloacetate

In Mitochondrial Matrix
These are the precursors

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of TCA cycle.

Oxidative Decarboxylation

Of

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Pyruvate To Acetyl-CoA

By

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Pyruvate Dehydrogenase (PDH)

Complex.
GLUCOSE

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TCA

CYCLE

Glycolysis

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NADH+H+

CO2

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NAD+

PYRUVATE

Acetyl-

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CoA

PDH

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Complex

Pyruvate is generated as an end

product of Glycolysis in the

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cytoplasm.

This is then transported into

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Mitochondrial matrix

By a Pyruvate transporter

located in the mitochondrial

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membrane.
Pyruvate, a 3 carbon keto acid
Obtained from Glycolysis is

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oxidized (removal of Hydrogen)

and decarboxylated (removal of

CO2)

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To form a 2 carbon, high energy

compound Acetyl-CoA and

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Reducing equivalent NADH+ H+.

Reducing equivalents

NADH+H+ released at this

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step enter in E.T.C for it's

reoxidation and generation

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of ATP's.

Thus this is an energy

producing step.

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Oxidative

Decarboxylation of

Pyruvate to Acetyl-CoA

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Is biocatalyzed by PDH

complex(Multi Enzyme

--- Content provided by‍ FirstRanker.com ---

Complex).

Acetyl-CoA formed

in PDH complex step,

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enters in TCA cycle

for its complete

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oxidation.
Thus PDH complex reaction

is a connecting reaction

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between Glycolysis and TCA

cycle.

PDH Complex

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Neuberg (1911) discovered PDH

complex.

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PDH Complex is a Multi Enzyme

complex.

PDH complex is composed of:

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3 Enzymes and 5 Coenzymes.
Three Enzymes Of PDH Complex:

vPyruvate Dehydrogenase
vDi Hydrolipoyl Dehydrogenase

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vDi Hydrolipoyl Transacetylase

? Five Coenzymes Of PDH Complex.

?TPP (Derived from Vit B1)

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?FAD (Derived from Vit B2)
?NAD+ (Derived from Vit B3)
?CoA-SH (Derived from Vit B5)
?Lipoic acid/Lipoamide.
Associated Enzymes and Coenzymes Of PDH

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Complex:

Pyruvate Dehydrogenase (E1)

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(Coenzyme = TPP)

Dihydrolipoamide Acetyltransferase (E2)

(Coenzymes = Lipoamide, CoA)

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Dihydrolipoamide Dehydrogenase (E3)

(Coenzymes = FAD, NAD+)

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Location Of PDH complex:

PDH complex is

located in

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Mitochondrial matrix.
Reaction biocatalyzed by

PDH Complex is

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completely an irreversible

reaction.

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Due to irreversible nature of PDH

complex reaction:

Acetyl-coA obtained through

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oxidation of Fatty acids

cannot be converted to Pyruvate

and used for Glucose production.

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Thus Fat is not converted to

Carbohydrates in human body.
Working Of PDH Complex

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PDH Complex irreversibly

biocatalyzes

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An Oxidative Decarboxylation

of Pyruvate to Acetyl-coA

At aerobic conditions in

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mitochondrial matrix.

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Regulation Of PDH Complex

PDH Complex is

stimulated by INSULIN.

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PDH Complex is inhibited

by GLUCAGON.

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Activators Of PDH Complex.

ADP
NAD+
Inhibitors Of PDH Complex

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ATP
NADH+ H+
Cyclic AMP
Acetyl-CoA

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Chemical Inhibitors Of PDH

Complex

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Arsenic
Mercuric Ions
Deficiency Of

PDH Complex

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And Its

Consequences

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PDH Complex deficiency is rare
It blocks the conversion of Pyruvate to

Acetyl-CoA

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Brings incomplete Oxidation Of Glucose
Increases Pyruvate concentration
Increased Pyruvate is reduced to Lactate
Leads to Lactic acidosis
Decreases Acetyl ?CoA, which Decreases TCA

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cycle

Decreases ATP level
Low ATP levels affects cellular activities.

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Fatigue ,Weakness, Neurological Disorders.
TCA CYCLE

Synonyms OF TCA Cycle
Fate of Acetyl CoA

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Tri Carboxylic Acid Cycle (TCA Cycle)
Citric Acid Cycle
Krebs Cycle (Hans Kreb-1937)
Amphibolic Pathway
Common Metabolic Pathway

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Central Metabolic Pathway
Final Oxidative Pathway

What Is TCA Cycle?
Common metabolite Acetyl-CoA

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Obtained from Glucose, Fatty

acids and Amino acid metabolism

Finally , commonly and

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completely oxidized via TCA cycle.

1 Acetyl-CoA +3NAD+ + FAD + GDP + Pi

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Over all TCA

2 CO2+CoA + 3NADH +3H++ 1FADH2 + 1GTP
Acetyl-CoA a central/common

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metabolite is completely oxidized

To liberate 2CO2, and reducing

equivalents 3NADH+H+ , 1 FADH2

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and 1GTP through TCA cycle.

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10 ATPs generated on

oxidation of

1 Acetyl CoA via TCA

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cycle
Nature/Type Of Pathway

TCA is an Amphibolic

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Pathway.

It is connected to both

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Amphibolic and

Catabolic Pathway.
Condition In which Pathway Occurs

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TCA is purely

carried out in an

Aerobic condition.

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Location : Organ and Cellular Site

TCA is carried out in all

cells which contain

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Mitochondria.

Cellular site for TCA is

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Mitochondrial Matrix.
TCA cycle des not

operate in

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Mature Erythrocytes

,Cornea and Lens cells

Since they are devoid of

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Mitochondria.

Reactions Steps OF TCA Cycle:
TCA cycle

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constitutes 10 steps.

Acteyl?CoA and

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Oxaloacetate(OAA)

are initators of

TCA cycle.

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Sources Of Acetyl CoA

Glucose Metabolism
(PDH Complex Reaction)
Fatty Acid Metabolism

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( Oxidation of Fatty acids)
Amino Acid Metabolism

Sources Of Oxaloacetate(OAA)
OAA used in TCA is majorly

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obtained from Glucose

metabolism

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(In a well fed condition )
OAA comes minorly from

Amino acid (ASP)

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[In an emergency condition].

Oxaloacetate is a 4 Carbon Keto acid

obtained from Pyruvate a 3 Carbon Keto

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acid on Carboxylation reaction.

Pyruvate is carboxylated to Oxaloactate

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by an irreversible activity of an enzyme

Pyruvate Carboxylase, ATP and

Coenzyme Biotin.

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In TCA cycle Oxaloacetate used

up in first step is regenerated in

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last step.

2 carbon units lost in TCA cycle in

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the form of CO2 is from OAA .

The regenerated OAA gets 2

Carbon atoms from entered 2

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carbon Acetyl-CoA.
TCA Is An Amphibolic Pathway

Catabolic Role Of TCA Cycle

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TCA is associated to Carbohydrates

,Lipids, and Proteins for its complete

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metabolism.

65-70% of ATP is generated through

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TCA cycle.

TCA is a most energetic metabolic

pathway.

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1. Aldol Condensation
2. Isomerization- Dehydration and Rehydration
3. Oxidation

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4. Decarboxylation
5. Oxidative Decarboxylation
6. Substrate Level Phosphorylation
7. Oxidation
8. Hydration

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9. Oxidation
Central metabolite Acetyl-CoA obtained

from Glucose, Fatty acids, and Amino acid

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metabolism.

Acetyl-CoA enters in TCA cycle and

completely oxidized to free CO2 and

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reducing equivalents which further enters

ETC to generate ATPs.

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Since Acetyl-CoA is catabolized and

produces energy.

Thus TCA has catabolic and energy

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generating role.

Succinate Dehydrogenase is the

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only enzyme of TCA embedded in

the inner mitochondrial

membrane.

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Succinate Dehydrogenase

functions as Complex II of ETC.
Alpha KDH Complex Is a

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Multi Enzyme Complex

3 Enzymes

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Alpha Keto Glutarate

Dehydrogenase

Dihydrolipoyl

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Dehydrogenase

Dihydrolipoyl Trans

--- Content provided by‍ FirstRanker.com ---

Succinylase
5 Coenzymes

TPP
FAD

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NAD+
Lipoamide
CoA

Anabolic Role Of TCA

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Citric acid cycle intermediates are

always in flux

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In TCA Cycle there is

continuous influx and efflux of

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intermediate metabolites as per

cellular need.

TCA is considered as a

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metabolic Traffic Circle.
Various intermediates of TCA

cycle are connected to the

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biosynthesis of various

functional biomolecules of

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human body.

This role of TCA signifies

Anabolic role .

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Citrate a 6 carbon moiety is a

first Tricarboxylic acid

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produced in TCA.

Citrate is a carrier of acetate

carbons for De novo

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biosynthesis of Fatty acids in

cytosol.
Acetyl CoA obtained

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from Glucose in a well

fed condition is a

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precursor of fatty acid

biosynthesis.

Acetyl ?CoA is impermeable

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to mitochondrial membrane.

Impermeable Acetyl-CoA of

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mitochondria is brought out in

the cytosol in a permeable

form of Citrate.

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Citrate in cytosol

undergo lysis by Citrate

Lyase to regenerate

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Acetyl-CoA and OAA.

Alpha Keto Glutarate ( KG) a 5

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carbon Keto acid, an intermediate

of TCA is involved in

Transamination reaction of

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Aminoacids.

KG is an acceptor of an amino

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group from another amino acid

involved in Transamination

reaction.

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KG on Transamination forms its

corresponding amino acid

Glutamic acid.

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Thus KG is a precursor for

biosynthesis of non essential

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amino acid in human body.

Oxaloacetate of TCA is also

transaminated to a non essential

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amino acid Aspartate.

Intermediates of TCA are

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Glucogenic precursors

In an emergency conditions they

are used for biosynthesis of

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Glucose.
Succinyl ?CoA, a high energy

compound ,an intermediate of TCA

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cycle is followed by Substrate level

Phosphorylation reaction to generate

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GTP at reaction level.

Succinyl-CoA is a precursor for Heme

biosynthesis .

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Succinyl-CoA is involved in Ketolysis

where it is a CoA donor for

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Thiophorase reaction.

Intermediates of TCA cycle are

connected to Biosynthesis of

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Lipids
(Lipogenesis )
Glucose
(Gluconeogenesis)

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Aminoacids
(Nutritionally Nonessential)
TCA cycle is termed as

open cycle- Since an

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intermediates of TCA

cycle enter and leave the

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cycle as per the cellular

need.

TCA Cycle is analogus/

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Illustrated as- "Heavy Traffic

Circle" in a National

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Highway with many

connecting roads.

Since many intermediates of

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TCA cycle are interconnected

to other metabolic pathways.
TCA Cycle provides

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intermediates for many

biosynthetic processes

--- Content provided by‌ FirstRanker.com ---

Energetics Of Per Turn TCA Cycle
Enzymes Generating Reducing

Equivalents

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Isocitrate Dehydrogenase -------------NADH+H+

Ketoglutarate Dehydrogenase -------NADH+H+

Malate Dehydrogenase------------------NADH+H+

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Succinate Dehydrogenase --------------FADH2

Succinate Thiokinase --------------------GTP

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In per turn of TCA cycle 1 Acetyl-

CoA enters to catabolize and

generate 3NADH+ H+ 1 FADH2

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and 1 GTP.
3 NADH+ H+ when enters ETC it generates

7.5 ATPs

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1 FADH2 when enters ETC generates 1.5

ATPs.

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1 Substrate level phosphorylation generates

1 GTP.

Net 10 ATP's are generated per turn of TCA

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cycle.

Significance of TCA

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TCA Cycle is the

largest generator of

ATP among the

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metabolic pathways.
Reduced Coenzymes Fuel ATP

Production

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Isocitrate Dehydrogenase

1 NADH=2.5

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ATP

a- Ketoglutarate Dehydrogenase

1 NADH=2.5

--- Content provided by FirstRanker.com ---

ATP

Succinate Thiokinase

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1 GTP=1 ATP

Succinate Dehydrogenase

1 FADH2=1.5 ATP

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Malate Dehydrogenase

1 NADH=2.5

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ATP

Total of 10 ATPs gained from oxidation of 1

Acetyl-CoA per TCA turn.

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GTP formed in TCA cycle is

used in following step of

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Gluconeogenesis:

Conversion of Oxaloacetate

to PhosphoenolPyruvate

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(PEP) in presence of enzyme

PEP Carboxykinase and GTP.
Regulation Of TCA Cycle

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Hormone Insulin in well fed condition

stimulates and activates key / regulatory

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Enzymes of TCA cycle.

Key Enzymes of TCA cycle :
Citrate Synthase
Isocitrate Dehydrogenase (IDH)

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Keto Glutarate Dehydrogenase

(KDH)

Activators of key Enzymes-

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ADP,AMP

Inhibitors Of key Enzymes-

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ATP, NADH+ H+, Succinyl-CoA
Citrate of TCA inhibits PFK of

Glycolysis.

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Citrate stimulate Fructose -1,6

Bisphosphatase of

Gluconeogenesis.

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Citrate activates Acetyl CoA

Carboxylase of Fatty acid

--- Content provided by‌ FirstRanker.com ---

biosynthesis.

Regulation Of TCA by availability of ADP:

Low levels of ADP in cells indirectly inhibit

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TCA cycle.

ADP is required for synthesis of ATP through

--- Content provided by‌ FirstRanker.com ---

oxidative phosphorylation (ETC).

Low/Limited ADP are insufficient to reoxidize

reducing equivalents NADH+ H+ ,FADH2

--- Content provided by‌ FirstRanker.com ---

generated during TCA.

This accumulates NADH+ H+ ,FADH2 which

--- Content provided by‌ FirstRanker.com ---

are inhibitors of key enzymes of TCA cycle.
Chemical Inhibitors OF TCA cycle

INHIBITOR

--- Content provided by‍ FirstRanker.com ---

ENZYME INHIBITED

and Type
Fluoroacetate Aconitase

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(Non Competitive)
Arsenite

Keto Glutarate

--- Content provided by‌ FirstRanker.com ---

(Non Competitive) Dehydrogenase.

Malonate

Succinate

--- Content provided by​ FirstRanker.com ---

(Competitive)

Dehydrogenase

--- Content provided by FirstRanker.com ---

TCA enzyme defects

has reported to suffer

from severe

--- Content provided by‍ FirstRanker.com ---

neurological damage

due to impaired ATP

--- Content provided by⁠ FirstRanker.com ---

formation in CNS.
Hyperammonaemia Impairs TCA

High ammonia levels in blood are

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toxic to body since they deplete

the levels of -Keto Glutarate.

(an intermediate of TCA cycle)

--- Content provided by FirstRanker.com ---

Low levels -Keto Glutarate, affects

the operation of TCA cycle and

production of ATPs.

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Vitamin B Complex deficiencies affects

Glucose metabolism and has low ATP

--- Content provided by⁠ FirstRanker.com ---

production.

Vitamin B complex members are

modified to Coenzymes required in

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enzyme catalysis of metabolic reactions.

One should take care to supplement

--- Content provided by‍ FirstRanker.com ---

adequate Vitamin B complex through

ingestion of fresh fruits and vegetables.
Beri Beri and
Wernicke Korsakoff Syndome ( In

--- Content provided by‍ FirstRanker.com ---

alcoholics)

Due to Thiamine (TPP) deficiency.
TPP is a member of multienzyme

--- Content provided by‌ FirstRanker.com ---

complex PDH and Alpha KDH.

Low TPP= low ATP
Low Nervous tissue , Cardiac Functions.

--- Content provided by FirstRanker.com ---

Pellegra is due to Niacin deficiency.
Niacin deficiency affects the

concentration of coenzymes NAD+

--- Content provided by FirstRanker.com ---

and NADP.

NAD+ and NADP deficiency affects

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metabolism by low ATP

production.
Leigh Syndrome

--- Content provided by FirstRanker.com ---

Leigh Syndrome is a rare disorder
Also referred as Sub acute Necrotizing

Encephalomyelopathy

--- Content provided by‌ FirstRanker.com ---

Progressive neurological disorder
Defect in mitochondrial ATP production
Mutations in PDH Complex/ATP Synthase of

ETC.

--- Content provided by‍ FirstRanker.com ---

Anaplerotic Reactions/

Anaplerosis
Anabolic reactions connected

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to TCA cycle utilizes the

intermediates of this cycle.

--- Content provided by⁠ FirstRanker.com ---

The drawn up intermediates

should be replenished.

If not replenished ,TCA cycle

--- Content provided by⁠ FirstRanker.com ---

will stop to operate.

The biochemical

--- Content provided by​ FirstRanker.com ---

reactions which replenish

or add up/fill up the

intermediates of TCA

--- Content provided by‍ FirstRanker.com ---

cycle and maintain its

operation are termed as

--- Content provided by​ FirstRanker.com ---

anaplerotic reactions.
The Anaplerotic Reactions

The "filling up" reactions

--- Content provided by‍ FirstRanker.com ---

? PEP Carboxylase - converts PEP

to Oxaloacetate

? Pyruvate Carboxylase - converts

--- Content provided by‍ FirstRanker.com ---

Pyruvate to Oxaloacetate

? Malic enzyme converts Pyruvate

--- Content provided by​ FirstRanker.com ---

into Malate

Anaplerotic Reactions

Pyruvate Pyruvate Carboxylase Oxaloacetate

--- Content provided by FirstRanker.com ---

CO2 ATP ADP Biotin

Pyruvate Malic Enzyme Malate
NADP NADPH+H+

--- Content provided by‌ FirstRanker.com ---

Glutamate

GDH

Keto Glutarate

--- Content provided by‍ FirstRanker.com ---

Aspartate AST Oxaloacetate
Energetics Of Complete Oxidation

of Glucose

--- Content provided by⁠ FirstRanker.com ---

1 molecule of

Glucose on

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complete oxidation

in body cells

--- Content provided by​ FirstRanker.com ---

liberate 32 ATP's.
Glycogen Metabolism

Glycogenesis

--- Content provided by‌ FirstRanker.com ---

And

Glycogenolysis
GLYCOGENESIS

--- Content provided by‌ FirstRanker.com ---

GLYCOGENOLYSIS

Glycogenesis is biosynthesis Glycogenolysis is

of Glycogen from free and

--- Content provided by FirstRanker.com ---

breakdown of Glycogen to

excess of Glucose in well fed Glucose in emergency

--- Content provided by FirstRanker.com ---

condition in the cytoplasm condition in the Liver and

of Liver and Muscles.

Muscles.

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Glycogenesis is an anabolic Glycogenolysis is a catabolic

process to store free excess degradative process to

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Glucose in the form of

utilize the stored Glycogen

condensed , compact,

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after its cleavage to release

globular, and granular form Glucose ,which on further

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as ?Glycogen.

oxidation generate ATPs in

emergency conditions.

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Where Glycogen Metabolism

Occurs?
Site/Location Of Glycogen

--- Content provided by​ FirstRanker.com ---

Metabolism

Organs for Glycogen Metabolism:

--- Content provided by‌ FirstRanker.com ---

Liver and Muscles.
Cellular Site :

Cytoplasm

--- Content provided by FirstRanker.com ---

In Liver

Rate of Glycogen Synthesis- 6-8%
Amount Stored- 75-150 gm.

--- Content provided by‍ FirstRanker.com ---

In Muscles

Rate of Glycogen Synthesis- 1-2 %
Amount Stored- 250-400 gm.
1% of Glycogen

--- Content provided by​ FirstRanker.com ---

stored in

cardiac/heart

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muscles.

Storage of

Glycogen in

--- Content provided by‌ FirstRanker.com ---

tissues is limited.
When Glycogenesis Operated?

Glycogenesis takes place after a

--- Content provided by​ FirstRanker.com ---

well fed condition.

After a heavy Carbohydrate

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meals.

When there is free and excess

of cellular Glucose.

--- Content provided by FirstRanker.com ---

Under the influence of Insulin.
How Glycogenesis Occur?

Steps Of Glycogenesis

--- Content provided by FirstRanker.com ---

Process of

Glycogenesis

--- Content provided by‍ FirstRanker.com ---

involves

following Steps:
Activation of

--- Content provided by‌ FirstRanker.com ---

Glucose to

UDP-Glucose.
(Energetic Compound)

--- Content provided by‍ FirstRanker.com ---

Glycogen synthesis

depends on sugar

--- Content provided by⁠ FirstRanker.com ---

nucleotides

UDP-Glucose
Glycogenesis Needs

--- Content provided by​ FirstRanker.com ---

Glycogen Primer

A Glycogen Primer

is required to

--- Content provided by‌ FirstRanker.com ---

initate the process

of Glycogenesis
Glycogen Primer

--- Content provided by‌ FirstRanker.com ---

at a very first time

of Glycogenesis in

--- Content provided by​ FirstRanker.com ---

a body is a Protein

Glycogenin.

Glycogenin

--- Content provided by⁠ FirstRanker.com ---

catalyzes primer

formation.
Glycogenin is a protein

--- Content provided by‍ FirstRanker.com ---

scaffold on which Glycogen

molecule is built.

--- Content provided by FirstRanker.com ---

? First Glucose is linked to a

Tyrosine ?OH of Glycogenin.

Glycogenin by

--- Content provided by FirstRanker.com ---

auto glucosylation

using UDP-Glucose

--- Content provided by​ FirstRanker.com ---

form a Glycogen

primer.
Glycogen primer in

--- Content provided by​ FirstRanker.com ---

an adult body:

Is a residual of

Glycogen molecule left

--- Content provided by‌ FirstRanker.com ---

out after

Glycogenolysis in

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tissues.

Glycogen Synthase

? Glycogen Synthase is the main

--- Content provided by‌ FirstRanker.com ---

enzyme of Glycogenesis.

? It forms -(1 4) glycosidic bonds in

--- Content provided by⁠ FirstRanker.com ---

Glycogen.

? Glycogen Synthase requires 4 to 8

Glucose units on Glycogenin for its

--- Content provided by⁠ FirstRanker.com ---

activity.
UDP- Glucose is linked

to non reducing ends of

--- Content provided by​ FirstRanker.com ---

Glycogen Primer by

Glycogen Synthase

--- Content provided by​ FirstRanker.com ---

activity to grow the linear

chain.

Glycogen Synthase

--- Content provided by‍ FirstRanker.com ---

transfers Glucosyl units

from UDP-Glucose to C-4

--- Content provided by‌ FirstRanker.com ---

hydroxyl at a nonreducing

end of a Glycogen

strand/Glycogen primer.

--- Content provided by‌ FirstRanker.com ---

After stipulated

growth of linear chain,

Branching enzyme

--- Content provided by⁠ FirstRanker.com ---

adds a branching

point.

--- Content provided by⁠ FirstRanker.com ---

Alternate activities of

Glycogen Synthase and

Branching Enzyme occurs

--- Content provided by‍ FirstRanker.com ---

To link UDP-Glucose units to

form a complex, compact and

--- Content provided by‌ FirstRanker.com ---

condensed structure of

Glycogen.

--- Content provided by⁠ FirstRanker.com ---

During Glycogenesis.

Glycogen Synthase -builds (1-4)

glycosidic bonds.

--- Content provided by​ FirstRanker.com ---

Branching Enzyme ? Glucosyl
(4-6) Transferase builds (1-6)

glycosidic bonds.

--- Content provided by‍ FirstRanker.com ---

More branching points in a

Glycogen molecule

Increases the number of non

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reducing ends

Which can be elongated by

--- Content provided by​ FirstRanker.com ---

addition of new Glucose residues to

it

By Glycogen Synthase activity.

--- Content provided by⁠ FirstRanker.com ---

UDP released during

Glycogenesis is

--- Content provided by‌ FirstRanker.com ---

converted to UTP at

an expense of ATP.
Significance Of Glycogenesis

--- Content provided by‌ FirstRanker.com ---

Glycogenesis stores free

and excess Glucose in

condensed, compact and

--- Content provided by‌ FirstRanker.com ---

granular form which:

Reduces osmotic effect
Occupy less space.

--- Content provided by​ FirstRanker.com ---

Glycogenolysis

Site Of Glycogenolysis

Cytoplasm of Liver and

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Muscles.

Where Granules of

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Glycogen stored.
When Glycogenolysis Occur?

Glycogenolysis occur in the body

--- Content provided by‌ FirstRanker.com ---

when:

Stored Glycogen needs to be

utilized.

--- Content provided by​ FirstRanker.com ---

Blood or cellular Glucose lowers.
There is fasting or starvation.
There are long hours between

--- Content provided by‌ FirstRanker.com ---

meals.
Steps Of Glycogenolysis

Glycogenolysis is not a

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just reversal of

Glycogenesis.

A different sets of

--- Content provided by‍ FirstRanker.com ---

enzyme used.


Glycogenolysis involves

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cleavage of (1-4) and (1-6)

glycosidic bonds of Glycogen.

--- Content provided by‌ FirstRanker.com ---

Enzyme Glycogen

Phosphorylase cleaves (1-4)

glycosidic bonds.

--- Content provided by‍ FirstRanker.com ---

Debranching Enzymes

removes (1-6) glycosidic bonds.
? Glycogen Phosphorylase is a

--- Content provided by‍ FirstRanker.com ---

main enzyme of

Glycogenolysis.

--- Content provided by‌ FirstRanker.com ---

? Glycogen Phosphorylase

cleaves Glycogen at non-

reducing end to generate

--- Content provided by‌ FirstRanker.com ---

Glucose-1-phosphate

? Glycogen Phosphorylase cleaves (1

--- Content provided by‌ FirstRanker.com ---

-4) glycosidic bonds linking

Glucose from the non reducing

ends of glycogen molecules

--- Content provided by⁠ FirstRanker.com ---

? This is a Phosphorolysis, not a

hydrolysis

--- Content provided by FirstRanker.com ---

? Metabolic advantage: product is a

sugar-P - a "sort-of" Glycolysis

substrate

--- Content provided by‍ FirstRanker.com ---

End Products Of Glycogenolysis
During Glycogenolysis

--- Content provided by​ FirstRanker.com ---

Enzyme Glycogen

Phosphorylase by its

activity releases

--- Content provided by​ FirstRanker.com ---

Glucose -1-PO4.

Debranching by

--- Content provided by FirstRanker.com ---

bifunctional (two) Enzymes.

Glucosyl (4 , 4) Transferase.
Amylo (1-6) Glucosidase
Debranching Enzyme

--- Content provided by​ FirstRanker.com ---

Amylo (1-6) Glucosidase

Acts on exposed

--- Content provided by⁠ FirstRanker.com ---

branching point (1-6)bond

of Glycogen and releases

free Glucose.

--- Content provided by​ FirstRanker.com ---

The number of free Glucose

units released during

--- Content provided by​ FirstRanker.com ---

Glycogenolysis depends upon

The number of branching

points hydrolyzed by

--- Content provided by‍ FirstRanker.com ---

Debranching enzyme activity.
Glucose-1-PO4 : Free Glucose

8: 1

--- Content provided by⁠ FirstRanker.com ---

Released during Glycogenolysis

Muscle Glycogenolysis Liver Glycogenolysis
In Muscles Enzyme Glucose- In Liver Enzyme Glucose-6-

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6-Phosphatase is naturally Phosphatase is naturally

absent.

--- Content provided by​ FirstRanker.com ---

present.

Glucose-6-PO4 ends as an

In Liver Glucose-6-PO4 of

--- Content provided by​ FirstRanker.com ---

end product of

Glycogenolysis is

--- Content provided by‌ FirstRanker.com ---

Glycogenolysis which further transformed to free Glucose

enters Glycolysis and get

(permeable) by Glucose-6-

--- Content provided by⁠ FirstRanker.com ---

metabolized within muscle

Phosphatase activity.

--- Content provided by​ FirstRanker.com ---

cells.

Muscle Glycogenolysis has

Free Glucose formed from

--- Content provided by​ FirstRanker.com ---

no role in blood Glucose

Liver Glycogenolysis comes

--- Content provided by FirstRanker.com ---

regulation

out in blood and helps in

blood Glucose regulation.

--- Content provided by⁠ FirstRanker.com ---

Significance Of Glycogenolysis

Muscle Glycogen is

extensively degraded in

--- Content provided by‌ FirstRanker.com ---

exercising muscles to

provide energy for it's

--- Content provided by​ FirstRanker.com ---

activity.
Liver Glycogenolysis operates to
Generate free Glucose from breakdown of

stored Glycogen.

--- Content provided by‌ FirstRanker.com ---

Liver Glycogenolysis add free Glucose to blood.
Regulates blood glucose levels.
Correct fasting Hypoglycemia
Supply sufficient Glucose to Brain and

--- Content provided by​ FirstRanker.com ---

Erythrocytes.

Try to maintain good function of brain and

--- Content provided by⁠ FirstRanker.com ---

RBC's in fasting condition

Stored Glycogen in

Liver on Glycogenolysis

--- Content provided by‍ FirstRanker.com ---

,supply Glucose in a

rapid and mobilizable

--- Content provided by‍ FirstRanker.com ---

form.
Liver Glycogenolysis

regulates blood

--- Content provided by‍ FirstRanker.com ---

Glucose levels in

early stages of fast.

Liver

--- Content provided by⁠ FirstRanker.com ---

Glycogenolysis

corrects fasting

--- Content provided by‌ FirstRanker.com ---

Hypoglycemia.
Regulation OF

Glycogen Metabolism

--- Content provided by​ FirstRanker.com ---

Regulation means good coordination of

Glycogenesis and Glycogenolysis as an

when required by the body to maintain

--- Content provided by FirstRanker.com ---

blood Glucose in normal range.

Glycogen metabolism is regulated by

--- Content provided by⁠ FirstRanker.com ---

stimulation or inhibition of

regulatory/key enzymes of Glycogen

metabolism under hormonal influence.

--- Content provided by​ FirstRanker.com ---

Glycogenesis and

Glycogenolysis are

reciprocally regulated

--- Content provided by​ FirstRanker.com ---

In well fed condition

Glycogenesis is onn
Glycogenolysis is off

--- Content provided by FirstRanker.com ---

In fasting condition

Glycogenolysis is onn
Glycogenesis is off

--- Content provided by​ FirstRanker.com ---

Modes Of Regulation

Hormonal Regulation
(Covalent Modification Of Key Enzymes

--- Content provided by‌ FirstRanker.com ---

of Glycogen Metabolism)

Allosteric regulation
Influence Of Calcium on

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Glycogen Metabolism.

Hormonal Regulation

Insulin In well fed condition

--- Content provided by‌ FirstRanker.com ---

Stimulates Glycogenesis
Inhibits Glycogenolysis
Glucagon and Epinephrine In

--- Content provided by⁠ FirstRanker.com ---

emergency condition :

Stimulates Glycogenolysis
Inhibits Glycogenesis

--- Content provided by‌ FirstRanker.com ---

Glucagon and Epinephrine
Acts via second messenger

cyclic AMP by cascade of

--- Content provided by​ FirstRanker.com ---

reactions

Regulates the enzymes and

pathway of Glycogen

--- Content provided by​ FirstRanker.com ---

metabolism.
Glucagon has no effect

on Muscle Glycogenolysis.

--- Content provided by FirstRanker.com ---

Epinephrine and Calcium

stimulates Muscle

--- Content provided by‌ FirstRanker.com ---

Glycogenolysis.

Regulatory Enzyme Of Glycogenesis:

Glycogen Synthase

--- Content provided by‍ FirstRanker.com ---

Regulatory Enzyme Of Glycogenolysis:

Glycogen Phosphorylase.

--- Content provided by‌ FirstRanker.com ---

Covalent Modification Of Enzymes

Glycogen

--- Content provided by‍ FirstRanker.com ---

Glycogen

Phosphorylase

Synthase

--- Content provided by⁠ FirstRanker.com ---

v "A" Form Active Form

"A" Form Active Form

--- Content provided by​ FirstRanker.com ---

Phosphorylated Form

Dephosphorylated Form

v"B" Form Inactive Form

--- Content provided by‍ FirstRanker.com ---

"B" Form Inactive Form

Dephosphorylated Form

--- Content provided by​ FirstRanker.com ---

Phosphorylated Form

--- Content provided by⁠ FirstRanker.com ---

Effect of glucagon and epinephrine on glycogen

phosphorylase glycogen synthase activities

--- Content provided by‍ FirstRanker.com ---

Effect of Insulin on Glycogen Phosphorylase

Glycogen Synthase activities

--- Content provided by FirstRanker.com ---

Influence of Calcium in Regulation

of Glycogen metabolism.
Calcium stimulates Liver

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and muscle Glycogenolysis

Calcium inhibits Liver and

muscle Glycogenesis.

--- Content provided by‍ FirstRanker.com ---

Calcium binds to

Calmodulin, which then

--- Content provided by​ FirstRanker.com ---

activates an enzyme muscle

Phosphorylase Kinase b

and Liver Phosphorylase

--- Content provided by‍ FirstRanker.com ---

Kinase b.
Calcium activated

Phosphorylase Kinase

--- Content provided by‌ FirstRanker.com ---

b stimulates and

activates Glycogen

--- Content provided by⁠ FirstRanker.com ---

Phosphorylase.

Thus Calcium indirectly

activates Glycogen

--- Content provided by‌ FirstRanker.com ---

Phosphorylase

Calcium Stimulates

--- Content provided by FirstRanker.com ---

Glycogenolysis.


Glycogen Storage Disorders

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OR

Inborn Errors Of Glycogen

Metabolism

--- Content provided by⁠ FirstRanker.com ---

Glycogen Storage Disorders

are inherited/congenital

metabolic defects concerned

--- Content provided by​ FirstRanker.com ---

with Glycogenesis and

Glycogenolysis.

--- Content provided by​ FirstRanker.com ---

Cause:
Enzyme defects of Glycogen

metabolism.

--- Content provided by‌ FirstRanker.com ---

Type:
Generalized/Tissue specific
Consequences of Glycogen Storage

Disorders:

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Abnormal form or amount of

Glycogen is deposited in Muscles ,Liver

--- Content provided by‍ FirstRanker.com ---

or both.

Affects the functional activities of

these tissues.

--- Content provided by⁠ FirstRanker.com ---

No correction of fasting hypoglycemia.
No supply of energy to muscles during

emergency conditions.

--- Content provided by​ FirstRanker.com ---

Types Of Glycogen Storage

Disorders
Type of Glycogen Name of Glycogen

--- Content provided by‌ FirstRanker.com ---

Enzyme Defect

Storage Disorder

--- Content provided by FirstRanker.com ---

Storage Disorder

Type I

Von Gierke's Disease

--- Content provided by​ FirstRanker.com ---

Liver Glucose-6-

Phosphatase

--- Content provided by‌ FirstRanker.com ---

Type II

Pompe's Disease

Lysosomal (1-4)

--- Content provided by FirstRanker.com ---

Glucosidase

Type III

--- Content provided by‍ FirstRanker.com ---

Cori's Disease

Debranching Enzyme

Type IV

--- Content provided by FirstRanker.com ---

Anderson's Disease

Branching Enzyme

--- Content provided by‌ FirstRanker.com ---

Type V

Macrdle's Disease

Muscle Glycogen

--- Content provided by⁠ FirstRanker.com ---

Phosphorylase

Type VI

--- Content provided by‍ FirstRanker.com ---

Her's Disease

Hepatic Glycogen

Phosphorylase

--- Content provided by‍ FirstRanker.com ---

Lewi's Disease

Glycogen Synthase

--- Content provided by FirstRanker.com ---

Type VII

Tauri's Disease

Phospho Fructo

--- Content provided by‌ FirstRanker.com ---

Kinase

Disorders Related to Glycogenesis
Lewis Disease Glycogen Synthase

--- Content provided by FirstRanker.com ---

Deficiency

Andersons

--- Content provided by FirstRanker.com ---

Branching Enzyme

Disease

Glucosyl (4-6)

--- Content provided by⁠ FirstRanker.com ---

Transferase

deficiency.

--- Content provided by‌ FirstRanker.com ---

Disorders Related to Glycogenolysis


Von Gierkes Disease

--- Content provided by⁠ FirstRanker.com ---

Enzyme Defect:

qLiver Glucose-6-Phosphatase deficiency

Biochemical Alterations and Manifestations:

--- Content provided by FirstRanker.com ---

vHypoglycemia
vHyperlipidemia
vHyperuricemia
vLacticacidemia

--- Content provided by‌ FirstRanker.com ---

vMental retardation
vConvulsions
Pompe's Disease

Enzyme Defect:

--- Content provided by‌ FirstRanker.com ---

Lysosomal (1-4) Glucosidase/Acid Maltase

Biochemical Alterations and Manifestations:

vGlycogen accumulates in Lysosomes of skeletal

--- Content provided by FirstRanker.com ---

and cardiac muscles and affect its function.

vCardiomegaly
vCongestive Heart Failure

--- Content provided by‌ FirstRanker.com ---

vWeakness of respiratory muscles.

Cori's Disease (Limit Dextrinosis)

Enzyme Defect:

--- Content provided by‌ FirstRanker.com ---

Debranching Enzyme Amylo (1-6)

Glucosidase deficiency.

--- Content provided by‍ FirstRanker.com ---

Limit Dextrin gets deposited in Liver

and Muscles.
Macrdle's Disease

--- Content provided by​ FirstRanker.com ---

Enzyme Defect:
Muscle Glycogen Phosphorylase deficiency.

Biochemical alterations and manifestations:

--- Content provided by​ FirstRanker.com ---

No Glycogenolysis in muscles.
Abnormal Glycogen storage in muscles.
Excersise Intolerance.
Muscle cramps
Myoglobinuria.

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Her's Disease

Enzyme Defect:
Hepatic Glycogen Phosphorylase deficiency.

--- Content provided by​ FirstRanker.com ---

Biochemical alterations and manifestations:

No Glycogenolysis in liver.
Abnormal Glycogen storage in hepatocytes.

--- Content provided by‌ FirstRanker.com ---

No correction of fasting Hypoglycemia.
Hepatomegaly
Mild Ketosis.
Frequent feedings of Carbohydrate required.
Tauri's Disease

--- Content provided by‌ FirstRanker.com ---

Enzyme Defect:
Phospho Fructo Kinase deficiency.(Of Glycolysis)

Biochemical alterations and manifestations:

--- Content provided by​ FirstRanker.com ---

Muscle Glycogenolysis is linked with muscle

Glycolysis.

--- Content provided by⁠ FirstRanker.com ---

PFK deficiency of Glycolysis accumulates Glucose-6

-PO4 in muscles.

Glucose-6-PO4 allosterically stimulates

--- Content provided by​ FirstRanker.com ---

Glycogenesis and inhibits Glycogenolysis which

accumulates Glycogen abnormally.

--- Content provided by‍ FirstRanker.com ---

List Of Glycogen Storage Disorders


Type of Glycogen

--- Content provided by FirstRanker.com ---

Name of Glycogen Enzyme Defect

Storage Disorder

Storage Disorder

--- Content provided by​ FirstRanker.com ---

Type I

Von Gierke's Disease Liver Glucose-6-

--- Content provided by⁠ FirstRanker.com ---

Phosphatase

Type II

Pompe's Disease

--- Content provided by​ FirstRanker.com ---

Lysosomal (1-4)

Glucosidase

--- Content provided by⁠ FirstRanker.com ---

Type III

Cori's Disease

Debranching Enzyme

--- Content provided by⁠ FirstRanker.com ---

Type IV

Anderson's Disease

--- Content provided by FirstRanker.com ---

Branching Enzyme

Type V

Macrdle's Disease

--- Content provided by FirstRanker.com ---

Muscle Glycogen

Phosphorylase

--- Content provided by‌ FirstRanker.com ---

Type VI

Her's Disease

Hepatic Glycogen

--- Content provided by​ FirstRanker.com ---

Phosphorylase

Lewi's Disease

--- Content provided by⁠ FirstRanker.com ---

Glycogen Synthase.

Type VII

Tauri's Disease

--- Content provided by FirstRanker.com ---

Phospho Fructo

Kinase.
Pneumonic To Remember

--- Content provided by‍ FirstRanker.com ---

Very Private

Conversation At My

--- Content provided by‌ FirstRanker.com ---

Home Lawn Table.

Hexose Mono Phosphate Shunt
Synonyms

--- Content provided by​ FirstRanker.com ---

HMP Shunt
Pentose Phosphate Pathway (PP

Pathway)

--- Content provided by⁠ FirstRanker.com ---

6-Phosphogluconate Pathway
Direct Oxidative Pathway
Dicken's Horecker Pathway
NADPH+H+ Generating Pathway.

--- Content provided by FirstRanker.com ---

HMP Shunt is an alternative

oxidative pathway of

Glucose.

--- Content provided by FirstRanker.com ---

It's a multifunctional

pathway.

--- Content provided by⁠ FirstRanker.com ---

It has no involvement of ATP.
Do not require Oxygen.
NADPH+H+ is generated.
HMP shunt is more

--- Content provided by⁠ FirstRanker.com ---

anabolic in nature and

generates:

vReducing equivalents-

--- Content provided by‍ FirstRanker.com ---

NADPH+H+

vPentose Sugar-
Ribose-5-Phosphate.

--- Content provided by‍ FirstRanker.com ---

In HMP shunt 6 molecules of

Glucose-6-PO4 makes its entry.

--- Content provided by FirstRanker.com ---

1 molecule of Glucose is oxidized
(6CO2+ 12 NADPH+12H+)
5 molecules of Glucose are

regenerated (Glyceraldehyde-3-

--- Content provided by‍ FirstRanker.com ---

PO4 and Fructose-6-PO4).
NADPH+H+ generated in

HMP shunt supports

--- Content provided by‍ FirstRanker.com ---

Lipogenesis.

Where in well fed condition

--- Content provided by‌ FirstRanker.com ---

free and excess Glucose is

transformed to Fatty acid

and Cholesterol.

--- Content provided by​ FirstRanker.com ---

NADPH+H+ generated

in HMP shunt do not

--- Content provided by​ FirstRanker.com ---

enter in ETC and do

not produce ATPs.
Where HMP Shunt Operates?

--- Content provided by‍ FirstRanker.com ---

Organs and Cel ular Site Of HMP

Shunt

Cytoplasm of Following Tissues:

--- Content provided by‌ FirstRanker.com ---

Liver (30%)
Erythrocytes (30%)
Gonads (10%)
Adrenal Gland (10%)

--- Content provided by‍ FirstRanker.com ---

Adipose Tissue (10%)
Lactating Mammary Gland (10%)
Condition Of Operation Of HMP

HMP shunt operates in

--- Content provided by FirstRanker.com ---

a well fed condition

after a heavy rich

--- Content provided by‌ FirstRanker.com ---

Carbohydrate meals.

Reactions Of HMP Shunt
6(Glucose-6-PO4)+12NADP++6H2O

--- Content provided by‍ FirstRanker.com ---

HMP Shunt

6CO2+12NADPH+12H++

2(Glyceraldehyde-3-PO4)+4(Fructose-6-PO4)

--- Content provided by⁠ FirstRanker.com ---

In HMP Shunt 6(Glucose-6-PO4)=
36 Carbon atoms.
6CO2 and 12 NADPH+H+ generated=
1 Glucose oxidation

--- Content provided by‍ FirstRanker.com ---

30 Carbons are regenerated in the form of

2(Glyceraldehyde-3-PO4)
{ 2x3= 6 Carbons}
4(Fructose-6-PO4)

--- Content provided by‍ FirstRanker.com ---

{4x6=24 Carbons}



HMP shunt includes two

--- Content provided by FirstRanker.com ---

irreversible oxidative

reactions NADP+ dependent.

--- Content provided by‌ FirstRanker.com ---

Series of reversible non

oxidative sugar-phosphate interconversions

(3-7 carbon).

--- Content provided by⁠ FirstRanker.com ---

Transketolase transfers C2 units:

TPP requiring enzyme

Transaldolase transfers C3 units

--- Content provided by FirstRanker.com ---

Two enzymes control the

rearrangement of carbon skeletons

--- Content provided by‌ FirstRanker.com ---

which result in the production of

Glyceraldehyde-3-phosphate and

Fructose-6-phosphate.

--- Content provided by​ FirstRanker.com ---

NADPH Producing Enzymes In

HMP Shunt

--- Content provided by​ FirstRanker.com ---

Glucose-6-P Dehydrogenase
6-P-Gluconate Dehydrogenase
Regulatory Enzyme Of HMP

Glucose-6-PO4 Dehydrogenase

--- Content provided by‍ FirstRanker.com ---

(G6PD) is a regulatory enzyme of

HMP Shunt.

--- Content provided by‌ FirstRanker.com ---

Insulin in well fed condition

stimulates this enzyme and

enhances the operation of HMP

--- Content provided by‍ FirstRanker.com ---

Shunt.

NADPH+ H+ inhibits

--- Content provided by⁠ FirstRanker.com ---

Glucose -6- Phosphate

Dehydrogenase.
Significance Of HMP Shunt

--- Content provided by‌ FirstRanker.com ---

HMP Shunt

predominantly and

uniquely produces

--- Content provided by‍ FirstRanker.com ---

reducing equivalent ?

NADPH+H+
Uses of NADPH+H+

--- Content provided by​ FirstRanker.com ---

NADPH+H+ is used as a coenzyme for

reduction reactions catalyzed by enzyme

--- Content provided by​ FirstRanker.com ---

Reductases during reductive biosynthesis

of :

vFatty acids

--- Content provided by​ FirstRanker.com ---

vCholesterol
vSteroidal Hormones
vCertain Amino acids (GDH activity)

Role Of NADPH+H+ In RBC's

--- Content provided by‌ FirstRanker.com ---

NADPH+H+ in RBC's serve as a

coenzyme for enzyme Glutathione

Reductase.

--- Content provided by‌ FirstRanker.com ---

Glutathione Reductase of RBC's in

turn keeps an enzyme Glutathione

--- Content provided by​ FirstRanker.com ---

Peroxidase( H2O2 detoxifying

enzyme) in reduced and active state.

--- Content provided by​ FirstRanker.com ---

NADPH+ H+ in RBC's

indirectly helps in

detoxification of H2O2

--- Content provided by FirstRanker.com ---

This allows no accumulation

of H2O2 within RBC's.

--- Content provided by⁠ FirstRanker.com ---

In turn maintains cell

membrane integrity and

prevent hemolysis.

--- Content provided by​ FirstRanker.com ---

NADPH+ H+ in RBC's

keeps the Hemoglobin

--- Content provided by FirstRanker.com ---

iron in Ferrous (Fe+2)

state and prevents from

--- Content provided by⁠ FirstRanker.com ---

formation of

Methemoglobinemia

--- Content provided by‌ FirstRanker.com ---

NADPH+ H+ is used in

detoxification of certain

drugs(Mono Oxygenase

--- Content provided by‌ FirstRanker.com ---

System)through

Cytochrome P450 system.

--- Content provided by‌ FirstRanker.com ---

Enzymes Requiring NADPH+H+
De novo Biosynthesis Of Fatty acids

--- Content provided by FirstRanker.com ---

Keto Acyl Reductase
Enoyl Reductase

Cholesterol Biosynthesis:

--- Content provided by⁠ FirstRanker.com ---

HMG CoA Reductase

In R.B.C's

Glutathione Reductase

--- Content provided by‌ FirstRanker.com ---

Methemoglobin Reductase

In Detoxification Process:

Bilirubin Reductase

--- Content provided by FirstRanker.com ---

Cytochrome P450 Reductase

Uronic Acid Pathway

L- Xylulose Reductase

--- Content provided by‌ FirstRanker.com ---

L- Gulonate Reductase
Ribose-5-PO4 another

important byproduct of

--- Content provided by‌ FirstRanker.com ---

HMP Shunt is used for

biosynthesis of

Nucleotides, and certain

--- Content provided by⁠ FirstRanker.com ---

nucleotide coenzymes-

ATP,NAD,FAD and CoA

--- Content provided by FirstRanker.com ---

HMP Shunt is an unique multifunctional

pathway which involves interconversions

of sugars:

--- Content provided by⁠ FirstRanker.com ---

? 3 carbon (Glyceraldehyde-3-PO4)
?4 carbon(Erythrose-4-PO4)
?5 carbon (Ribose-5-PO4)
?6 carbon (Fructose-6-PO4)

--- Content provided by​ FirstRanker.com ---

?7 carbon(Sedoheptulose-7-PO4)
Inborn Error of HMP Shunt

OR

--- Content provided by‍ FirstRanker.com ---

Glucose-6-Phosphate

Dehydrogenase Deficiency

Glucose -6-PO4

--- Content provided by‍ FirstRanker.com ---

Dehydrogenase(G.6.P.D) is the

regulatory or key enzyme of HMP

--- Content provided by FirstRanker.com ---

shunt.

Persons with G.6.P.D deficiency

suffer from Hemolytic Anemia

--- Content provided by​ FirstRanker.com ---

and Hemolytic Jaundice.
G.6.P.D deficiency is sex linked

inherited.

--- Content provided by‍ FirstRanker.com ---

G.6.P.D deficiency blocks HMP shunt

and decreases the levels of

--- Content provided by‌ FirstRanker.com ---

NADPH+H+

Low levels of NADPH+H+ in cells impairs

the cell membrane integrity.

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Lysis of RBC's- Hemolytic Anemia and

Hemolytic Jaundice.

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Consequences Of G.6.P.D

Deficiency In RBC's
G.6.P.D deficiency in RBC's :

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Decreases NADPH+H+ concentration.
Lowers Glutathione Reductase activity.
Lowers the active reduced form of Glutathione

Peroxidase.

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Decreases detoxification of H2O2.
Increases H2O2 levels in cell.(Toxic free radical).
Increases Peroxidation of membrane PUFA's.
Looses cell membrane integrity.

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Lysis of RBC membrane(Hemolysis).
Hemolytic Anemia ,Hemolytic Jaundice,

Methemoglobinemia.

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Individuals with G.6.P.D deficiency

are Resistant to Malaria.

The Reasons for it are:

--- Content provided by FirstRanker.com ---

Low life span of R.B.C's.( Due to

abnormal hemolysis)

Incomplete life cycle of Malarial

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Parasites in such defective

R.B.C's.

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Persons with G.6.P.D

deficiency on ingestion of

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Oxidant Drugs ?Primaquine,

Antipyretics (produces more

H2O2) aggravate the

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condition and leads to

Hemolytic anemia.
Gluconeogenesis

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Synonyms

Neo Glucogenesis.
Biosynthesis of Glucose.

--- Content provided by‌ FirstRanker.com ---

Conversion of Pyruvate to Glucose.
Metabolism Of Lactate.
What Is Gluconeogenesis?

Gluconeogenesis is

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Anabolic process
Carried out in the Cytosol of Liver,
In an emergency condition
Under the influence of hormones

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Glucagon and Epinephrine

Biosynthesis of Glucose from non

Carbohydrate precursors.

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Gluconeogenesis is the process whereby

precursors such as Lactate, Pyruvate,

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Glycerol, and Glucogenic Amino acids are

converted to Glucose.

Fasting requires all the Glucose to be

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synthesized from these non-carbohydrate

precursors.

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Most precursors must enter the Krebs cycle

at some point to be converted to

Oxaloacetate.

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? Humans consume 160 g of Glucose per

day

? 75% of that is used up in the brain

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? Body fluids contain only 20 g of

Glucose

? Glycogen stores yield 180-200 g of

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Glucose

? The body must still be able to make its

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own Glucose

Where Gluconeogenesis Occur?
Organs and Cellular Site For

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Gluconeogenesis:

Organs operating Gluconeogenesis:

Liver (Predominantly)

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Renal Cortex (1/10)

Cellular Site:

Mitochondria and Cytoplasm.

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When Gluconeogenesis Operated?
Gluconeogenesis predominantly takes place

When blood Glucose is low.

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When cellular Glucose is deprived.
In between meals.
In response to Glucagon.

Physiologically In fasting/Starvation conditions.

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Pathologically In Diabetes Mellitus

(In D.M low levels of Insulin and high levels of Glucagon)

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Gluconeogenesis

provides Glucose in slow

and sustained manner in

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response to fall in blood

Glucose.
Glucogenic/Non carbohydrate

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Precursors

The source of Pyruvate and

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Oxaloacetate for

Gluconeogenesis during fasting

or carbohydrate starvation is

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Mainly from Amino acid

catabolism.
Pyruvate (Predominant precursor)

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Lactate(Anaerobic and Erythrocyte

Glycolysis)

Propionyl-CoA

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(oxidation of odd chain fatty acid and

Amino acid catabolism)

Glycerol (Lipolysis, TAG breakdown)

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Glucogenic Amino acids
(Ala, Asp, Ser, Gly, Tyr, Trp, His)
Intermediates of TCA cycle

How Gluconeogenesis Occur?

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Steps Of Gluconeogenesis

Glycolysis converts

Glucose to Pyruvate.

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Gluconeogenesis

converts Pyruvate to

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Glucose.
Gluconeogenesis and

Glycolysis are not exactly

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same but differs in their

irreversible steps.

The reversible enzymes of

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both the pathways are same.

? In Gluconeogenesis

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? Seven steps of Glycolysis are

retained.

? Three steps are replaced.

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Three irreversible enzymes of Glycolysis.

w Glucokinase
w Phosphofructokinase
w Pyruvate Kinase

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These 3 steps are bypassed in Gluconeogenesis.

w Glucose-6-Phosphatase
w Fructose-1,6-Bis Phosphatase

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w PEP Carboxy Kinase (GTP dependent)
w Pyruvate Carboxylase( Requires ATP and Biotin)

Oxaloacetate is the starting

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material for Gluconeogenesis
Conversion of Pyruvate to

PEP

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Is in two irreversible steps
With two enzymes
Requiring ATP and GTP

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Pyruvate is converted to Oxaloacetate before

being changed to PhosphoenolPyruvate

1. Pyruvate Carboxylase catalyses the ATP-driven

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formation of Oxaloacetate from Pyruvate and

CO2
2. PEP Carboxykinase (PEPCK) converts

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Oxaloacetate to PEP that uses GTP as a

phosphorylating agent.

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Pyruvate Carboxylase

? The reaction requires ATP and bicarbonate as

substrates

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? Biotin cofactor
? Acetyl-CoA is an allosteric activator
? Regulation: when ATP or acetyl-CoA are high,

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Pyruvate enters gluconeogenesis
PEP Carboxykinase

Not an allosteric enzyme
Rxn reversible in vitro but irreversible

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in vivo

Activity is mainly regulated by control

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of enzyme levels by modulation of

gene expression

Glucagon induces increased PEP

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Carboxykinase gene expression

Fructose-1,6-Bisphosphatase

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? Allosteric regulation:

? Citrate stimulates
? Fructose-2,6--Bisphosphate inhibits
? AMP inhibits

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Glucose-6-Phosphatase

? Presence of G-6-Pase in ER of liver and kidney

--- Content provided by​ FirstRanker.com ---

cells makes gluconeogenesis possible

? Muscle and brain do not do gluconeogenesis
? G-6-P is hydrolyzed as it passes into the ER

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? ER vesicles filled with glucose diffuse to the

plasma membrane, fuse with it and open,

releasing glucose into the bloodstream.

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ATP Use In Gluconeogenesis

2 ATPs are used in Pyruvate Carboxylase

reaction of Gluconeogenesis.

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2 GTPs are used in PEP Carboxykinase

step of Gluconeogenesis generated in

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TCA cycle.

2 ATPs are used in Phospho Glycerate

Kinase activity.

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Net 6 ATP's are utilized

during Gluconeogenesis

for biosynthesis of

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1 Glucose molecule from
2 molecules of Pyruvate.

Entry Of Glucogenic Precursors

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For Gluconeogenesis


Regulation Of Gluconeogenesis

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Regulatory Enzymes Of

Gluconeogenesis

Four irreversible enzymes of

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Gluconeogenesis are its regulatory

enzymes.

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vPyruvate Carboxylase
vPEP Carboxy Kinase.
vFructose-1,6-Bis Phosphatase.
vGlucose-6- Phosphatase.

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Gluconeogenesis and

Glycolysis are reciprocally

regulated ,i.e if one

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pathway is active another

is relatively inactive.
In a well fed condition

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Insulin inhibits

Gluconeogenesis.

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In emergency condition

Glucagon stimulates

Gluconeogenesis.

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To prevent the waste of a

futile cycle, Glycolysis &

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Gluconeogenesis are

reciprocally regulated.
Glucagon via cAMP cascade of

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reactions brings covalent

modification of enzymes.

Pyruvate Carboxylase.

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PEP Carboxy Kinase.

Stimulate Gluconeogenesis.
Simultaneously Glucagon Inhibits

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Pyruvate Kinase of Glycolysis.

Substrate Availability and

Regulation Of Gluconeogenesis

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Increased availability of

Glucogenic precursors viz

Lactate ,Glycerol, products of

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Glucogenic amino acids

influences the rate of

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Gluconeogenesis.

Excess Acetyl-CoA in emergency

condition Al osterical y Stimulates

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Gluconeogenesis
In fasting or emergency condition .
Glucose metabolism decreased.
Lipid metabolism increased.

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Increased Lipolysis.
Increased Oxidation of Fatty acids.
Increased Acetyl-CoA.
Acetyl-CoA stimulates Pyruvate

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Carboxylase for OAA synthesis.

Simulates Gluconeogenesis.

Acetyl-CoA regulates Pyruvate

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Carboxylase

Increases in Oxaloacetate concentrations

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increase the activity of the Krebs cycle

and Acetyl-CoA is an allosteric activator

of the Carboxylase.

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However when ATP and NADH

concentrations are high and the Krebs

cycle is inhibited, Oxaloacetate goes

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to Glucose.
Pyruvate Carboxylase

(Pyruvate Oxaloactate) is allosterically activated by

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acetyl CoA.

[Oxaloacetate] tends to be limiting for Krebs cycle.

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When Gluconeogenesis is active in Liver, Oxaloacetate

is diverted to form Glucose.

Oxaloacetate depletion hinders acetyl CoA entry into

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Krebs Cycle.

The increase in [acetyl CoA] activates Pyruvate

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Carboxylase to make Oxaloacetate.

Reciprocal Regulation By

Fructose-2,6-bisphosphate

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The allosteric regulator

Fructose-2,6-

bisphosphate is

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synthesized & degraded by

a bi-functional enzyme

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that includes 2 catalytic

domains:

Fructose-2,6-

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bisphosphate is

synthesized from excess

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Glucose in well fed

condition.

w Fructose-2,6-bisphosphate

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stimulates Glycolysis.
Fructose-2,6-bisphosphate

allosterically activates the

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Glycolysis enzyme

PhosphoFructokinase 1(PFK1).

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Fructose-2,6-

bisphosphate allosterically

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inhibits the

Gluconeogenesis enzyme

Fructose-1,6-

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bisphosphatase.

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Significance Of Gluconeogenesis
Glucose is a primary source of energy.
Brain and Erythrocytes are totally

dependent upon Glucose for its energy in

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all states.

Blood Glucose in fasting condition

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should be maintained to 70-110 mg%.

Gluconeogenesis operates in critical

emergency conditions when blood

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Glucose go below subnormal.

Gluconeogenesis

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endogenously produces

Glucose in Liver using

non carbohydrate

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precursors and regulate

blood Glucose levels.
Thus Gluconeogenesis corrects fasting

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Hypoglycemia and try to maintain the

fasting blood Glucose of 70-110 mg%.

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Gluconeogenesis helps in supply of Glucose

to Brain and Erythrocytes in emergency

condition and maintain their functions.

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Gluconeogenesis by its operation

metabolizes Lactate, Propionyl CoA, and

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Glycerol obtained from other metabolic

pathways.

Cori's Cycle

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and

Glucose Alanine Cycle
Cori's cycle

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metabolizes Muscle

Lactate produced in

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anaerobic condition.

The Cori Cycle operates during

exercise.

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Lactate produced from Pyruvate in

muscles in anaerobic condition ,passes

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via the blood to the Liver, where it may

be converted to Glucose by

Gluconeogenesis.

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The Glucose may travel back to the

muscle to fuel Glycolysis.

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Glucose Alanine Cycle

(Cahil Cycle)

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Glucose Alanine Cycle is

important during starvation.

Glucose Alanine cycle is

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intimately related with Cori's

cycle.

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The Cori cycle costs 6 ~P in liver for every 2 ~P made

available in muscle. The net cost is 4 ~P.

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Although costly in ~P bonds, the Cori Cycle allows

the organism to accommodate to large fluctuations

in energy needs of skeletal muscle between rest and

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exercise.
Energy dissipation by the Cori Cycle, which expends

6 ~P in liver for every 2 ~P produced via Glycolysis for

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utilization within the tumor, is thought to contribute to

the weight loss that typically occurs in late-stage

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cancer even when food intake remains normal.

GN Ratio or DN Ratio

Glucose Nitrogen

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Ratio

Dextrose Nitrogen

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Ratio
During Starvation Muscle

Proteins are degraded to release

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Glucogenic precursors(G).

Nitrogenous Urea end product

of Protein catabolism excreted

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out through urine(N).

GN ratio =3.65
1 gm of Urea nitrogen

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produced will form 3.65 gm

of Glucose.

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Protein contains 16%

Nitrogen.

58% of Protein is Glucogenic

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G N ratio gives idea of

amount of body Protein

degradation which

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provide precursors for

Glucose production in

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emergency conditions.

GN ratio is enhanced in

Insulin deficiency

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Increased body Protein degradation
Starvation
Pyrexia
Hyperthyroidism
Cancer

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Uronic Acid Pathway
Significance Of Uronic Acid

Pathway

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Uronic Acid Pathway is minor

Oxidative Pathway of Glucose.

Uronic Acid Pathway oxidizes Glucose

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to Glucuronic acid.

UDP-Glucuronate is an activated

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molecule produced in Uronic Acid

Pathway which has specific roles in the

body.

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Functions of UDP-Glucuronate:

UDP-Glucuronate is a repeating

unit of Mucopolysaccharides/

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Glycosaminoglycans of human

body.

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UDP-Glucuronate is

component of Glycolipids-

Cerebrosides and Gangliosides.

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UDP-Glucuronate

serve as a conjugating

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agent for

detoxification reactions

in Liver.

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Bilirubin in Liver is

conjugated with 2 molecules

of UDP-Glucuronate to form

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Bilirubin di Glucuronide

[conjugated Bilirubin ]

--- Content provided by‍ FirstRanker.com ---

Inborn Error Of Uronic Acid

Pathway
Essential Pentosuria is an inborn error

--- Content provided by‌ FirstRanker.com ---

of Uronic Acid Pathway.

Essential Pentosuria is also a member of

Garrod's Tetrad.

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Enzyme Defect:

Xylitol Dehydrogenase/L-Xylulose

--- Content provided by​ FirstRanker.com ---

Reductase.

Abnormally L-Xylulose(Pentose)

accumulated in blood and excreted out

--- Content provided by‍ FirstRanker.com ---

in urine.

Galactose Metabolism
Sources of Galactose

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Dietary Exogenous Source of

Galactose:

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Lactose- Milk and Milk Products.
Digestion of Lactose by Lactase

liberates Galactose and Glucose.

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Bodies Endogenous Source of

Galactose:

Breakdown product of GAG's,

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Glycoprotein and Glycolipids.
Infants major food is

milk.

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Galactose is equally

present along with

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Glucose in their GIT.

Absorption And Fate Of Galactose
Galactose from an intestinal

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lumen is actively absorbed

with relative coefficient of

absorption of 110.

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Galactose absorbed in intestinal

mucosal cells diffuse into

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Hepato Portal circulation and

carried to Liver.

Galactose in Liver is

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metabolized and

transformed to Glucose.

--- Content provided by‍ FirstRanker.com ---

Inborn Errors Of Galactose

Metabolism

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Galactosaemia

Enzyme Deficient: Galactokinase

Biochemical Alterations:

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Galactose not metabolized to Glucose.
No phosphorylation of Liver Galactose to

Galactose-1-PO4.

--- Content provided by​ FirstRanker.com ---

Free Galactose(permeable) from Liver, move

out in blood.

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Galactosemia-Increased levels of Galactose

in blood.

Galactosuria-Galactose excreted in urine.

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Galactosemia Leads To Cataract

In Galactosemia the high levels of

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blood Galactose rich to eyes and get

accumulated.

In the lens cells the accumulated

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Galactose is reduced to Galactitol.

Galactitol in lens cause opaqueness

--- Content provided by‌ FirstRanker.com ---

of lens.

Causing Cataract.
Classical Galactosemia

--- Content provided by​ FirstRanker.com ---

Enzyme Deficient:

Galactose-1-PO4 Uridyl Transferase.

Biochemical Alterations and Clinical

--- Content provided by‌ FirstRanker.com ---

Manifestations:

Blocks the conversion of Gal-1-po4 to UDP-Galactose.
Accumulation of Galactose-1-po4 in Hepatocytes.

--- Content provided by​ FirstRanker.com ---

Hepatomegaly
Splenomegaly
Loss of Weight
Weakness
Hepatic Jaundice.

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Mental Retardation
Infants (Milk fed) whose

principle dietary

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carbohydrate is Galactose

are more affected during

inborn error of Galactose

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metabolism.

Fructose Metabolism
Sources Of Fructose

--- Content provided by‌ FirstRanker.com ---

Fructose is present in free form in

Fruits and Honey.

--- Content provided by‌ FirstRanker.com ---

Fructose is a component of Sucrose.
Sucrose digestion by Sucrase liberates

free Glucose and Fructose.

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Endogenously Fructose is richly

present in seminal fluid.

Absorption and Fate Of Fructose

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Fructose from intestinal lumen is

absorbed by facilitated diffusion.

--- Content provided by FirstRanker.com ---

From intestinal mucosal cells it is

carried to Liver by Hepato Portal

circulation.

--- Content provided by⁠ FirstRanker.com ---

In liver Fructose is

metabolized to Glucose

--- Content provided by‌ FirstRanker.com ---

and utilized.
Inborn Errors Of Fructose

Metabolism

--- Content provided by⁠ FirstRanker.com ---

Essential Fructosuria

Enzyme Defect: Liver Fructokinase
Biochemical Alterations and Manifestations:

--- Content provided by​ FirstRanker.com ---

Blocks the phosphorylation of Fructose to Fructose-1-PO4.
Free Fructose is permeable ,come out of Liver.
High levels of Fructose in blood and urine.
Fructosuria.

--- Content provided by FirstRanker.com ---

Asymptomatic.
Restrict Sucrose and Fructose in diet.
Hereditary Fructose

Intolerance/Fructose Poisoning

--- Content provided by⁠ FirstRanker.com ---

Enzyme Defect:
Aldolase- B
Inheritance:
Autosomal recessive

--- Content provided by⁠ FirstRanker.com ---

Incidence:
1 in 20,000 births

Biochemical Alterations and Clinical

--- Content provided by‍ FirstRanker.com ---

Manifestations:

Fructose-1-PO4 not further

metabolized and accumulates in

--- Content provided by‌ FirstRanker.com ---

hepatocytes.

Affects normal functioning of Liver.
Depletion of inorganic

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Phosphorous(pi).

Decreases Glycolysis ,Glycogenesis and

--- Content provided by​ FirstRanker.com ---

Gluconeogenesis.
Classical manifestations of hereditary

Fructose intolerance:

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Hypoglycemia
Hepatomegaly.
Hepatic Jaundice.
Diagnosis:
Benedict's and Selivanoff's Test.

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Management:
Diet free of Sucrose and Fructose.

Homeostasis Of Blood Glucose

--- Content provided by​ FirstRanker.com ---

OR

Factors Regulating Blood Glucose
What is Homeostasis?

--- Content provided by⁠ FirstRanker.com ---

Homeostasis is a

physicochemical process in the

body, where the altered levels

--- Content provided by‌ FirstRanker.com ---

are tried to maintained to

normal levels.

--- Content provided by FirstRanker.com ---

Biochemical homeostasis means

keeping the biochemical

constituents within normal range.

--- Content provided by⁠ FirstRanker.com ---

Homeostasis of blood Glucose

means keeping the blood Glucose

--- Content provided by‍ FirstRanker.com ---

within normal range.
Normal homeostatic

mechanism maintains

--- Content provided by‌ FirstRanker.com ---

bodies health.

Defect in homeostatic

mechanisms leads to:

--- Content provided by‍ FirstRanker.com ---

No corrections of altered levels

of biochemical constituents.

--- Content provided by‍ FirstRanker.com ---

Biochemical constituents vary

from normal range leading to

hyper and hypo values.

--- Content provided by⁠ FirstRanker.com ---

Leads to Metabolic disorders.


Normal Ranges Of Blood Glucose:

--- Content provided by⁠ FirstRanker.com ---

Fasting Blood Glucose(F)= 70-110 mg%
(After 10-12 hours of fast)
Post Prandial(PP) Blood Glucose= 120-160mg%
(1 ? -2 hours after meals)

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Random Blood Glucose= 80-140 mg%.
(Any Time of the day)
Homeostatic Factors Regulating

Blood Glucose:

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Hormones

Blood Glucose Regulating Hormones:

--- Content provided by FirstRanker.com ---

Hypoglycemic/ Blood Glucose Lowering

Hormone/ Anti Diabetogenic :

INSULIN

--- Content provided by FirstRanker.com ---

Hyperglycemic/ Blood Glucose

Increasing Hormones Diabetogenic :

Glucagon

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Epinephrine (Adrenaline)
Thyroid Hormone
Growth Hormone
Glucocorticoids.

--- Content provided by‍ FirstRanker.com ---

Organs And Metabolic Pathways

Operating In It:

Liver ( Glucostatic Organ )

--- Content provided by‍ FirstRanker.com ---

Muscles
Adipose Tissue
Kidney.
Healthy normal

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functioning of organs and

the related metabolic

pathways is essential for

--- Content provided by⁠ FirstRanker.com ---

normal blood Glucose

regulation.

--- Content provided by FirstRanker.com ---

INSULIN


Incretin - Gut Hormones

--- Content provided by FirstRanker.com ---

Stimulates Insulin Secretion.

Gut hormones GIP (Glucose dependent

Insulinotropic Peptide) and GLP-1

--- Content provided by FirstRanker.com ---

(Glucagon Like Peptide-1) produced in

response to Glucose in intestine.

--- Content provided by‍ FirstRanker.com ---

Incretin reach and activate the Pancreas

for robust Insulin secretion, in

anticipation of the rise in blood Glucose ,

--- Content provided by​ FirstRanker.com ---

after meals.
Hormone Insulin get secreted by

cells of Islets of Langerhans of

--- Content provided by​ FirstRanker.com ---

Pancreas in response to increased

blood Glucose levels in a well fed

--- Content provided by FirstRanker.com ---

condition:

Insulin helps in transportation

of Glucose in peripheral tissues.

--- Content provided by‍ FirstRanker.com ---

Stimulates all the key or

regulatory enzymes of

--- Content provided by‍ FirstRanker.com ---

metabolic pathways which

metabolizes the entered Glucose

in cells.

--- Content provided by​ FirstRanker.com ---

Insulin by its activity stimulates and

increases Glucose utilizing pathways in

well fed condition:

--- Content provided by FirstRanker.com ---

vGlycolysis.
vGlycogenesis
vLipogenesis
vHMP Shunt

--- Content provided by​ FirstRanker.com ---

vUronic Acid Pathway

Insulin by its activity

simultaneously inhibits and

--- Content provided by FirstRanker.com ---

decreases Glucose producing

pathways:

--- Content provided by‍ FirstRanker.com ---

?Glycogenolysis
?Gluconeogenesis


Counter Regulatory Hormones

--- Content provided by FirstRanker.com ---

Glucagon ( From cells of islets of

Langerhans)

--- Content provided by⁠ FirstRanker.com ---

Epinephrine (Hypothalamic Glucoreceptors,

mediated by ANS)

Growth Hormone ( Anterior Pituitary)

--- Content provided by FirstRanker.com ---

Cortisol (Adrenal Cortex- mediated by ACTH)
All these hormones opposes the action of

insulin on Glucose use.
Glucagon and Epinephrine are most

--- Content provided by‌ FirstRanker.com ---

important in the acute and short

term regulation of blood Glucose

--- Content provided by FirstRanker.com ---

levels.

Glucagon stimulates Liver

Glycogenolysis and Gluconeogenesis.

--- Content provided by‌ FirstRanker.com ---

Epinephrine stimulates

Glycogenolysis and Lipolysis.

--- Content provided by⁠ FirstRanker.com ---

Epinephrine inhibits insulin

secretion.

Epinephrine inhibits insulin

--- Content provided by FirstRanker.com ---

mediated uptake of Glucose by

peripheral tissues.

--- Content provided by⁠ FirstRanker.com ---

Epinephrine is not so essential if

Glucagon is functioning.
Cortisol and Growth

--- Content provided by FirstRanker.com ---

Hormone are important

in the long term

management of Glucose

--- Content provided by⁠ FirstRanker.com ---

metabolism.

Insulin

--- Content provided by​ FirstRanker.com ---

Glucagon

Insulin is a polypeptide

Glucagon is a polypeptide

--- Content provided by⁠ FirstRanker.com ---

hormone composed of 51

hormone composed of 29

--- Content provided by‌ FirstRanker.com ---

amino acids

amino acids.

Structure has two

--- Content provided by⁠ FirstRanker.com ---

Structure has one

polypeptide chains 21 and 30 polypeptide chain

--- Content provided by⁠ FirstRanker.com ---

amino acids.
Insulin is synthesized and

Glucagon is secreted by alpha

--- Content provided by‌ FirstRanker.com ---

secreted by beta cells of Islets cells of Islets of Langerhans

of Langerhans of Pancreas.

of Pancreas.

--- Content provided by FirstRanker.com ---

Insulin is secreted in

Glucagon is secreted in

--- Content provided by‌ FirstRanker.com ---

response to high blood

response to low blood

Glucose and Aminoacid

--- Content provided by​ FirstRanker.com ---

Glucose

levels.
Insulin

--- Content provided by‍ FirstRanker.com ---

Glucagon

Epinephrine inhibits

--- Content provided by⁠ FirstRanker.com ---

Epinephrine stimulates

Insulin secretion

Glucagon secretion.

--- Content provided by​ FirstRanker.com ---

Insulin by its activity

Glucagon by its activity

--- Content provided by‍ FirstRanker.com ---

lowers the blood

raises the blood Glucose.

Glucose. Insulin

--- Content provided by‍ FirstRanker.com ---

Glucagon is Glucose

Glucose utilizing

--- Content provided by‍ FirstRanker.com ---

producing hormone

hormone
Insulin stimulates all

--- Content provided by FirstRanker.com ---

Glucagon stimulates

pathways of Glucose

Glycogenolysis and

--- Content provided by‌ FirstRanker.com ---

operating in a well fed Gluconeogenesis in

condition which

--- Content provided by⁠ FirstRanker.com ---

emergency fasting

metabolizes cellular

condition.

--- Content provided by FirstRanker.com ---

Glucose.Insulin

Glucagon

--- Content provided by⁠ FirstRanker.com ---

Insulin deficiency leads Glucagon deficiency

to persistent

leads to persistent

--- Content provided by‌ FirstRanker.com ---

Hyperglycemia

hypoglycemia

--- Content provided by FirstRanker.com ---

Insulin for its action Glucagon for its

do not use cyclic AMP.activity uses cyclic

AMP.

--- Content provided by‌ FirstRanker.com ---

Insulin stimulates

Glucagon stimulates

--- Content provided by⁠ FirstRanker.com ---

Glycogenesis,

Glycogenolysis,

Lipogenesis, Protein Lipolysis, Protein

--- Content provided by​ FirstRanker.com ---

biosynthesis.

degradation.
Homeostatic Mechanism Of Blood

--- Content provided by FirstRanker.com ---

Glucose:

In a well fed condition after heavy meals

--- Content provided by​ FirstRanker.com ---

Glucose added to blood

Increased blood Glucose(Transient Hyperglycemia)

Insulin secreted

--- Content provided by FirstRanker.com ---

Mediates Glucose uptake by peripheral tissues

(GluT4 Insulin dependent)

--- Content provided by⁠ FirstRanker.com ---

Regulates the increased blood Glucose
In a fasting condition /Between meals

Blood Glucose is utilized

--- Content provided by⁠ FirstRanker.com ---

Decreased blood Glucose(Transient Hypoglycemia)

Glucagon and Epinephrine secreted

Stimulates Glucose producing pathways of Liver

--- Content provided by⁠ FirstRanker.com ---

Glycogenolysis and Gluconeogenesis Increased

Glucose added to blood

--- Content provided by FirstRanker.com ---

Regulates the decreased blood Glucose

Significance Of Blood Glucose

Regulation

--- Content provided by‌ FirstRanker.com ---

A constant source of blood Glucose

is an absolute requirement for

human life.

--- Content provided by⁠ FirstRanker.com ---

Glucose is the greatly preferred

energy source for Brain,

--- Content provided by​ FirstRanker.com ---

Erythrocytes.

Glucose is essential for exercising

muscles.

--- Content provided by FirstRanker.com ---

Homeostatic mechanism of blood Glucose :
Corrects transient hyperglycemia after a well fed

state.

--- Content provided by‌ FirstRanker.com ---

Corrects transient hypoglycemia in a fasting

condition.

--- Content provided by‌ FirstRanker.com ---

Maintain a constant normal range of blood

Glucose in specific conditions of body.

Helps in continuous supply of Glucose to tissues

--- Content provided by FirstRanker.com ---

which are totally dependent on Glucose.

Try to keep the Brain and Erythrocytes vital and

--- Content provided by FirstRanker.com ---

active
Disorders Of Blood Glucose

Regulation

--- Content provided by⁠ FirstRanker.com ---

Causes of abnormal blood

Glucose regulation:

Defects in Hormonal secretion

--- Content provided by‍ FirstRanker.com ---

and their activities.

Diseased organ system.
Deranged metabolic pathways

--- Content provided by‍ FirstRanker.com ---

associated to Glucose.
Defect in factors regulating

blood Glucose:

--- Content provided by⁠ FirstRanker.com ---

Does not correct transient

Hyperglycemia and

--- Content provided by‍ FirstRanker.com ---

Hypoglycemia.

Leads to persistent

Hyperglycemia and

--- Content provided by FirstRanker.com ---

Hypoglycemia.

Persistent Hyperglycemia

--- Content provided by FirstRanker.com ---

Persistent hyperglycemia is characterized with

chronic abnormal high levels of blood Glucose.

Persistent Hyperglycemia is noted in:

--- Content provided by‌ FirstRanker.com ---

Diabetes mellitus.
Stress, Anxiety
Hyperadrenalism
Hyperthyroidism

--- Content provided by‌ FirstRanker.com ---

Hyperpituitarism
Persistent Hypoglycemia

Persistent hypoglycemia is characterized with

--- Content provided by‌ FirstRanker.com ---

abnormal low levels of blood Glucose.

Persistent Hypoglycemia is noted in:

Prolonged Starvation

--- Content provided by‍ FirstRanker.com ---

Tumors of pancreas
High dose of insulin during insulin therapy
Alcoholism

Types Of Hypoglycemia

--- Content provided by‍ FirstRanker.com ---

Insulin ?Induced

Hypoglycemia

--- Content provided by FirstRanker.com ---

Post Prandial Hypoglycemia
Fasting Hypoglycemia
Alcoholic Intoxication-

Hypoglycemia

--- Content provided by‍ FirstRanker.com ---

Insulin induced hypoglycemia-

High dosage of Insulin while

treating Type I Diabetes mellitus.

--- Content provided by‍ FirstRanker.com ---

Glucagon is administered

subcutaneously or intramuscularly

--- Content provided by FirstRanker.com ---

to unconscious patients who have

lost the ability to coordinate

swallowing.

--- Content provided by⁠ FirstRanker.com ---

Post prandial Hypoglycemia-

Caused by exaggerated insulin

--- Content provided by‌ FirstRanker.com ---

release after meals.

Transient hypoglycemia with mild

adrenergic symptoms.

--- Content provided by⁠ FirstRanker.com ---

Manage the condition by advising

the patients to take frequent small

--- Content provided by FirstRanker.com ---

meals rather than usual three large

meals.
Fasting Hypoglycemia-

--- Content provided by​ FirstRanker.com ---

In fasting condition.
In pancreatic tumors- large insulin

secretions.

--- Content provided by‌ FirstRanker.com ---

Hepatic damage- low Glycogenolysis and

Gluconeogenesis

Adrenal insufficiency

--- Content provided by‌ FirstRanker.com ---

Show Neuroglycopenic symptoms
Convulsions and Coma

Alcoholic Intoxication-

--- Content provided by‍ FirstRanker.com ---

Hypoglycemia
Persons in fasting

condition(depleted stores of

--- Content provided by​ FirstRanker.com ---

Glycogen) intoxicated with alcohol.

Alcohol metabolism produces

abundance of NADH+H+

--- Content provided by FirstRanker.com ---

Alcohol metabolism inhibits

Gluconeogenesis.

--- Content provided by‌ FirstRanker.com ---

Decreases the Glucose synthesis.

Consequences of Hypoglycemia

Transient hypoglycemia can

--- Content provided by‍ FirstRanker.com ---

cause cerebral dysfunction.

Persistent ,prolonged

--- Content provided by FirstRanker.com ---

hypoglycemia causes brain

death.
Symptoms Of Hypoglycemia

--- Content provided by FirstRanker.com ---

Adrenergic Symptoms:
( Due to elevated epinephrine , when abrupt fall in

blood Glucose at 65 mg% )

--- Content provided by‍ FirstRanker.com ---

Anxiety
Palpitation
Headache
Confusion
Tremors

--- Content provided by​ FirstRanker.com ---

Sweating
Neuroglycopenic Symptoms:
(Due to impaired delivery of Glucose to brain,

when blood glucose drops gradually at 50 mg%)

--- Content provided by‌ FirstRanker.com ---

Slurred Speech
Seizures
Coma
Death

--- Content provided by‌ FirstRanker.com ---

Hypoglycemia is more

serious than hyperglycemia.

--- Content provided by FirstRanker.com ---

Brain does not get sufficient

Glucose in hypoglycemic

conditions.

--- Content provided by​ FirstRanker.com ---

One should manage

hypoglycemia more rapidly

--- Content provided by‍ FirstRanker.com ---

to avoid brain dysfunction.
Correction Of Hypoglycemia

Hypoglycemia is a medical emergency

--- Content provided by FirstRanker.com ---

which should be immediately attended

and resolved to have proper brain

function.

--- Content provided by‌ FirstRanker.com ---

Administration of Glucose

intravenously resolves the symptoms

--- Content provided by⁠ FirstRanker.com ---

of hypoglycemia within minutes.

Hyperglycemia

Hypoglycemia

--- Content provided by FirstRanker.com ---

Blood glucose increased Blood Glucose decreased

above normal range.

--- Content provided by⁠ FirstRanker.com ---

below normal range.

Caused due to

Caused due to excess

--- Content provided by​ FirstRanker.com ---

insufficiency or

activity of Insulin.

--- Content provided by​ FirstRanker.com ---

inefficiency of Insulin.
Predominant in Diabetes Noted in Insulinomas

mellitus.
Hyperglycemia is less

--- Content provided by FirstRanker.com ---

Hypoglycemia is more

severe and do not affect serious , affects normal

--- Content provided by‌ FirstRanker.com ---

brain function.

function of brain.

Hyperglycemia may lead Hypoglycemia condition

--- Content provided by‍ FirstRanker.com ---

to Glycosuria.

shows no Glycosuria.

--- Content provided by⁠ FirstRanker.com ---

Diabetes Mellitus (DM)
What is Diabetes mellitus?

Diabetes mellitus is

--- Content provided by⁠ FirstRanker.com ---

Most common (3rd leading cause of death)
Heterogeneous, wide spread
Endocrine, metabolic disorder
Characterized by chronic persistent

--- Content provided by‍ FirstRanker.com ---

hyperglycemia.

Causes/Etiological Factors:

--- Content provided by‌ FirstRanker.com ---

Basic cause for Diabetes mellitus is :

Insulin insufficiency
Insulin inefficiency
Diabetes Mellitus is a

--- Content provided by⁠ FirstRanker.com ---

disorder due to defect

in blood Glucose

--- Content provided by⁠ FirstRanker.com ---

regulation.

Hormone Insulin

which regulates blood

--- Content provided by‌ FirstRanker.com ---

glucose levels is

affected in Diabetes

--- Content provided by FirstRanker.com ---

mellitus.
Low/No insulin activity in

DM does not transport

--- Content provided by‌ FirstRanker.com ---

Glucose within peripheral

cells leading to persistent

hyperglycemia.

--- Content provided by FirstRanker.com ---

Multiple and Complex Etiological

Factors Of Diabetes Mellitus:
Hereditary

--- Content provided by⁠ FirstRanker.com ---

Race
Nutritional Status
Stress
Drug Interaction
Endocrine Dysfunction

--- Content provided by​ FirstRanker.com ---

Infections
Autoimmunity
Occupational
Living Style
Various other Environmental Factors

--- Content provided by‍ FirstRanker.com ---

Modern Life style ,food

habits, stress ,and

--- Content provided by‌ FirstRanker.com ---

polluted environment

are likely to increase the

number of sufferers of

--- Content provided by‍ FirstRanker.com ---

Diabetes Mellitus.
Geographical Distribution/

Prevalence Of DM

--- Content provided by‍ FirstRanker.com ---

Diabetes mellitus is a substantial

global health problem.

--- Content provided by‍ FirstRanker.com ---

Widely spreaded in every part of

world.

More than 20 million people are

--- Content provided by​ FirstRanker.com ---

sufferers of DM world wide.

Classification/Types Of DM

--- Content provided by‍ FirstRanker.com ---

WHO Classification of Diabetes mellitus:

Type 1/IDDM/Juvenile Onset DM

Type 2/NIDDM/Maturity Onset DM

--- Content provided by FirstRanker.com ---

Gestational Diabetes mellitus(GDM)
Type 1 Diabetes Mellitus

Type 1 DM

--- Content provided by FirstRanker.com ---

Juvenile Onset
Initiated by environmental factor/ viral infection.
Abrupt onset
Cellular mediated autoimmune destruction of the

--- Content provided by⁠ FirstRanker.com ---

beta cells of the pancreas

Absolute deficiency of insulin secretion.
Insulin dependence

--- Content provided by‍ FirstRanker.com ---

Ketosis tendency
Presence of islet cell autoantibodies, insulin auto

antibodies in blood circulation.

--- Content provided by⁠ FirstRanker.com ---

Type 2 Diabetes Mellitus

Type 2 DM

--- Content provided by‌ FirstRanker.com ---

Maturity Onset Diabetes
Has resistance to Insulin
Insulin secretory defect
Not absolute insulin deficiency
Strong genetic predisposition

--- Content provided by⁠ FirstRanker.com ---

Prone to obese and sedentary life

persons

Milder type

--- Content provided by⁠ FirstRanker.com ---

Character

IDDM

NIDDM

--- Content provided by⁠ FirstRanker.com ---

Prevalence

10-20%

--- Content provided by⁠ FirstRanker.com ---

80-90%

Age Of Onset

< 20 Years

--- Content provided by‍ FirstRanker.com ---

> 30 Years

Body Weight

--- Content provided by​ FirstRanker.com ---

Normal/Low

Obese/Over

weight

--- Content provided by⁠ FirstRanker.com ---

Genetic

Moderate

--- Content provided by​ FirstRanker.com ---

Very Strong

Predisposition
Defect

--- Content provided by⁠ FirstRanker.com ---

Insulin

Insulin

deficiency-

--- Content provided by‌ FirstRanker.com ---

inefficiency-

Destruction of Insulin

--- Content provided by⁠ FirstRanker.com ---

cells of Pancreas Resistance ,

defect in Insulin

receptors.

--- Content provided by‍ FirstRanker.com ---

Character

IDDM

--- Content provided by‍ FirstRanker.com ---

NIDDM

Plasma Insulin Low or absent

Normal /

--- Content provided by⁠ FirstRanker.com ---

Increased

Auto Antibodies Frequently

--- Content provided by‌ FirstRanker.com ---

Rare

found

Severity

--- Content provided by‌ FirstRanker.com ---

More severe

Mild

--- Content provided by‌ FirstRanker.com ---

Treatment

Insulin Doses

Hypoglycemic

--- Content provided by⁠ FirstRanker.com ---

Drugs.

Acute

--- Content provided by‌ FirstRanker.com ---

Diabetic

Hyperosmolar

Complications Ketoacidosis

--- Content provided by‍ FirstRanker.com ---

Coma

Ketosis

--- Content provided by​ FirstRanker.com ---

Ketosis

common.

Rare.

--- Content provided by FirstRanker.com ---

Gestational Diabetes Mellitus

(GDM)

--- Content provided by​ FirstRanker.com ---

Glucose intolerance during pregnancy.
Affects approximately 4 % of pregnant

women.

--- Content provided by‌ FirstRanker.com ---

Caused due to metabolic and

hormonal changes during pregnancy

--- Content provided by‍ FirstRanker.com ---

Women with GDM frequently return

to normal postpartum.
Gestational diabetes

--- Content provided by FirstRanker.com ---

mellitus (GDM) is defined

as any degree of glucose

intolerance with onset or

--- Content provided by‌ FirstRanker.com ---

first recognition during

pregnancy .

--- Content provided by FirstRanker.com ---

Gestational diabetes is caused

when the insulin receptors do

not function properly.

--- Content provided by⁠ FirstRanker.com ---

GDM Leads to perinatal

complications.

--- Content provided by‌ FirstRanker.com ---

GDM Increases risk to suffer from

DM in later life.
Perform a diagnostic oral

--- Content provided by​ FirstRanker.com ---

glucose tolerance test

(OGTT) without prior

plasma or serum glucose

--- Content provided by​ FirstRanker.com ---

screening.

Sample drawn after 100-gram glucose drink (glucose

--- Content provided by‌ FirstRanker.com ---

load)

Time of Sample Collection

Target LEVEL

--- Content provided by⁠ FirstRanker.com ---

Fasting* (prior to glucose load)

95 mg/dL (5.3

--- Content provided by⁠ FirstRanker.com ---

mmol/L)

1 hour after glucose load

180 mg/dL (10.0 mmol/L)

--- Content provided by‍ FirstRanker.com ---

2 hours after glucose load

155 mg/dL (8.6 mmol/L)

--- Content provided by FirstRanker.com ---

3 hours after glucose load*

140 mg/dL (7.8 mmol/L)

INDICATION: If two or more values meet or exceed the

--- Content provided by​ FirstRanker.com ---

target level, gestational diabetes is diagnosed.
Women with GDM has large

gestational age (macrosomic)

--- Content provided by FirstRanker.com ---

Infants born to mothers with

untreated GDM has following

--- Content provided by​ FirstRanker.com ---

complications:

vHigh birth weight ( < 4 kg)
vRespiratory Distress syndrome
vHypoglycemia

--- Content provided by‍ FirstRanker.com ---

v Hypocalcaemia
v Hyperbilirubinemia
Remember that women

diagnosed with GDM can

--- Content provided by‍ FirstRanker.com ---

develop diabetes later onn in

their life.

--- Content provided by⁠ FirstRanker.com ---

Hence they are advised to

undergo annual screening to

enable early diagnosis or to rule

--- Content provided by FirstRanker.com ---

out the condition.

Risk Factors to Develop DM
The development of type 2 diabetes

--- Content provided by‌ FirstRanker.com ---

is caused by a combination of

lifestyle and genetic factors.

--- Content provided by​ FirstRanker.com ---

While some are under personal

control, such as diet and obesity.

Others, such as increasing age,

--- Content provided by‌ FirstRanker.com ---

female gender, and genetics are

not under personal control.

--- Content provided by⁠ FirstRanker.com ---

A lack of sleep has been

linked to type 2

diabetes. This is believed

--- Content provided by‍ FirstRanker.com ---

to act through its effect

on metabolism.
The nutritional status of a

--- Content provided by⁠ FirstRanker.com ---

mother during fetal

development may also play a

--- Content provided by​ FirstRanker.com ---

role, with one proposed

mechanism being that of

altered DNA methylation.

--- Content provided by FirstRanker.com ---

A number of lifestyle factors are known to

be important to the development of type 2

--- Content provided by​ FirstRanker.com ---

diabetes, including:

Urbanization
Stress
Obesity(defined by a body mass index of

--- Content provided by FirstRanker.com ---

greater than thirty)

Excess body fat
Lack of physical activity/Lack of exercise

--- Content provided by FirstRanker.com ---

is believed to cause 7% of DM cases.
Dietary Factors

Very poor diet increases

--- Content provided by‌ FirstRanker.com ---

risk of DM.

Very excess consumption of

--- Content provided by⁠ FirstRanker.com ---

sugar-sweetened drinks in

excess is associated with an

increased risk of DM.

--- Content provided by‌ FirstRanker.com ---

Eating lots of white rice

appears to also play a role in

--- Content provided by FirstRanker.com ---

increasing risk of DM.


The type of fats in the diet are

--- Content provided by​ FirstRanker.com ---

also important:

Dietary Saturated fats and

trans fatty acids increases

--- Content provided by FirstRanker.com ---

the risk of DM.

Dietary Polyunsaturated

--- Content provided by​ FirstRanker.com ---

and monounsaturated fat

decreasing the risk of DM.
Biochemical Alterations In DM

--- Content provided by​ FirstRanker.com ---

In Type -1 Diabetes

mellitus there is

destruction of beta cells

--- Content provided by⁠ FirstRanker.com ---

of islets of Langerhans

which leads to absolute

--- Content provided by‍ FirstRanker.com ---

deficiency of insulin.
In Type -2 Diabetes

mellitus membrane

--- Content provided by⁠ FirstRanker.com ---

Glucose transporter

GluT4 is reduced which

leads to insulin resistance.

--- Content provided by‍ FirstRanker.com ---

Metabolism Deranged In DM

Diabetes mellitus chiefly alters and

--- Content provided by FirstRanker.com ---

affects Carbohydrate metabolism

which in turn affects the interdependent

?Lipid Metabolism

--- Content provided by​ FirstRanker.com ---

?Protein Metabolism
?Water and Mineral Metabolism
Diabetes mellitus exhibits

Starvation of peripheral cells

--- Content provided by‍ FirstRanker.com ---

(Scarcity In Plenty).

Chronic Persistent Hyperglycemia

--- Content provided by‍ FirstRanker.com ---

In DM

Due to low or poor/decreased Insulin

activity in Diabetes mellitus.

--- Content provided by‌ FirstRanker.com ---

Decreased uptake of blood Glucose by

peripheral tissues.

--- Content provided by FirstRanker.com ---

Underutilization Of Glucose.
Due to more/increased Glucagon

activity.

--- Content provided by‍ FirstRanker.com ---

Over production of Glucose.
Chronic persistent hyperglycemia.

Decreased Utilization of Cellular

--- Content provided by⁠ FirstRanker.com ---

Glucose In DM

As Insulin is low in its activity in DM.
There is decreased stimulation of

--- Content provided by FirstRanker.com ---

following pathways:

vDecreased Glycolysis
vDecreased TCA cycle
vDecreased Glycogenesis

--- Content provided by FirstRanker.com ---

vDecreased Lipogenesis
vDecreased HMP shunt.
Increased Lipolysis,

Gluconeogenesis and Ketogenesis

--- Content provided by FirstRanker.com ---

In Type 1 DM

Low insulin in body of DM
More Glucagon in body of DM

--- Content provided by‍ FirstRanker.com ---

Glucagon stimulates :

?Increased Lipolysis
?Increased Gluconeogenesis
?Increased Ketogenesis

--- Content provided by‌ FirstRanker.com ---

? (Incomplete Fatty acid Oxidation)

Renal Osmotic Glycosuria In DM

Blood Glucose levels when crosses renal

--- Content provided by FirstRanker.com ---

threshold value for Glucose=180 mg%.

The presence of high Glucose in renal

--- Content provided by FirstRanker.com ---

tubules exerts an osmotic effect.

Reduces reabsorption of water.
Excretion of Glucose along with water -

--- Content provided by FirstRanker.com ---

Glucosuria (Osmotic Diuresis).
Decreased Protein

Synthesis

--- Content provided by‍ FirstRanker.com ---

and

Increased Protein

Breakdown

--- Content provided by​ FirstRanker.com ---

In DM

Low insulin activity inhibits protein

--- Content provided by⁠ FirstRanker.com ---

biosynthesis and stimulates muscle

protein breakdown in a body

suffering from Diabetes Mellitus.

--- Content provided by⁠ FirstRanker.com ---

The Glucogenic Aminoacids released

from Protein breakdown produces

--- Content provided by FirstRanker.com ---

Glucose in Liver via Gluconeogenesis.

Excess Protein breakdown makes

the person emaciated and loose

--- Content provided by​ FirstRanker.com ---

weight.
Increased Serum TAG, Cholesterol

and Ketone bodies In D.M

--- Content provided by⁠ FirstRanker.com ---

Hypertriglyceridemia in DM is

due to:

--- Content provided by‌ FirstRanker.com ---

Increased Lipolysis
Decreased Lipoprotein Lipase

activity.
"Fat Burns Under The Flame Of

--- Content provided by FirstRanker.com ---

Carbohydrate"

For complete oxidation of body fat there

--- Content provided by​ FirstRanker.com ---

needs a sufficient cellular Carbohydrate

metabolism.

Low cellular Carbohydrate metabolism in

--- Content provided by FirstRanker.com ---

DM, exhibit incomplete metabolism of

Fats.

--- Content provided by FirstRanker.com ---

In Diabetes mellitus there is less

cellular Carbohydrate metabolism

Excess but incomplete fatty acid

--- Content provided by‍ FirstRanker.com ---

oxidation

More production of Ketone bodies

--- Content provided by FirstRanker.com ---

which are partial oxidized products

of fat metabolism.
More deficiency of Insulin.
More deprivation in cellular Glucose

--- Content provided by‍ FirstRanker.com ---

metabolism.

More incomplete/partial fat oxidation.
More Ketone bodies production.

--- Content provided by⁠ FirstRanker.com ---

Accumulation of Ketone bodies in

blood- Ketonemia.

Ketone bodies excreted in Urine-

--- Content provided by‍ FirstRanker.com ---

Ketonuria.

Uncontrol ed DM shows Ketosis

--- Content provided by⁠ FirstRanker.com ---

Uncontrolled Diabetes Mellitus is a

serious condition of DM.

Very low Insulin activity.

--- Content provided by FirstRanker.com ---

Very deranged metabolic activity.
Ketonemia + Ketonuria =Ketosis
Kassumals breathing-Acetone Breath.
Acidosis-Ketoacidosis.
Diabetic Ketoacidosis.

--- Content provided by​ FirstRanker.com ---

Water Electrolyte and Acid Base

Imbalance In DM

--- Content provided by‍ FirstRanker.com ---

Osmotic Diuresis in Diabetes Mellitus
Water Loss- Dehydration.
Electrolyte Loss
Ketoacidosis- Acid Base Imbalance.

--- Content provided by‍ FirstRanker.com ---

Clinical Manifestations Of DM

Polyuria - Osmotic Diuresis.

--- Content provided by‍ FirstRanker.com ---

Polydypsia - Thirst (Due to Dehydration).
Polyphagia ? Cellular Starvation ? (Stimulate Hunger centre)
Weakness
Lethargy
Weight Loss.

--- Content provided by‍ FirstRanker.com ---

In serious conditions Coma.
Other symptoms that are commonly

present at diagnosis include:

--- Content provided by‌ FirstRanker.com ---

A history of blurred vision
Itchiness and Burning sensation.
Peripheral neuropathy
Recurrent vaginal infections, and

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fatigue.

Fatty Liver is noted in Type 2

Diabetes mellitus

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Increased influx of fatty acids in

Liver.

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Decreased VLDL formation in

Liver.

Decreased mobilization of lipids

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out from Liver.
Increased Protein Glycation in DM

Due to increased circulating blood

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Glucose.

There is increased glycation of

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body proteins.

This interferes normal function

and turn over of Proteins.

--- Content provided by⁠ FirstRanker.com ---

Glycation of Hemoglobin (HbA1c),

affects oxygen transport.

--- Content provided by‌ FirstRanker.com ---

Glycation of Albumin affects its

transport function.

Glycation of Apolipoprotein ?B ,

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affects LDL metabolism and increases

atherogenesis.

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Decreases elasticity of blood vessels.
Advanced Glycation

End(AGE) Products

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increases free radical

generation.

Enhanced Oxidative Stress

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in Diabetes mellitus.

Complications

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Of

Diabetes Mel itus
Individual suffering from

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Diabetes mellitus with poor

Glucose control for many

years develop from its

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Complications.

A person with Diabetes

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mellitus with good

control of his blood

Glucose is at low risk for

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complications of DM.
Diabetes mellitus

developed with serious

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complications, making it

a dreadful disease.

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Causes for DM Complications:

High Glucose in blood circulation

and body fluids, exerts high osmotic

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effect in blood vessels and renal

tubules.

--- Content provided by‌ FirstRanker.com ---

Osmotic Diuresis in renal tubules.
High Sorbitol(Reduced form of

Glucose) accumulates in eyes and

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causes Cataract.
Poor energy supply to

tissues make the organ

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system weak.

Defective Immune System.
More susceptible and

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compatible environment for

bacterial growth.

High circulation of blood lipids-

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hyperlipidemias increases risk of

Atherosclerosis.

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High levels of Ketone bodies in

blood and urine- Ketosis.
Long standing complications

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develop in insulin independent

tissues like

Brain ( Brain Dysfunctions and Stroke)

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Erythrocytes ( Low Oxygen Transport and

Unloading of Oxygen)

Eye Lens ( Diabetic Cataract)

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Peripheral Nerves (Diabetic Neuropathy)
Kidney (Diabetic Nephropathy)
Liver (Fatty Liver)

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Delayed Complications Of DM

Cardio Vascular Disorders

Atherosclerosis

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Myocardial Infarction ( Painless MI Attack)

Retinopathy
Cataract
Stroke

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Autonomic and Sensory Motor Dysfunction
Nephropathy
Foot Ulcers ?Gangrene
Type 2 Diabetes is typically a

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chronic disease associated

with a ten-year-shorter life

expectancy.

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Two to four times the

risk of cardiovascular

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disease, including

ischemic heart disease

and stroke in persons

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suffering from DM.
20-fold increase in

lower limb

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amputations, and

increased rates of

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hospitalizations.

In the developed world, and

increasingly elsewhere, type

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2 Diabetes is the largest

cause of non traumatic

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blindness and kidney

failure.

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It has also been associated with

an increased risk of neurological

disorders:

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Cognitive dysfunction and

dementia through disease

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processes such as

Alzheimer's disease and

vascular dementia.

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Other complications

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include:

Sexual dysfunction
Frequent infections
Acute Complication Of DM

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Diabetic Ketoacidosis
(Type 1DM)
Hyper Osmolar Nonketotic Coma.
(Type 2 DM,BGL> 900mg%)

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People with type 2 diabetes

mellitus may rarely present with

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Nonketotic Hyperosmolar coma

(a condition of very high blood

sugar associated with a

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decreased level of consciousness

and low blood pressure)
Diagnosis Of Diabetes Mellitus

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Urine Analysis

Glucose ?
Semi Quantitative Benedict's Test- Checks

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Glucosuria.

Ketone Bodies-
Rothera's Test- Checks Ketonuria.

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Blood Glucose Estimation:

GOD -POD Method.

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Fasting Blood Glucose
Post Prandial Blood Glucose

Diabetic cut off for DM is 126mg%

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in the fasting sample on two

different occasions.

Glucose

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Tolerance Test

(GTT)
Diagnostic Tests to assess

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Long term complications of

Diabetes mel itus:

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? Blood Urea
? Serum Creatinine
? Urinary Protein
? Microalbuminuria
( 300 mg/24 hr of urine)

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? Urinary Albuminuria > 300 mg/day is most

diagnostic for Diabetic Nephropathy.
Lipid Profile-

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Serum TAG
Serum Cholesterol-
Serum LDL and HDL
Results of Lipid profile assess the

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risk of macrovascular complications

CVD in Diabetes Mellitus.

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Diagnostic Tests

To Assess

Long Term And Short Term

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Glucose Control
Estimation of Glycosylated

Hemoglobin (HbA1c)

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Gives index of Glucose control

in DM in last 4-6 weeks.

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(Half life of RBC's 120 days).

Methods to measure Glycated

Hemoglobin:

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Methods based on structural

differences:

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Immunoassays
Affinity Chromatography

Methods based on charge differences:

--- Content provided by‌ FirstRanker.com ---

Ion exchange Chromatography
Isoelectric focusing
HPLC

--- Content provided by⁠ FirstRanker.com ---

Fructosamine ? Quantitation

of Glycosylated Proteins.

Gives index of Glucose control

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in DM in last 2-3 weeks.

( Half life of Albumin 20 days).
Estimation of Blood

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Insulin levels
Islet Autoantibodies
Insulin Autoantibodies

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Self Monitoring Of Glucose

In cases of Type 1 D M patients
For tight blood Glucose control
To minimize complications of DM.

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By Accu Check-Glucometer
By Uri Stics -
Glucostics , Albustics , Ketostics.
Treatment Of DM

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Diabetes mellitus is not a curable

disease.

Treatment or Management of

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Diabetes mellitus is

Controlling the blood Glucose

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levels within normal range.

Management Of IDDM

Diet Control- Foods with low

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Glycaemic Index.

Weight to be improved- Good

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Protein diet.

Insulin therapy- Adjust Insulin

dose w.r.t BGL.

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Monitoring of the patients

during Insulin therapy:

Insulin therapy lowers serum

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potassium levels (Hypokalemia)

check and correct for it.

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High doses of Insulin may lead to

hypoglycemia have a check.

Management Of NIDDM

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Diet Control.
Exercise to loose weight.
Use of Hypoglycemic Drugs
Hypoglycemic Drugs

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Sulfonylureas- Glipizide (Glucotrol),

Glyburide (Diabeta), Tolazamide (Tolinase)

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Meglitinides-Replaglinide (Prandin)
Biguanides- Metformin (Glucophage)
Butamide
Thiazolidinediones (TZDs)-Rosiglitazone

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(Avandia)

Incretin mimetic- Exenatide

Oral Medication Mechanisms:

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Increases insulin production.

Improves insulin receptor

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sensitivity.

Inhibits Gluconeogenesis.

Inhibits Carbohydrate

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absorption from GIT.
Prevention Of Diabetes Mellitus

Onset of Type 2 Diabetes can be

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delayed or prevented through:

Proper nutrition ? Balanced diet
Diet high in green leafy vegetables

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Limiting the intake of sugary

drinks

Regular Exercise

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Balanced lifestyle may

reduce the risk by over

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half

Avoid stressful life- being

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Spiritual,Organized and

Ethical.
Glycosuria

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Glycosuria is a

pathological condition

Detectable amount of

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sugar is excreted out

through urine.

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Causes For Glycosuria:

Increased levels of blood sugar

over their renal threshold values.

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Defect in renal tubules lowering

the renal threshold values of sugars.

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Renal threshold value for

Glucose = 180 mg%.
Types Of Glycosuria

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Glucosuria (Most Common)
Fructosuria
Galactosuria
Pentosuria

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Diabetic/ Hyperglycemic Glycosuria
Alimentary Glycosuria
(GIT absorption defect)
Emotional Glycosuria
(In anxiety, stress, anger)

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Renal Glycosuria
(Renal tubular defect, low renal threshold value)
Detection And Confirmation Of

Glycosuria:

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Semi Quantitative

Benedicts Test on

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Urine Specimen.

Observations Of Semi Quantitative

Benedicts Test

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No change in test color

Negative Test-

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No Glycosuria

Green color Precipitate 0.5 % Glucose

(Cu2O)

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present

Yellow color Precipitate

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1% Glucose

present

Orange color Precipitate

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1.5 % Glucose

present

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Red color Precipitate

2% or more

Glucose present.

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Glucose Tolerance Test

(GTT)

What Is GTT?

--- Content provided by​ FirstRanker.com ---

Glucose Tolerance Test (GTT)
Is a special investigation
Carried out in a Clinical

Biochemistry Laboratory

--- Content provided by‌ FirstRanker.com ---

To check the bodies tolerance

towards a high dose (75gm) of

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Glucose in a fasting condition.

Normal Tolerance ?

v Normal Blood Glucose

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v No Glycosuria
Decreased Tolerance ?

v Increased Blood Glucose

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v May have Glycosuria

Increased Tolerance ?

v Decreased blood Glucose

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v No Glycosuria
Indications Of GTT

OR

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When GTT Is Prescribed ?

In a case which is unclear-

Has symptoms of Diabetes

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Mellitus but normal BGL.

To diagnose Gestational

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DM(GDM) during pregnancy.

To find out severity of DM
To rule out renal Glycosuria.
Types Of GTT

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Oral GTT

Oral dosage of Glucose given

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during test.

Intravenous GTT

In GIT disordered persons,

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Glucose dose is infused

intravenously.
Mini GTT

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The duration of GTT is reduced to 1

? hrs.

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Corticosteroid Stressed GTT

GTT is tested after dosage of

corticosteroids.

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Preparation of a Person

for GTT

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OR

Advice Given To a Person

Prior to GTT

--- Content provided by‌ FirstRanker.com ---

A week prior to the appointed date for

GTT, the person is advised for:

Eat normal Carbohydrate diet

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Do Not fast or starve

Do no strenuously exercise

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Drink no Alcohol

Take no medications

The person is advised to

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come in fasting

condition (10-12 hrs fast)

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on the test date.
Procedure Of Oral GTT

Collect a fasting blood

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and urine specimen

from the person

undergoing GTT.

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Label the collected

fasting samples (F)
Note the time

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Give an oral dose of Glucose

75 gm with 250 ml water/1.5

gm per kg body wt.

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May flavor with lemon to

avoid vomiting.

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From the time of dosage with

an interval of 30 minutes collect

the blood and urine specimens

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up to 2 1/2 hrs or 150 minutes.

Label each collected specimen.
Analyze all the collected

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specimens.
Blood specimens are analyzed

to estimate Glucose

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concentration (Using GOD-

POD method).

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Urine specimens are checked

for qualitative

presence/absence of Glucose

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(Benedicts Test)

Record the readings of

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blood Glucose for every

specimen

Plot a GTT curve on

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graph paper and interpret

the results.

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Plot a GTT Curve

Specimens

--- Content provided by‍ FirstRanker.com ---

Blood

Urine

Glucose

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Glucose

Fasting

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75 mg%

Absent

30 minutes

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100 mg%

Absent

--- Content provided by⁠ FirstRanker.com ---

60 minutes

120 mg%

Absent

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90 minutes

145 mg%

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Absent

120 minutes

1 20 mg%

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Absent

150 minutes

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85 mg%

Absent
Plot a GTT Curve

--- Content provided by‌ FirstRanker.com ---

Specimens

Blood Glucose Urine Glucose

Fasting

--- Content provided by‍ FirstRanker.com ---

160 mg%

Absent

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30 minutes

170 mg%

Absent

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60 minutes

200 mg%

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Present

90 minutes

240 mg%

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Present

120 minutes

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230 mg%

Present

150 minutes

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180 mg%

Present

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Question

Why there is need of

continuous and uninterrupted

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Glycolysis in RBC's?

To maintain RBC membrane

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integrity and avoid destruction

and lysis of RBC's.

RBC membrane structure

--- Content provided by‍ FirstRanker.com ---

The RBC membrane

Located in the

membrane are

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proteins that

function as cationic

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pumps.

The RBC maintains its volume and

water homeostasis by controlling the

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intracellular concentrations of Na+ and

K+ via these cationic pumps which

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require ATP.

ATP is also required in the Ca++

pump system that prevents

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excessive intracellular build-up of

Ca++.
In ATP depleted cells there is

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an intracellular build up of

Na+ and Ca++ and a loss of K+

--- Content provided by‌ FirstRanker.com ---

and water.

This leads to dehydrated, rigid

cells that are destructed/ lysed

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and culled by the spleen.

Any abnormality that

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increases membrane

permeability or alters

cationic transport may

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lead to decreased RBC

survival.
The major peripheral protein in

--- Content provided by‌ FirstRanker.com ---

RBC's is Spectrin

It binds with other peripheral

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proteins such as Actin to form a

skeleton of microfilaments on the

inner surface of the membrane.

--- Content provided by‌ FirstRanker.com ---

This strengthens the membrane

and gives it its elastic properties.

--- Content provided by‍ FirstRanker.com ---

For Spectrin to participate in

this interaction, it must be

phosphorylated by a protein

--- Content provided by FirstRanker.com ---

kinase that requires ATP.

Thus, a decrease in ATP

--- Content provided by‌ FirstRanker.com ---

Decreased Phosphorylation

of Spectrin.
Unphosphorylated

--- Content provided by FirstRanker.com ---

Spectrin can no longer bind

to Actin to give the

membrane its elastic

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properties.

This then leads to a loss in

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membrane deformability and

a decreased RBC survival time.

Pasteur And Crabtree Effects

--- Content provided by FirstRanker.com ---

Study findings of Glucose

metabolism (Catabolism)

in Yeast Saccharomyces

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cerevisiae under both

aerobic and anaerobic

--- Content provided by​ FirstRanker.com ---

condition.

Experimental findings of Glucose

metabolism in Yeast cells in

--- Content provided by⁠ FirstRanker.com ---

different concentrations of:

vOxygen
vSugar

--- Content provided by‍ FirstRanker.com ---

Yeast's are ubiquitous

unicellular fungi.

Most yeast cells are of

--- Content provided by‌ FirstRanker.com ---

facultative fermentative.

Types of Yeast

--- Content provided by‌ FirstRanker.com ---

Non fermentative ?Has exclusively

respiratory metabolism (aerobic), not

capable of alcohol fermentation.

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Obligate fermentative- Natural respiratory

mutants metabolize Glucose only through

--- Content provided by‍ FirstRanker.com ---

alcoholic fermentation.

Facultative fermentative- Fully respiratory

or fermentative metabolism or both

--- Content provided by FirstRanker.com ---

respiratory and fermentative mechanism.
Yeast Sugar Metabolism

Yeast sugar metabolism

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depends on:

Growth condition

--- Content provided by​ FirstRanker.com ---

qType and concentration of

Sugar

qOxygen concentration

--- Content provided by⁠ FirstRanker.com ---

Metabolic flux occurs on the

Pyruvate branch point.

--- Content provided by​ FirstRanker.com ---

Pyruvate is oxidized via TCA in

aerobic condition.

Pyruvate is reduced/ fermented

--- Content provided by​ FirstRanker.com ---

to Lactate or ethanol in

anaerobic condition.

--- Content provided by‌ FirstRanker.com ---

Pasteur effect

Word origin: named after its

--- Content provided by‌ FirstRanker.com ---

discoverer Louis Pasteur.
In 1861 Louis Pasteur figured out
In the absence of oxygen, yeast

consumes more glucose than in

--- Content provided by​ FirstRanker.com ---

the presence of oxygen.

A phenomenon that has become

--- Content provided by FirstRanker.com ---

known as Pasteur effect in the

literature.

Pasteur effect explains the

--- Content provided by‌ FirstRanker.com ---

inhibiting effect of oxygen

on the process of

--- Content provided by FirstRanker.com ---

fermentation.
Oxygen inhibits Glycolysis.
Oxygen limits the use of Glucose.
In aerobic Glycolysis more ATP

--- Content provided by​ FirstRanker.com ---

produced inhibits PFK of Glycolysis.

In aerobic condition no fermentation

occurs.

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In aerobic condition there is no

production of Ethanol/Lactate.

--- Content provided by‍ FirstRanker.com ---

This shift from slow aerobic to rapid

anaerobic consumption of glucose was

first noted by Pasteur.

--- Content provided by⁠ FirstRanker.com ---

This shift also happens anytime you

are unable to provide oxygen to your

--- Content provided by‍ FirstRanker.com ---

own mitochondria- they consume

Glucose faster in an attempt to produce

ATP via the less efficient fermentation

--- Content provided by​ FirstRanker.com ---

to lactate, and lactic acid accumulates

in your muscles.
He found that aerating yeasted broth

--- Content provided by​ FirstRanker.com ---

caused the yeast cell growth increased

while fermentation rate decreased.

--- Content provided by‍ FirstRanker.com ---

A switch from anaerobic to aerobic

conditions results in the decrease in

the rate of carbohydrate breakdown in

--- Content provided by FirstRanker.com ---

yeasts.

Citrate and ATP, allosteric inhibition

--- Content provided by‍ FirstRanker.com ---

of the PFK 1 enzyme explains the

Pasteur effect.

Pasteur effect is defined as

--- Content provided by⁠ FirstRanker.com ---

inhibition of fermentation

pathway by respiration

--- Content provided by FirstRanker.com ---

(Oxygen).

Oxygen inhibits

fermentation(Ethanol/Lactate

--- Content provided by‍ FirstRanker.com ---

production) and reduces the

rate of Glycolysis.
Fermentation occurs

--- Content provided by‌ FirstRanker.com ---

in anaerobic conditions.

Later studies reported several misinterpretations

--- Content provided by FirstRanker.com ---

related to the results of Pasteur effect.

Stated that results of Pasteur were an artefact due

to anaerobic growth impairment.

--- Content provided by‌ FirstRanker.com ---

Anaerobic fermentation occurred in yeast entered

in stationary or resting phase.

--- Content provided by‍ FirstRanker.com ---

Anaerobic fermentation occurred in sugar limiting

continuous culturing and at resting cell condition.

Production of alcohol occurs when cells are in

--- Content provided by‌ FirstRanker.com ---

growth / lag phase.
In presence of high

concentration of Glucose ,the

--- Content provided by‍ FirstRanker.com ---

Pasteur effect does not work.

Under this condition the

--- Content provided by‍ FirstRanker.com ---

degradation of Glucose is via

fermentation to produce

ethanol in aerobic condition.

--- Content provided by FirstRanker.com ---

Crabtree Effect
Named after the English

Biochemist

--- Content provided by‌ FirstRanker.com ---

Herbert Grace Crabtree.

Crabtree effect is

--- Content provided by‌ FirstRanker.com ---

the converse of the

Pasteur effect.
The Crabtree effect(1929) describes

--- Content provided by⁠ FirstRanker.com ---

the phenomenon whereby the

Yeast, Saccharomyces cerevisiae,

produces ethanol (alcohol)

--- Content provided by⁠ FirstRanker.com ---

aerobically in the presence of high

external glucose concentrations

--- Content provided by​ FirstRanker.com ---

rather than producing biomass via

the Tricarboxylic acid cycle.

Crabtree effect defines

--- Content provided by‍ FirstRanker.com ---

occurrence of alcoholic

fermentation under aerobic

--- Content provided by⁠ FirstRanker.com ---

conditions.

Saccharomyces cerevisiae

catabolize Glucose mainly by

--- Content provided by FirstRanker.com ---

fermentative process.
When oxygen supply is kept constant

and Glucose concentration is increased,

--- Content provided by FirstRanker.com ---

the oxygen consumption by cells falls.

Cells with high rate of Glycolysis

--- Content provided by‍ FirstRanker.com ---

consumes pi and NAD+ which limits

their availability to operate oxidative

phosphorylation.

--- Content provided by FirstRanker.com ---

Here ETC/ oxidative phosphorylation

decreases and that decrease oxygen

--- Content provided by​ FirstRanker.com ---

consumption.

At high Glucose concentration the rate

of aerobic fermentation is also

--- Content provided by‌ FirstRanker.com ---

increased.

At high concentration of Glucose there

--- Content provided by FirstRanker.com ---

is inhibition of synthesis of ETC

enzymes by high fermentation rates.

High rate of Glycolysis reduces the

--- Content provided by‌ FirstRanker.com ---

respiratory chain and induces

fermentation to produce alcohol.

--- Content provided by‍ FirstRanker.com ---

Catabolite repression of ETC enzymes.

Mechanisms Explaining

Crabtree Effect

--- Content provided by‍ FirstRanker.com ---

v Catabolite Repression
v Catabolite Inactivation
v Limited Respiration

--- Content provided by FirstRanker.com ---

Capacity

Catabolite Repression

When Glucose/ initial

--- Content provided by FirstRanker.com ---

product of Glucose

metabolism suppress the

--- Content provided by‍ FirstRanker.com ---

synthesis of various

enzymes of respiration( Still

unclear).

--- Content provided by⁠ FirstRanker.com ---

High concentration of

sugar disrupts the

structure of yeast

--- Content provided by‌ FirstRanker.com ---

mitochondria.

Respiration is stopped

--- Content provided by​ FirstRanker.com ---

Ethanol fermentation

occurs.

Catabolite Inactivation

--- Content provided by⁠ FirstRanker.com ---

Glucose in high

concentration inhibits the

--- Content provided by​ FirstRanker.com ---

key enzymes of respiratory

track.
Crabtree effect in Yeast

--- Content provided by FirstRanker.com ---

cell can be observed when

the growth medium

containing Glucose in

--- Content provided by‌ FirstRanker.com ---

concentration above 5mM.

Increasing concentrations of Glucose

--- Content provided by​ FirstRanker.com ---

accelerates Glycolysis (the breakdown

of glucose) which results in the

production of appreciable amounts of

--- Content provided by‌ FirstRanker.com ---

ATP through substrate-level

phosphorylation.

--- Content provided by FirstRanker.com ---

This reduces the need of oxidative

phosphorylation done by the TCA cycle

via the electron transport chain and

--- Content provided by​ FirstRanker.com ---

therefore decreases oxygen

consumption.
The effect can be easily

--- Content provided by FirstRanker.com ---

explained, as the yeast being

facultative anaerobes can

--- Content provided by​ FirstRanker.com ---

produce energy using two

different metabolic pathways.

While the oxygen concentration

--- Content provided by​ FirstRanker.com ---

is low, the product of Glycolysis,

(Pyruvate), is turned into ethanol

--- Content provided by‍ FirstRanker.com ---

and carbon dioxide, and the energy

production efficiency is low

(2 moles of ATP per mole of

--- Content provided by​ FirstRanker.com ---

glucose).
If the oxygen concentration grows,

Pyruvate is converted to acetyl CoA

--- Content provided by‍ FirstRanker.com ---

that can be used in the citric acid cycle,

which increases the efficiency to 32

--- Content provided by​ FirstRanker.com ---

moles of ATP per mole of Glucose.

Therefore, about 15 times as much

glucose must be consumed

--- Content provided by‍ FirstRanker.com ---

anaerobically as aerobically to yield the

same amount of ATP.

--- Content provided by⁠ FirstRanker.com ---

Under anaerobic

conditions, the rate of

Glucose metabolism is

--- Content provided by⁠ FirstRanker.com ---

faster, but the amount of

ATP produced (as already

--- Content provided by‍ FirstRanker.com ---

mentioned) is smaller.
When exposed to aerobic

conditions, the ATP production

--- Content provided by FirstRanker.com ---

increases and the rate of Glycolysis

slows, because the ATP produced

acts as an allosteric inhibitor for

--- Content provided by‌ FirstRanker.com ---

Phosphofructokinase 1, the third

enzyme in the Glycolysis pathway.

--- Content provided by‍ FirstRanker.com ---

So, from the standpoint of ATP

production, it is advantageous

for yeast to undergo Krebs Cycle

--- Content provided by‌ FirstRanker.com ---

in the presence of oxygen, as

more ATP is produced from less

--- Content provided by‌ FirstRanker.com ---

Glucose.
When Glucose concentration is high in aerobic

condition:

--- Content provided by​ FirstRanker.com ---

Yeast fermentation in aerobic condition has limited

capacity.

High Glucose concentration

--- Content provided by‍ FirstRanker.com ---

Increases Glycolysis
Increased Pyruvate concentration
Limits the yeast to use Pyruvate in line of TCA and

oxidative phosphorylation.

--- Content provided by FirstRanker.com ---

Pyruvate is fermented to Ethanol.

When Glucose concentration is

--- Content provided by⁠ FirstRanker.com ---

high in anaerobic condition:

Yeast fermentation in anaerobic

condition has unlimited

--- Content provided by FirstRanker.com ---

capacity.

Use all Pyruvate generated from

--- Content provided by⁠ FirstRanker.com ---

Glycolysis to Ethanol

unlimitedly.
Crabtree phenomena occurs

--- Content provided by FirstRanker.com ---

in tumor cells where cell is in

the aerobic condition

metabolizes Glucose

--- Content provided by FirstRanker.com ---

excessively via Glycolysis and

produces Lactate.

--- Content provided by‍ FirstRanker.com ---

QUESTIONS
I) Long Answer Questions.

Q.1 Give principle carbohydrates

--- Content provided by FirstRanker.com ---

present in the diet & its rich

food sources. Describe the

digestion & absorption of

--- Content provided by‍ FirstRanker.com ---

different carbohydrate forms.

Q.2 Define Glycolysis. Describe

--- Content provided by​ FirstRanker.com ---

reactions, Energetics, significance,

regulation of Glycolysis.

OR

--- Content provided by‍ FirstRanker.com ---

Describe E.M.P. pathway

(Conversion of Glucose to Pyruvate).
Q.3 Describe Glycogen metabolism

--- Content provided by​ FirstRanker.com ---

& its regulation.

OR

--- Content provided by‍ FirstRanker.com ---

Describe Glycogenesis and its

regulation

Describe Glycogenolysis and its

--- Content provided by⁠ FirstRanker.com ---

regulation.

Q.4 Describe T.C.A. cycle/Kreb's

--- Content provided by‌ FirstRanker.com ---

cycle/Amphibolic pathway/Common

metabolic pathway.

OR

--- Content provided by⁠ FirstRanker.com ---

How Acetyl-CoA is oxidized in the

body & give its significance.

--- Content provided by FirstRanker.com ---

Q.5 Describe H.M.P. Shunt & Give its

significance.

OR

--- Content provided by​ FirstRanker.com ---

Describe Pentose Phosphate Pathway.
Q.6 Define Gluconeogenesis. Describe

the reactions of Gluconeogenesis.

--- Content provided by​ FirstRanker.com ---

State the fate of the Glucogenic

precursors .How Gluconeogenesis is

--- Content provided by‌ FirstRanker.com ---

regulated.

Q.7 Describe Diabetes Mellitus with

respect to clinical types, causes,

--- Content provided by‌ FirstRanker.com ---

biochemical alterations, clinical

manifestations, diagnosis &

--- Content provided by⁠ FirstRanker.com ---

management.

Q.8 Homeostasis of blood glucose

level by hormonal & metabolic factors.

--- Content provided by‍ FirstRanker.com ---

II) Short Notes

Lactose Intolerance

--- Content provided by‍ FirstRanker.com ---

Dietary cellulose & its importance.
Role of Insulin in Carbohydrate

metabolism.

--- Content provided by⁠ FirstRanker.com ---

Fates of dietary Glucose entered in the

Liver cells.

Difference between Insulin & Glucagon.

--- Content provided by FirstRanker.com ---

Glycogen storage disorders/Inherited

disorders of Glycogen Metabolism.

--- Content provided by FirstRanker.com ---

Difference between EMP & HMP

pathways.

G-6 P. D. deficiency.

--- Content provided by FirstRanker.com ---

Uronic Acid Pathway & its significance.
Metabolic fate of Fructose
Rapaport Leubering

Cycle/Glycolysis in Erythrocytes.

--- Content provided by⁠ FirstRanker.com ---

Oxidative Decarboxylation of

Pyruvate/Pyruvate Dehydrogenase

--- Content provided by‍ FirstRanker.com ---

Complex.

Glycogenolysis in Muscles & Liver.
Cori's Cycle/Metabolism of Lactate.

--- Content provided by‌ FirstRanker.com ---

Metabolic fate of Galactose
Galactosemia.
Glycosuria.
Difference between Hyperglycemia

--- Content provided by‌ FirstRanker.com ---

& Hypoglycemia

Glucose Tolerance Test.
Inborn errors of Carbohydrate

--- Content provided by⁠ FirstRanker.com ---

Metabolism.

Glucose Transporters
Glucose Alanine Cycle
Glycaemic Index of Foods and

--- Content provided by FirstRanker.com ---

their importance

G: N /D:N ratio
Differentiate between IDDM

--- Content provided by​ FirstRanker.com ---

and NIDDM

Role of HMP Shunt in

--- Content provided by⁠ FirstRanker.com ---

Erythrocytes.

NADPH+H+ requiring enzymes.
Site & significance of Rapaport

--- Content provided by‍ FirstRanker.com ---

Leubering cycle.
Short Answer Questions

--- Content provided by​ FirstRanker.com ---

Define substrate level phosphorylation.

Give examples of it.

Calculate the Energetics of Glycolysis

--- Content provided by‌ FirstRanker.com ---

in Aerobic & Anaerobic condition.

Write formation and fates of Pyruvate

--- Content provided by FirstRanker.com ---

in the body.

Calculate the Energetics of complete

oxidation of 1 glucose molecule.

--- Content provided by‌ FirstRanker.com ---

Give the Regulatory enzymes of

following pathways -

--- Content provided by FirstRanker.com ---

Glycolysis
HMP Shunt
Gluconeogenesis
Glycogenesis
Glycogenolysis

--- Content provided by​ FirstRanker.com ---

Glycosidases & their

role/Glycosidases their action &

products in GIT.

--- Content provided by FirstRanker.com ---

Enumerate disorders of

carbohydrate metabolism with

--- Content provided by FirstRanker.com ---

respect to biochemical defect &

biochemical alterations.

Write the enzymes &

--- Content provided by⁠ FirstRanker.com ---

coenzymes of PDH and KDH

complex.

--- Content provided by⁠ FirstRanker.com ---

Enumerate the diagnostic tests

for Diabetes mellitus.

Give four factors, which

--- Content provided by​ FirstRanker.com ---

regulate blood glucose.
Write various pathways of

carbohydrate metabolism

--- Content provided by‍ FirstRanker.com ---

with respect to occurrence/

location (where), condition

--- Content provided by​ FirstRanker.com ---

(when), significance (why).

Pasteur and Crabtree effect

Case Studies

--- Content provided by⁠ FirstRanker.com ---

Case Study 1

A 58 year old obese man with

frequent urination is seen by his

--- Content provided by‍ FirstRanker.com ---

primary care physician. The

following laboratory tests were

--- Content provided by‌ FirstRanker.com ---

performed.

Random blood Glucose= 225 mg%
Urine Glucose 2+
Urine Ketones Negative

--- Content provided by‌ FirstRanker.com ---

Questions

What is probable diagnosis of this

patient?

--- Content provided by‍ FirstRanker.com ---

What other tests should be

performed to confirm this?

--- Content provided by‍ FirstRanker.com ---

After diagnosis what test should be

performed to monitor his

condition?

--- Content provided by FirstRanker.com ---

Case Study 2
An 18 yr male who had an history of

Diabetes mellitus was brought to an

--- Content provided by‌ FirstRanker.com ---

emergency department because of

excessive drowsiness , vomiting and

--- Content provided by​ FirstRanker.com ---

diarrhea .His Diabetes had been well

controlled with 40 units of Insulin daily

until several days ago . When he

--- Content provided by⁠ FirstRanker.com ---

developed excessive thirst an Polyuria.

For past three days he also had

--- Content provided by FirstRanker.com ---

headache, myalgia, and low grade fever

. Diarrhea and Vomiting began one day

ago.

--- Content provided by​ FirstRanker.com ---

Questions

What is the probable diagnosis of this

--- Content provided by⁠ FirstRanker.com ---

patient based on the data presented?

What laboratory tests should be performed

to manage this patients condition?

--- Content provided by⁠ FirstRanker.com ---

Why are urine ketones positive?
What methods are used to detect urine

ketones? Which ketone body is detected?

--- Content provided by​ FirstRanker.com ---

Case Study 3

A 14 yr old male student was seen by his

physician. His chief complaints were fatigue,

--- Content provided by​ FirstRanker.com ---

weight loss, and increase in appetite , thirst

and frequency of urination . For the past

--- Content provided by‌ FirstRanker.com ---

three to four weeks he had been excessively

thirsty and had to urinate every few hours.

He began to get up 3 to 4 times a night to

--- Content provided by​ FirstRanker.com ---

urinate . The patient has family history of

Diabetes mellitus.

--- Content provided by​ FirstRanker.com ---

Fasting Blood Glucose=160 mg%
Glycosuria and Ketonuria detected.
Questions

Based on the preceding information can this

--- Content provided by​ FirstRanker.com ---

patient be diagnosed with Diabetes

mellitus?

--- Content provided by⁠ FirstRanker.com ---

What further tests might be performed to

confirm the diagnosis?

According to ADA what criteria are

--- Content provided by‌ FirstRanker.com ---

required for the diagnosis Of Diabetes

mellitus?

--- Content provided by‍ FirstRanker.com ---

Assuming this patient has diabetes which

type would be diagnosed?

Diagnostic Criteria For DM

--- Content provided by⁠ FirstRanker.com ---

Random Blood Glucose

> 200 mg%

--- Content provided by‌ FirstRanker.com ---

+ Symptoms of DM

Fasting Blood Glucose

>126 mg%

--- Content provided by FirstRanker.com ---

Post prandial Blood Glucose > 200 mg%
Case Study 4

A 13 year old girl collapsed on a play ground

--- Content provided by​ FirstRanker.com ---

at school. When her mother was contacted

she mentioned that her daughter had been

--- Content provided by FirstRanker.com ---

loosing weight and making frequent trips to

the bathroom in the night. The emergency

squad noticed a fruity breath. On entrance

--- Content provided by‍ FirstRanker.com ---

to emergency dept her vital signs were as

follows:

--- Content provided by‌ FirstRanker.com ---

B.P -98/50
Body Temp 99 degree
Respirations Rapid
Urine PH

--- Content provided by⁠ FirstRanker.com ---

5.5

Urine Protein

Negative

--- Content provided by​ FirstRanker.com ---

Urine Glucose

4+

--- Content provided by‍ FirstRanker.com ---

Urine Ketones

Present

Blood Glucose

--- Content provided by FirstRanker.com ---

500 mg%

Blood Urea

--- Content provided by​ FirstRanker.com ---

30 mg%

Serum Creatinine

0.4 mg%

--- Content provided by​ FirstRanker.com ---

Questions

Identify the patients most likely

--- Content provided by‌ FirstRanker.com ---

type of Diabetes mellitus?

What is the cause of fruity breath?
Case Study 5

--- Content provided by‍ FirstRanker.com ---

A 28 year old woman delivered a 9.5 lb

infant .

The mothers history was incomplete

--- Content provided by‍ FirstRanker.com ---

and she claimed to have had no

medical care through her pregnancy .

--- Content provided by​ FirstRanker.com ---

Shortly after birth the infant became

lethargic and flaccid.

Blood Glucose = 25 mg%

--- Content provided by FirstRanker.com ---

Ionized Calcium= 4.9 mg%
Questions

Give the possible explanation for the

--- Content provided by‌ FirstRanker.com ---

infants large birth weight and size.

If the mother was gestational Diabetic

why was her baby hypoglycemic?

--- Content provided by‌ FirstRanker.com ---

If the mother had been monitored

during pregnancy what laboratory tests

--- Content provided by‌ FirstRanker.com ---

should have been performed?

Case Study 6
Laboratory tests were performed on a 50

--- Content provided by⁠ FirstRanker.com ---

year old lean white woman during an annual

physical examination . She has no family

history of Diabetes or any history of elevated

--- Content provided by​ FirstRanker.com ---

Glucose levels during Pregnancy.

Fasting Blood Glucose

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90 mg%

Serum Cholesterol

140 mg%

--- Content provided by‍ FirstRanker.com ---

HDL

40 mg%

--- Content provided by‍ FirstRanker.com ---

Serum Triglycerides

90 mg%

Questions

--- Content provided by‍ FirstRanker.com ---

What is probable

diagnosis of this patient?

--- Content provided by⁠ FirstRanker.com ---

Describe the proper

follow up for this patient?
Case Study 7

--- Content provided by FirstRanker.com ---

For 3 consecutive months, a fasting

Glucose and Glycosylated Hemoglobin

were performed on a patient. The result

--- Content provided by FirstRanker.com ---

are as follows:

Quarter 1 Quarter 2 Quarter 3

--- Content provided by‍ FirstRanker.com ---

Fasting 280 mg%

85 mg%

91 mg%

--- Content provided by‍ FirstRanker.com ---

Blood

Glucose

--- Content provided by⁠ FirstRanker.com ---

Hb A1c

7.8 %

15.3 %

--- Content provided by FirstRanker.com ---

8.5 %
Questions

In which quarter was the patients

--- Content provided by​ FirstRanker.com ---

Glucose the best regulated

Do the fasting Glucose and

--- Content provided by​ FirstRanker.com ---

Glycosylated Hb match? Why or

Why not?

Case Study 8

--- Content provided by FirstRanker.com ---

A 25 yr old healthy female

patient complains of dizziness

and shaking 1 hour after eating a

--- Content provided by​ FirstRanker.com ---

large heavy carbohydrate meal .

The result of random Glucose

--- Content provided by‍ FirstRanker.com ---

test performed showed 55 mg%.

However he had lost

consciousness on that occasion;

--- Content provided by⁠ FirstRanker.com ---

his mother had made him drink

a heavily sugared milk thinking

--- Content provided by‍ FirstRanker.com ---

that the child was feeling weak.

This seemed to have alleviated

symptoms.

--- Content provided by‍ FirstRanker.com ---

Questions

Identify the characteristic of

Hypoglycemia in the case

--- Content provided by‌ FirstRanker.com ---

study?

What tests should be

--- Content provided by FirstRanker.com ---

performed next to determine

the problem?

Case Study 9

--- Content provided by‌ FirstRanker.com ---

A 5 year old child was brought to the

medical OPD in a comatose state . He

had felt headache and dizziness only a

--- Content provided by FirstRanker.com ---

few hours before. His father noticed

profuse sweating and some abnormal

--- Content provided by‍ FirstRanker.com ---

behavior at that time and rushed him to

the hospital. A similar episode had

occurred two months earlier after the

--- Content provided by‌ FirstRanker.com ---

child had a glass of sugarcane juice .

Presently physical examination

--- Content provided by‌ FirstRanker.com ---

showed tachycardia and rapid

breathing . Liver was markedly

enlarged, being palpable 4 cm

--- Content provided by​ FirstRanker.com ---

below coastal margin .Blood

and urine samples were

--- Content provided by‍ FirstRanker.com ---

analyzed .
Blood glucose was 52mg% , no

other abnormality was found in

--- Content provided by FirstRanker.com ---

the test result. The child was

given intravenous dextrose to

treat hypoglycemia. He

--- Content provided by FirstRanker.com ---

responded well and the

hypoglycemia symptoms were

--- Content provided by‌ FirstRanker.com ---

promptly disappeared .

Two days later, Liver biopsy

reports revealed large

--- Content provided by‌ FirstRanker.com ---

deposits of Fructose-1-PO4

within hepatocytes.
Questions

--- Content provided by⁠ FirstRanker.com ---

What is the probable biochemical defect

in this child ? Suggest a biochemical test

--- Content provided by⁠ FirstRanker.com ---

to evaluate the above diagnosis.

Provide biochemical explanation for the

child's sign and symptoms

--- Content provided by FirstRanker.com ---

Would you expect liver function to be

normal or sluggish in this child? Give

--- Content provided by‍ FirstRanker.com ---

reason.

Suggest how to manage this condition?

Case Study 10

--- Content provided by⁠ FirstRanker.com ---

A 23 year old male developed fever

about two weeks back. He had

bouts of shivering temperature of

--- Content provided by‌ FirstRanker.com ---

40. 4 degree centigrade and started

treatment with Primaquine after

--- Content provided by​ FirstRanker.com ---

identification of the parasites in a

blood smear.

The fever subsided the next day

--- Content provided by‍ FirstRanker.com ---

the following symptoms

aggravated and he felt fatigue,

--- Content provided by‌ FirstRanker.com ---

dizziness breathlessness on

slightest exertion headache and

insomnia and paresthesia of the

--- Content provided by‍ FirstRanker.com ---

fingers and toes.
Three days later , the patient

noticed dark black coloured

--- Content provided by​ FirstRanker.com ---

urine. On examination he

showed pallor of the skin and

--- Content provided by⁠ FirstRanker.com ---

the mucous membrane, yellow

sclera . Jaundice, tachycardia(

heart rate 110/min) and systolic

--- Content provided by‌ FirstRanker.com ---

murmurs were prominent and

spleen was enlarged.

--- Content provided by​ FirstRanker.com ---

Investigations

Patients

Reference

--- Content provided by‍ FirstRanker.com ---

result

range

--- Content provided by⁠ FirstRanker.com ---

Hemoglobin

10.2 gm%

11-14 gm %

--- Content provided by‌ FirstRanker.com ---

Reticulocyte

6.3 %

--- Content provided by​ FirstRanker.com ---

Up to 2 %

count

Serum Total

--- Content provided by‌ FirstRanker.com ---

8.3 mg%

0.1 -1 mg %

--- Content provided by‍ FirstRanker.com ---

Bilirubin

Urine bile

Absent

--- Content provided by‌ FirstRanker.com ---

pigment
The red cells , on

microscopic examination ,

--- Content provided by​ FirstRanker.com ---

were found to contain small

inclusion bodies( Heinz

--- Content provided by⁠ FirstRanker.com ---

bodies).

Questions

What is the probable diagnosis?

--- Content provided by‌ FirstRanker.com ---

What type of anemia and Jaundice

developed in patient?

State the biochemical basis of the

--- Content provided by‍ FirstRanker.com ---

problem?

Which metabolic pathway is

--- Content provided by FirstRanker.com ---

affected in this disordered state?
Case Study 11

A premature infant of 2.3 kg body

--- Content provided by‌ FirstRanker.com ---

weight, born to Diabetic mother,

was shifted to nursery after the

attending of paediatrician noticed .

--- Content provided by‌ FirstRanker.com ---

The noted symptoms were muscle

twitching ,tremors profuse

--- Content provided by FirstRanker.com ---

sweating.
Soon after, the infant had

convulsions and lapsed into

--- Content provided by⁠ FirstRanker.com ---

comatose state. Blood analysis

showed .

Blood Glucose =38 mg%

--- Content provided by‌ FirstRanker.com ---

Questions

What is the probable diagnosis?
Why there is muscle twitching in

--- Content provided by⁠ FirstRanker.com ---

infant?

Could the Diabetes in mother is

--- Content provided by⁠ FirstRanker.com ---

responsible for the infants

condition?

Why there is loss of consciousness?

--- Content provided by FirstRanker.com ---

THANKYOU

Quantitative Estimation Of

Blood Glucose

--- Content provided by⁠ FirstRanker.com ---

Glucose

Chemically Glucose is a Monosaccharide-
Aldo Hexose C6(H2O)6
Glucose is a chief sugar of body and blood.

--- Content provided by⁠ FirstRanker.com ---

It is a primary source of energy .
In blood the predominant form is D Glucose
Brain ,RBC's lens cells are totally dependent

on Glucose.

--- Content provided by‌ FirstRanker.com ---

Main metabolic fates of Glucose is
To completely oxidize to liberate CO2 ,H2O and

ATP.

--- Content provided by‍ FirstRanker.com ---

When Glucose is excess, it is converted to

Glycogen and Fat and stored as reservoir of

--- Content provided by⁠ FirstRanker.com ---

energy.

Blood Glucose is regulated by the hormonal

influence.

--- Content provided by‌ FirstRanker.com ---

Insulin hormone lowers the blood Glucose.
Glucagon and Epinephrine increases blood

Glucose.

--- Content provided by‌ FirstRanker.com ---

Aim Of An Experiment

Estimate the amount of

Glucose present in the given

--- Content provided by FirstRanker.com ---

test specimen

Col ection of Blood Sample

--- Content provided by⁠ FirstRanker.com ---

Intravenous blood is withdrawn
Collected in Tube containing Sodium

Fluoride(NaF) and Potassium Oxalate

--- Content provided by​ FirstRanker.com ---

(1:3 mixture)

NaF is antiglycolytic agent- Inhibits

Enolase of Glycolysis.

--- Content provided by‍ FirstRanker.com ---

Potassium Oxalate- Anticoagulant.
Specimens used for Glucose

estimation:

--- Content provided by‍ FirstRanker.com ---

?Whole blood
?Plasma
?Serum

--- Content provided by⁠ FirstRanker.com ---

Conditions Of blood Samples

Fasting Blood Sample (FBS):

qBlood sample collected in fasting condition after 10

--- Content provided by‍ FirstRanker.com ---

-12 hrs of fast.

Post Prandial Blood Sample (PP Sugar):

--- Content provided by FirstRanker.com ---

vBlood sample collected after 2 hrs of meals.

Random Blood Sample (RBS):

? Blood sample collected any time.

--- Content provided by‍ FirstRanker.com ---

Methods Used

True Glucose Method-Based on

Enzyme Use.

--- Content provided by‍ FirstRanker.com ---

? GOD-POD Method
? Hexokinase

Based on Reducing Property Of Sugar.

--- Content provided by​ FirstRanker.com ---

vFolin Wu Method
vOrtho Toluidine Method

Principle Based On Reducing

--- Content provided by⁠ FirstRanker.com ---

Property

In hot and alkaline medium Glucose is

--- Content provided by FirstRanker.com ---

transformed to Enediol which reduces

the cupric ions to cuprous ions and

form the precipitate of Cuprous oxide.

--- Content provided by‌ FirstRanker.com ---

Cuprous oxide then reduces

Phosphomolybdate to Molybdenum

--- Content provided by FirstRanker.com ---

blue.
The intensity of blue color

produced is directly

--- Content provided by⁠ FirstRanker.com ---

proportional to the amount of

reduction reaction brought by

reducing sugar.

--- Content provided by​ FirstRanker.com ---

The Optical Density of colored

solution is measured

--- Content provided by FirstRanker.com ---

calorimetrically.

A Glucose standard of 100

mg% is run similarly for

--- Content provided by‌ FirstRanker.com ---

comparison and calculation of

unknown concentration of

--- Content provided by⁠ FirstRanker.com ---

Glucose present in test

specimen.
Methods based on reducing property of

--- Content provided by​ FirstRanker.com ---

sugar are not true glucose methods.

Actual Glucose concentration of blood

specimen cant be estimated out by

--- Content provided by‍ FirstRanker.com ---

these methods.

In these methods other reducing

--- Content provided by‌ FirstRanker.com ---

substances present in blood samples

also reduce and give the reaction.

Result values are higher than actual

--- Content provided by‍ FirstRanker.com ---

Glucose concentration.

Principle Of GOD-POD Method
Glucose present in a test specimen is

--- Content provided by​ FirstRanker.com ---

acted upon by an enzyme Glucose

Oxidase (GOD) which oxidizes Glucose

--- Content provided by FirstRanker.com ---

to Gluconic acid and H2O2.

The enzyme Peroxidase (POD) then act

on H2O2 to liberate water and nascent

--- Content provided by​ FirstRanker.com ---

oxygen.

Nascent oxygen then reacts with a

--- Content provided by‍ FirstRanker.com ---

chromogen 4-Aminoantipyrine to form

a pink color complex.

True Glucose Methods

--- Content provided by‍ FirstRanker.com ---

The enzymatic based methods

for Glucose estimation are true

--- Content provided by​ FirstRanker.com ---

Glucose methods.

The enzyme specifically act on

Glucose and measure the

--- Content provided by FirstRanker.com ---

amount more accurately.
Protocol

S. No

--- Content provided by FirstRanker.com ---

Test

Standard

--- Content provided by‍ FirstRanker.com ---

Blank

Distilled

1.8 ml

--- Content provided by‍ FirstRanker.com ---

1.8 ml

2 ml

--- Content provided by‌ FirstRanker.com ---

water

Plasma

0.2 ml

--- Content provided by⁠ FirstRanker.com ---

-------

--------

--- Content provided by​ FirstRanker.com ---

Glucose

-------

0.2 ml

--- Content provided by‌ FirstRanker.com ---

--------

Standard

--- Content provided by⁠ FirstRanker.com ---

Glucose

3 ml

3 ml

--- Content provided by⁠ FirstRanker.com ---

3 ml

Reagent

--- Content provided by FirstRanker.com ---

Mix all the contents of the tube .
Incubate the tubes at 37 degree

centigrade for 15 minutes.

--- Content provided by‍ FirstRanker.com ---

Read the O.D readings by

adjusting the filter to green (520

nm).

--- Content provided by⁠ FirstRanker.com ---

Record the O.D readings of Test,

Standard and Blank.
Calculation

--- Content provided by​ FirstRanker.com ---

Blood Glucose in mg% = O.D of T x 100

O.D of S

--- Content provided by​ FirstRanker.com ---

Results

The blood Glucose of

given test sample =

--- Content provided by‍ FirstRanker.com ---

mg%
Clinical Interpretation

Normal Ranges

--- Content provided by⁠ FirstRanker.com ---

Fasting Blood Glucose= 70-110 mg%
Post Prandial Glucose = 110-140 mg%
Random Glucose = 80-140 mg %

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Conditions Of Hyperglycemia

When estimated blood Glucose is above

the normal range it is hyperglycemia.

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vDiabetes mellitus (Common Condition )

vStress, Anxiety , Anger , Fear
vHyper Thyroidism

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vHyper Pituitarism
vHyper Adrenalism

Conditions Of Hypoglycemia

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When the estimated blood Glucose is below

the normal range it is hypoglycemia.

qInsulin Over dose

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qPancreatic Tumors (Insulinomas)
qProlonged Starvation
qHypo Adrenalism
qHypo Pituitarism
qHypo Thyroidism

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Rol No's- Even No's

Observations
O.D of Test= 0.30
O.D of Standard= 0.28

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Calculate Blood Glucose in mg%
Interpret your results.


Rol No's- Odd No's

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Observations
O.D of Test= 0.60
O.D of Standard= 0.28
Calculate Blood Glucose in mg%

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Interpret your results.



Thank You

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