Download MBBS Biochemistry PPT 63 Integrated Metabolism Lecture Notes

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Induction To Todays Topic

WORLD OF HUMAN BEINGS


HUMAN INTER-RELATIONSHIPS


WORLD OF BIOMOLECULES

And

INTER-RELATIONSHIPS



ANY GUESSES FOR TODAYS TOPIC ?
Integrated Metabolism

OR

Intermediary Metabolism

OR

Interrelationship Between

Various Metabolic Pathways

OR

Interdependence Of Metabolic

Pathways

What Is an Essence of

Normal, Health, Growth and Reproduction

of Human Body?
Normal Metabolism of Biomolecules

Metabolism and Types



Important Factors Of Metabolism

?Metabolites
?Hormones
?Enzymes
?Cofactors
?Coenzymes
?Water
?Oxygen

? Various metabolic reactions, pathways and

processes of important biomolecules of human

body viz:

? Carbohydrates
? Lipids
? Proteins
? Nucleic acids
? Hemoglobin

? Taking place in different cells and cellular

compartments of specific tissues and organs.


Significance To Study

Individual Metabolic Pathways

Of Various Biomolecules


? Metabolism of each chief

biomolecule was studied

individual y and separately.

? For convenience and clear

understandings of metabolic

reactions associated to it.


Features of

Normal Metabolic Pathways
1. Well Planned
2. Compartmentalized
3. Well Organized/ More Systematic
4. Require Specific Conditions
5. Synergistic/Simultaneous
6. Flexible/Adapt/Change for good survival
7. Induced as per condition
8. Regular in its operation
9. Regulated/Control ed/Balanced
10. Good cooperation and coordination

Hormones Regulate Metabolism
? Hormones are key regulators of

Enzymes

? Regulatory Enzymes are stimulated or

inhibited by specific hormones

? Enzymes are regulated by:

?Al osteric Regulation
?Covalent Modifications

Metabolism Is Regulated By

? Availability of Substrates Regulate

Metabolism :

?Ratio of Insulin/Glucagon
?Ratio of ATP and AMP
?NADH/NAD
?Citrate levels
?Fructose 2,6 Bisphosphate levels
? Low and high levels of ATP stimulate and

inhibit regulatory enzymes of Glycolysis and

TCA.

? Increased levels of Acetyl-CoA and Citrate

stimulates enzyme Acetyl CoA Carboxylase

of De Novo biosynthesis of Fatty acid.

? Increased Fructose 1,6 Bisphosphatase is

? Al osteric stimulator of PFK of Glycolysis
? Al osteric inhibitor of Fru1,6Bis Phosphatase

of Gluconeogenesis.

What is an Integrated Metabolism?
? Metabolic pathways are Closely

Interrelated/Integrated

/Interdependent

?Not total y dependent nor total y

independent

OR

?But partial dependence and partial

independence

Stages Of Integrated Metabolism




Evidences Of

Metabolic Interrelationships

Interrelationships

Of

Carbohydrates with Lipid Metabolism


Free Excess of Glucose

In Wel Fed Condition

Is a Source For Lipogenesis
Acetyl-CoA Obtained from

Glucose Metabolism

Is Precursor for

Lipid Metabolism

(Fatty acids and Cholesterol)

? Pyruvate (3C Keto acid) an end product

of Glycolysis is oxidatively

decarboxylated to Acetyl-CoA

? Acetyl-CoA is then utilized via TCA

cycle

? Acetyl-CoA obtained from Glucose

when excess is diverted and used for

biosynthesis of Fatty acids and

Cholesterol.
Glyceraldehyde Of Glycolysis

Integrated as Glycerol

of

TAG and Glycerophospholipid

? Glyceraldehyde-3-phosphate an

intermediate of Glycolysis of Glucose ,

is a source for Glycerol production.

? Glycerol obtained from Glucose is

utilized during Lipogenesis ,for

biosynthesis of Triacylglycerol and

Phospholipid biosynthesis.


? Thus when Carbohydrates

ingested in excess can be

transformed to TAG which is


? Stored as reserve source of

energy in Adiposecytes

Interrelationships

Of

TCA Cycle
TCA Cycle

Is an

Excellent Example

of

Integrated Metabolism

? TCA cycle intermediates are very

significant

? These intermediates are influxed

and effluxed as per the cel ular

need and maintain biochemical

Homeostasis. (Anaplerotic

Reactions)


Efflux of TCA Intermediates

? Citrate ? Denovo Biosynthesis of Fatty

acids.

? OAA is reversibly transaminated to

Aspartate.

? Ketoglutarate reversibly transaminated

to Glutamate.

? Succinyl CoA is effluxed for Heme

biosynthesis and Ketolysis.
Influx of TCA Cycle Intermediates

? Ketoglutarate is added by Glutamate by it's

Glutamate Dehydrogenase activity.

? Succinyl -CoA is obtained from Propionyl-CoA

which is a source from B-oxidation of odd chain

fatty acid

? Catabolism of Valine, Isoleucine & Methionine

(VIM) amino acids forms Succinyl-CoA.

? Fumarate is influxed through

Phenylalanine & Tyrosine

metabolism

? Fumarate also through Urea

cycle by Argininosuccinase

activity.




Points To Remember

? TCA intermediates are involved

for biosynthesis of:

I. Glucose

I . Amino acids

I I. Fatty acids And Cholesterol

IV. Heme


Interrelationship Of

TCA with Urea Cycle



Interrelationships Of

Lipid With Carbohydrate

Metabolism
Fat Burns Under Flame of

Carbohydrates

? Fat burns under the Flame of

Carbohydrates

? For complete oxidation of Fatty

acids

? Their needs presence of

sufficient amount of cel ular

Glucose.


Oxaloacetate Serves Flame for Complete

Oxidation Of Fatty acid

? In a well fed condition
? Major source for OAA is

Glucose

? By Pyruvate Carboxylase

activity
?Oxaloacetate is an

essential initiating

metabolite for TCA cycle

?Oxaloacetate (OAA)

serve as a flame for

oxidation of Acetyl

CoA via TCA cycle.
? Cel ular deprivation of Glucose

lowers OAA leads to incomplete

oxidation of Fatty acids.

? Accumulates Acetyl-CoA in

Mitochondrial matrix.

? Impermeable Acetyl-CoA is then

transformed to permeable ketone

bodies via ketogenesis.

-oxidation of Fatty acid and it's

Interrelationship
? Reduced coenzymes FADH2 &

NADH+H+ generated during it's

pathway are

? Integrated with ETC /oxidative

phosphorylation to generate

ATP.

?Acetyl-CoA formed as an end

product of oxidation of

fatty acids

?Is integrated with TCA cycle

for it's complete oxidation.
? Acetyl-coA can be a source for

Ketone bodies production via

Ketogenesis.

? To smal extent in normal

metabolic conditions and excess

in emergency conditions.

Remember

Fatty acids

cannot be converted

to Glucose In Human

Body
? Acetyl-CoA obtained from Beta-

oxidation of fatty acids cannot be

reversibly converted to Pyruvate

? Since PDH complex is irreversible in

action.

? Thus there is no net conversion of

Fatty acids (Fat) to Glucose

(Carbohydrates).

? However Propionyl-CoA an end

product of oxidation of odd chain

fatty acid

? Serve as a source for Glucose

production after conversion into

Succinyl-CoA (intermediate of TCA

cycle)

? Succinyl-CoA in turn can be a source

for Heme synthesis and Ketolysis.
Interrelationship

Of

Carbohydrates

And

Protein Metabolism

? Intermediates of Glucose

metabolism can be a source of

? Carbon skeleton for biosynthesis of

non Essential amino acids.

vPyruvate to Alanine
vOAA to Aspartate
vKetoglutarate to Glutamate


Amino Acids And Its Interrelationships
Amino acids are interrelated

for

Purine and Pyrimidine

biosynthesis

?Gly , Asp, Gln for Purine Biosynthesis
?Asp and Gln for Pyrimidine Synthesis
Amino acids are Source

For Glucose In Human Body

? Glucogenic amino acids are source

for production of Glucose via

Gluconeogenesis.

? 100 gm of Proteins can produce

approx 60 gm of Glucose in human

body.
?Amino acid Glycine is

connected to Heme

biosynthesis.

? Glycerol released during

lipolysis of TAG is integrated

? With Gluconeogenesis to

produce Glucose.


HMP Shunt and It's lnterrelationships


? Glucose is alternatively oxidized

through HMP shunt to generate:

? NADPH+H+ (reducing equivalents)

? Ribose-5- phosphate


? NADPH+H+ are integrated to:
*Biosynthesis of Fatty acids
*Biosynthesis of Cholesterol
*Drug metabolism
? Ribose-5-phosphate

(pentose sugar) of HMP

shunt is integrated for

?Biosynthesis of Purine &

Pyrimidine Nucleotides.

Interrelationships of

Uronic acid pathway


?Glucuronic acid is involved

in Mucopolysaccharide

biosynthesis.
? Glucuronic acid of Uronic acid

pathway is integrated with Phase

I conjugation reactions of

detoxification process.

?Glucuronic acid is involved in:
?Bilirubin metabolism
?Drug metabolism

Interrelationship Of ETC

? Reduced coenzyme NADH+H+

generated in Glycolysis

? By action of Glyceraldehyde? 3 ?

Phosphate Dehydrogenase

? Enter in ETC for its reoxidation

and ATP generation.

ATP and Its Interrelationships

? ATP produced during oxidative

phosphorylation are connected to:

I. Nerve impulse conduction
I . Muscular activity
I I. Active transport mechanism
IV. Biosynthetic Reactions
V. Activation Reactions

Crossroads Of Metabolism

OR

Metabolites of Cross Roads


v Four Important Metabolites in

human body who function as

crossroads of metabolism :

1. Glucose-6-Phosphate
2. Pyruvate
3. Acetyl-CoA
4. Oxaloacetate (OAA)
5. Succinyl-CoA


Formation And Fates

Of

Pyruvate

Formation And Fates

Of

Acetyl CoA



Formation And Fates Of Oxaloacetate

And

Formation And Fates Of Succinyl-CoA
Metabolites Forming

Non essential Amino acids

In Human Body

Phosphoenolpyruvate

Phenylalanine Tyrosine Tryptophan

Tyrosine

Ribose 5-phosphate

Histidine
Pyruvate

Alanine Valine Leucine

a-Ketoglutarate

Glutamate

Glutamine Proline Arginine
3-Phosphoglycerate

Serine

Glycine

Cysteine

Oxaloacetate

Aspartate

Asparagine Methionine Threonine Lysine

Isoleucine
Metabolic Profile

And

Interrelationship Among Organs

Important Metabolic Organs

And Their

Interrelationships


Metabolic Profile of Organs

121

Liver

? Biochemical Factory of Human body

? Metabolical y very active in all states

(well fed and fasting)

? Most Cooperative and Coordinated

organ/Understands responsibility and

does its work (Dutiful/Pious Organ)


Liver is a Glucostatic Organ

Regulates Blood Glucose

in al conditions


The wel -fed state:

Insulin stimulates glucose consumption and

Stimulated by an

storage in muscle and liver.

increase in blood

glucose level.

Stored as glycogen

or triacyglycerol.



?In a wel fed condition Liver stores

excess free Glucose as Glycogen

(Glycogenesis)

?In emergency condition In Liver

Glycogen is degraded via

Glycogenolysis and biosynthesizes

Glucose via Gluconeogenesis.
?Liver biosynthesizes

endogenous Lipids and

mobilizes out it as VLDL

for extra hepatic use.

?Liver Centre of Ammonia

Detoxification

Muscles

? In a normal metabolic state

muscle uses Glucose and Fatty

acids as main sources of energy.

? In a well fed state muscles has

large stores of Glycogen (3/4th)
? In contracting muscles during severe

exercise in anaerobic condition

Glycolysis ends as Lactate.

? Later Lactate is metabolized by

converting it into Glucose after carried

through blood in Liver via

Gluconeogenesis (Cori cycle).

?In resting Muscle fatty

acids are the major source

of energy

?This use spare Glucose to

be used by Brain and

Erythrocytes.


Metabolic cooperation between

the skeletal muscle and liver.

The Cori Cycle

Metabolic Profile of Muscles

136


Adipose Tissue

? TAG can be abundantly and

unlimitedly stored in adipocytes

? TAG serve as a reserve store of

energy during well fed condition.

? TAG is the major fuel for this

tissue.
Metabolic Profile of Adipose Tissue

? Needs Glucose for biosynthesis of TAG

? Glucose level determines to release

Fatty acids into blood

? Hormone sensitive Lipase is activated

when Insulin/Glucagon ratio is low

Brain

? Glucose is the main fuel of Brain

(120 gm/day)

? Fatty acids cannot be utilized by

brain as they are bound to Albumin

and cannot cross blood brain

barrier.


Metabolic Profile of Brain

60-70 % of bodies utilization of Glucose is

by Brain.

In starvation -> Ketone bodies can

replace Glucose


Brain is a major

Glucose consumer

Fatty acids do not serve as a fuel!

Consumes about 120 g

glucose daily.

Erythrocytes

? Erythrocytes uses obligatorily Glucose as

a source of energy for its activity.

? Erythrocytes cannot use Fatty acids and

Ketone bodies as source of energy.

? It lacks Mitochondria hence the

Glycolysis ends in Lactate.


Metabolic Profile of Kidney

? Filtration of Blood- Plasma Ultra Filtrate
? Reabsorption ,Secretion of Substances
? From Plasma Ultra filtrate -> Water , Glucose important

absorbable metabolites reabsorbed as per the threshold

values.

? Production of Urine -> Secretion of waste products
? Important role in water, electrolyte ,acid base balance.

? During Starvation -> Important site of Gluconeogenesis

(1/2 of blood Glucose)

145


In Human Body

There Prevails

Chemical Unity In Diversity










? Intermediates/End Products of one metabolic

pathway may be connected to another

metabolic pathway of same or another.

? An end product of one metabolic

pathway of Carbohydrate is connected to

another metabolic pathway of

Carbohydrate.

? Intermediate of Carbohydrate metabolic

pathway is interrelated to a metabolic

pathway of Lipid or Nucleic acid.
Integration of Fuel Metabolism

Purine

Uric acids

Glycogen

Ribose-5-P

monophosphate

PRPP

Pyrimidine

G-6-P

monophosphate

Glycine

Serine

G-3-P

Malonyl CoA

Fatty acids

b-Oxidation

PEP

Acetoacetyl CoA

Cholesterol

Acetyl CoA

Other

Pyruvate

amino

Triacylglycerols

Oxaloacetate

acids

Alanine

TCA

Aspartate

Cycle a

Other

-ketoglutarate

Urea

amino

Urea

Other

Glutamate acids

Cycle

amino

Glutamine

acids








Why Metabolic Pathways are

Integrated?

OR

What Is the Significance Of

Integrated Metabolism

To Human Body?

Integrated Metabolism Occurs To

1. To Interconvert biochemical metabolites as

per the cel ular need

2. To meet the bodies fuel demand
3. To regulate levels of intermediary

metabolites and maintain their equilibrium

4. To coordinate with various cel s, tissues

and organs for existence

5. To impart normal biochemical

environment and maintain health
?A well coordinated and

regulated integrated

metabolism of human

body

?Protects from metabolic

catastrophes.

Significance Of

Knowledge Of Integrated Metabolism

To Doctors
? Prerequisite to Become A Good

Doctor Is to:

?Acquire Profound Knowledge of

Integrated Metabolism

?With Good Understanding

Biochemical Concepts And its

Interrelationships

Doctors Responsibility

Health Professionalist

? To Heal and Relieve Pain of Patients
? To Understand Sign Symptoms
? Correlate with Biochemical basis
? Depict Biochemical Alteration
? Confirm diagnosis
? Control, treat biochemical alterations of a

disordered patients
? Study of integrated metabolism with their

interrelationships in a normal healthy conditions

helps a doctor :

? To better understand various deranged

metabolic conditions and related complexities

? Rule out right biochemical underlying cause of

metabolic disorders and pathogenesis

? Try correct an altered metabolism in treatment

Take Home Messages


Interrelationship Of Human

Biochemical System

A good Doctor is one

Who has An

Understanding Knowledge of

Intermediary Metabolism
Questions

? Long Essays.

? Q.1.Describe the common metabolic pathway.

OR

? Why TCA cycle is called as common metabolic

pathway? Explain with reactions.

? Q.2.Explain "Fat burns under the flame of

Carbohydrates".
?Which metabolic pathway

is an excellent example of

integrated metabolism?

Justify it.

? Q.3.How Carbohydrate, Lipid & Protein

metabolic pathways are integrated &

interrelated with each other. Explain

with the help of flow diagram.

? Q.4.Explain the three stages in the

intermediary metabolism of

Carbohydrate, Lipid & Protein.


?Influx & Efflux of TCA

intermediates.

?Integration of TCA with

Urea cycle.

?Formation and Fates of

? Pyruvate
?Acetyl-CoA
?Succinyl-CoA
?Oxaloacetate
?-Ketoglutarate
? Q.5.Describe the role of

fol owing organs during

wel fed condition.

?Liver
?Brain
?Muscles
?Adipose tissues

THANK YOU

Dr Anissa Atif Mirza

Biochemistry Department

AI MS Rishikesh


Important Tips For

4/4/2022

183

Three Gifts For Human Beings

On Which Health And Success Depend Upon

How Best they are Utilized

For Significant/Good Long Term Outcome

?Body- Sense
?Time
?Energy
Factors For Quality Of Health

Normal State Of Biomolecules and Metabolism

? Intentions and Actions= Behavior (Sleep Cycle)

? Nutrition (Food Cycle)

? Environment (Companionship)

Health Factors

Il Health Factors

Positive Behavior- Sensibly

Negative Behavior- Carefree

,thoughtful ,rightful care of body ,Uncontrolled, dysregulated

by Controlled ,Regulated with

activities with disobedience rigid

obedient implementation's of Do's non implementations of Do's and

of Health and Avoid Don'ts of

high implementations of Don'ts

Health
Balanced Diet- Simple and Natural Imbalanced Diet with more

Appropriate Quality and Quantity processed and refined with poor

of all essential nutrients

quality and improper quantity of

nutrients

Proper Sleep- Time 7-8 Hrs

Improper Sleep with low time in

(Early To Bed and Early To Rise)

night and more time in day

Environment- Natural Unpolluted Environment ?

Companionship with ?

Polluted with physical, chemical

Good ,Positive, Helpers

and biological pollutants

Companions with ?

Bad,Negative,Distractors
Biomolecules And Their Processes Responsible For Health

Similar Features Implemented In Practical Human Life wil

impart Success

1. Focused and Specific

2. Implement rules and regulations/orders of

metabolism (Obedient)

3. Interdependence -Communicate and

Cooperate

4. Disciplined and Dutiful-Responsible/Sensible

5. No two works at a time- For maintaining ful

Concentration

6. Complete one priority work and start Next

priority -

7. Not much multitasking/Very few multitasking as per

need

8. Do Not get overloaded at one time

9. Understand situation and work accordingly (Adapt as

per condition)

10. Sparing actions, Distribute (Charity, Share and Care)

11. Work with good pace in regularity

12. Proof Read -No Chance of Mistakes/Less errors

13. Defined and Refined- Limitations

14. Homeostasize to be in limit and do not cross limits

15. Productive/Significant-Non Futile (Economical

,Reutilizes ,No wastage)
Tips To Ensure Good ,Healthy Life

? Live Life

? Thoughtful y,Righteously,Carefuly,Actively,Alertly

? Eat Balanced

? Proportionate Quantity and Appropriate Quality

? Drink and Breathe

? Unpol uted Water and Air

? Cultivate Cheerfulness

? Love,Share,Care,

? Thankfulness,Politeness,Selflessness

? Avoid Synthetic, Chemical Interactions

? Chemical, Inhibitions leads to Disorders

4/4/2022

189

Live a Thoughtful, Rightful and Lawful

Life

? Life is Journey of Realization

? Life is path to bring changes by corrections and

improvements

? Use Sense , Time and Energy for good significant

long-term outcome

? Adopt Do's of Health and Success

? Quit/Sacrifice don'ts with steadfastness for

prevention of Il -health and Failures
Let Al of Us Realize and Clearly Differentiate

? Do's and Don'ts of every human action
? Obedience and Disobedience
? Respect and Disrespect
? Truth and False
? Mistakes and Corrections
? Success and Failure
? Good and Bad
? Wrong and Right

? Healthy and Unhealthy
? Hygienic and Unhygienic
? Significant and Insignificant
? Helpful and Harmful
? Friend and Enemy
? Well wisher and Bad Wisher
? Patience and Impatience
? Gratitude and Thankless
? Blessings and Cursing's
Factors For Success

? Blessings

1. Selflessness/No Selfishness
2. Taking care equal y for oneself and

others

3. Obedience for truth and significant acts
4. Responsible and Dutiful
5. Being Truth and Transparent
6. Not making people wait /Lying

6. Not Cheating for our own benefits
7. Keeping and Fulfil ing Promises
8. Sharing of al good you have
9. Caring for one who needs
10. Spreading/Not Hiding significant

/true Knowledge

11. Not Distracting persons who are on

righteous path

12. Not Irritating one who is righteous
13. Lifting people who needs

14. Guiding for Right acts

15. Stopping from wrong acts

16. Not Hurting any soul with

disrespect and disobedience

17. Obeying and implementing true

words

18. Using best Sense, Energy and

Time for best long term outcome

S.No

8 Rs To Implement

1

Realize

2

Recapitulate

3

Reasoning

4

Reassess

5

Respond

6

Rehearse

7

Regular and Routine

8 4/4/2022

Rejuvenate

196




9 Ps Implement

9 Cs Implement

Prayers

Concentrate

Priorities

Communicate

Plan - Protocol

Cooperate

Practice

Commitment

Proof Read

Control

Perseverance

Coordinate

Positivity

Compensate

Patience

Companionship

Perfectionist

Cope up & Change

Best For Human Health

Thoughtfulness and Righteousness

Eating And Living Style

Natural-Planned ,Organized ,Regular , Disciplined

Simple , Humble, Care and Share

Yes for Good Stead Fast No For Bad

4/4/2022

198
Implement

Thoughtfulness and Righteousness

? Everywhere and Anywhere

? Every work and Any work

? Every time and Anytime

Tips Of Good Success

?Good Hard work
?Good Intentions
Live An Evidenced Based Life

? Acquire Knowledge- Search/Ask

(Do's and Don'ts of priority actions)

? Assess/Understand Truth

? Accept

? Apply/Implement -Truth/Dos

? Appraise/Evaluate its significance

? Spread Truth and Significance

THANKS

This post was last modified on 05 April 2022