Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 51 Integrated Metabolism Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.
Integrated Metabolism
OR
Intermediary Metabolism
OR
Interrelationship Between
Various Metabolic Pathways
OR
Interdependence Of Metabolic
Pathways
To Better Understand Metabolism Of
Various Biomolecules
? Metabolism of each chief
biochemical was studied
individual y and separately.
? This was just for convenience
and better understanding of
? Various metabolic pathways
associated with each
biochemical constituent.
What is Integrated Metabolism?
? Various metabolic reactions, pathways and
processes of important biochemical moieties of
human body viz:
? Carbohydrates
? Lipids
? Proteins
? Nucleic acids
? Hemoglobin
? Takes place in different cells and cellular
compartments of specific tissues and organs.
? For maintaining normal health ,growth and
reproduction.
The Metabolic Pathways Of Cel s
Takes Place
? Synergistical y
? Closely Interrelated/Integrated
? With Interdependence
? In a Regulated manner
? With good coordination
? In the cellular compartments
of the body
? Various metabolic pathways
related to different metabolic
moieties
?Takes place synergistical y, as
per the cellular conditions.
Factors Regulating Metabolism
? Hormones are the 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 ATP and AMP
?Citrate levels
?Fructose 2,6 Bisphosphate levels
? Low and high levels of ATP stimulate and
inhibit the regulatory enzymes of Glycolysis
and TCA.
? Increased levels of 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.
Evidences Of
Metabolic Interrelationships
Interrelationships
Of
Carbohydrate with Lipid Metabolism
Free Excess Glucose In Wel Fed
Condition Is a Source For Lipogenesis
? Pyruvate end product of Glycolysis is
oxidatively decarboxylated to Acetyl-
coA
? Acetyl-coA is then utilized via TCA
cycle
? Acetyl-coA of Glucose when excess is
diverted and used for biosynthesis of
Fatty acids and Cholesterol.
? 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.
? When Carbohydrates taken in
excess can be converted 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
? The TCA cycle intermediates are
very significant
? These intermediates are
influxed and effluxed as per the
cellular need and maintain
biochemical Homeostasis.
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 used for
the biosynthesis of:
I. Glucose
I . Amino acids
I I. Fatty acids
IV. Heme
Interrelationship Of
TCA with Urea Cycle
Interrelationship Of
Lipid and Carbohydrate
Metabolism
? Fat burns under the Flame of
Carbohydrates
? For complete oxidation of Fatty
acids
? Their needs presence of
sufficient amount of cel ular
Glucose.
?In a wel fed
conditions
?The major source of
OAA is Glucose.
?Oxaloacetate is an
essential initiating
metabolite for the
TCA cycle.
?OAA serve as a flame
for oxidation of
Acetyl CoA via TCA
cycle.
? Cel ular deprivation of Glucose
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.
Interrelationship
Of
Carbohydrates
And
Protein Metabolism
? Intermediates of Carbohydrate
metabolism can be a source of
? Carbon skeleton for biosynthesis of
non Essential amino acids.
vPyruvate to Alanine
vOAA to Aspartate
vKetoglutarate to Glutamate
-oxidation of Fatty acid and it's
Interrelationship
? The 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 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.
?Fatty acids are also not
a source for Amino
acids Biosynthesis in
human body .
Interrelationship With ETC
? Reduced coenzyme NADH+H+
generated in Glycolysis
? By action of Glyceraldehyde? 3 ?
Phosphate Dehydrogenase
? Enter in ETC for its reoxidation
and ATP generation.
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
? The Ribose-5-phosphate
(pentose sugar) of HMP
shunt is integrated for
?Biosynthesis of Purine &
Pyrimidine Nucleotides.
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.
Interrelationships of
Uronic acid pathway
? Glucuronic acid of Uronic acid
pathway is integrated with Phase
I conjugation reactions of
detoxification process.
?Glucuronic acid is involved in
Bilirubin and other drug
metabolism.
?Glucuronic acid is involved
in Mucopolysaccharide
biosynthesis.
? 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
v Important Metabolites in human
body who function as crossroads of
metabolism :
1. Pyruvate
2. Acetyl-CoA
3. OAA
4. Succinyl-CoA
Formation And Fates
Of
Pyruvate
Formation And Fates
Of
Acetyl CoA
Formation And Fates Of Oxaloacetate
OR
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
75
Liver
? Biochemical Factory of Human body
? Metabolical y very active in all
states (well fed and fasting).
? Has good coordination with other
body organs.
? Liver is a Glucostatic organ regulates
blood Glucose in al conditions.
?In a wel fed condition Liver
stores excess free Glucose as
Glycogen.
?In emergency condition In Liver
Glycogen is degraded via
Glycogenolysis and
biosynthesizes Glucose via
Gluconeogenesis.
?Liver biosynthesizes
endogenous Lipids and
mobilize out it as VLDL
for extra hepatic use.
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
83
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 for its activity.
? 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
? During Starvation -> Important site of
Gluconeogenesis (1/2 of blood Glucose)
91
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 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
metabolite.
? 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 the levels of intermediary
metabolites and maintain their
equilibrium.
4. To coordinate with the 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
? Doctors are responsible for confirm diagnosis and
treatment of 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 the related
complexities.
? Rule out the right biochemical underlying cause
of metabolic disorders and pathogenesis.
? Try correct the altered metabolism in treatment.
? Prerequisite to Become A Good
Doctor Is to
?Acquire Profound Knowledge of
Integrated Metabolism
?With Good Concepts And its
Understanding.
A good Doctor is one
Who has An
Understanding Knowledge
of Biochemistry
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
Biochemistry Department
This post was last modified on 05 April 2022