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INTEGRATION
OF
METABOLISM
By
N. Santhosh Kumar
Asst. Professor
Department Of Biochemistry
SIMS & RH
Tumkur
The various anabolic & catabolic pathways for
energy supply and biosynthesis of compounds are
closely coordinated - Integration of Metabolisms
All organisms possess their variable energy
demands; hence the supply is also equally variable
All Chemical transformations
fall under 6 types of enzymes
Fate of monomers
(Amino acids, Fatty acids, Glucose)
Construction of macro
molecules
Understand specific dynamic
action of foods
Supply of suitable fuel for all
tissues
Protein sparing action of CH’s
(Carbohydrates → protein)
Maintain constant blood
Glucose levels
Regulate the intermediate
metabolites
Significance of Integrated Metabolisms
Purpose
of
Metabolism
N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
ATPs
Fatty Acids
Amino Acids
Glucose
Conversion of food to energy to run cellular processes
ATP servers as the energy currency of the cells
Formation of ATPs
Muscle contraction &
active transport
Reducing power
(NADPH)
Biosynthesis of FAs
& Cholesterol
PEP to Glucose
Building blocks for
biosynthesis Ribose 5 P to NTPs
Succinyl CoA to Heme
one ‘C’unit transfers
& trans methylation
reactions
Formation of THF
& SAM
Glycerol to TG
N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
Metabolic regulations
Compartmentalization
of
Different Pathways
It allows the separation of
processes that occurs in opposite
directions, so they do not
interfere with each other
N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
Major metabolic pathways
- Glycolysis
- Glycogen metabolism
- Gluconeogenesis
- Fatty acid metabolism
- Amino acid metabolism
- Citric acid cycle
- Oxidative phosphorylation
only the liver can carry out all of the
reaction the major pathways.
Glycogen Glucose
Glycogen metabolism
Regulated Through
Covalent modification
Hormonal / Covalent modification of enzymes in
lipid metabolisms
N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
Key Junction Points between
Pathways
13
Glycogenesis
Glycolysis Gluconeogenesis
HMP
shunt
Glycogenolysis 1
2
3
4a
4b
Gly, Ala, val, Pro, Ser, Asp, Arg ,
Glu, Cys, Thr, His, Met , Gln, Asp
Glucose
Cori cycle
Acetaldehyde
Ethanol
TCA
Cycle
1
2 3
4
5
6
7
N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
Acetyl CoA
Synthesis of
Cholesterol
Acetylation reactions
(Detoxification)
Synthesis of Melatonin
Formation of Acetylcholine
Formation of
Ketone Bodies
Oxidation of TCA cycle
Denovo synthesis of FA
HMG -CoA
PYRUVATE
Acetylation of amino-
sugars ,glycoprotein
Ketogenic
a.a’s
β-Oxidation
of FA
Cytoplasmic
Synthase &
Reductase
Mitochondrial
Synthase &
lyase
N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
17
Metabolic Profile
Of
-Muscles can use glucose, fatty acids and ketone bodies
for fuel.
- muscles have stores of glycogen.
Metabolic Profile of Muscles
During vigorous exercise
90% of O2 consumed
after a period of intense muscular activity,
Heavy breathing occurs for some time
Because of more oxygen is used for oxidative phosphorylation
To restore ATPs & phosphocreatine levels
Liver requires ATP to convert lactate back into glucose
N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
SKELETAL
MUSCLE
-Creatine-Phosphate.
-Energy requirement in the skeletal muscle changes
depending on whether the muscle is resting or contracting.
-Phosphocreatine is used to rapidly regenerate ATP from
ADP using PCK
In the resting state, the major source
of fuel for the muscles is FAs.
During fasting (or) excessive activity
of muscle tissue is degraded into
amino acids & the carbon skeletons
are used for fuel.
Muscle tissues lack the enzymes to
convert ammonia into urea.
Instead ALT transfer the amino group
to pyruvate to form alanine. Deamination
s
Cardiac Muscle
Cardiac muscle is unique because, it is
constantly active, undergoes aerobic oxidation
Does not contain any stores as glycogen
or TGs
Glucose, FFAs , ketone bodies & Lactate
may also be the fuel for heart tissue
N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
23
To synthesize, Store
triacylglycerol & release
fatty acids as needed.
Adipocyte tissue
24
The Kidney
To produce urine,
which is a vehicle for excreting water soluble waste
products
Filtered Blood plasma
(Water & glucose reabsorbed)
During starvation
Kidneys becomes an important site of gluconeogenesis and
may produce up to half of the blood’s glucose
N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
Metabolic Profile
of
Liver
26
Fate of Glucose
in the Liver
Maintain
BGL
&
Uptake the
tissues
27
Fate of Amino
Acids
in the liver
28
Fate of Fatty Acids
in the Liver
29
Dreams Don’t’ work,
Unless YOU DO
N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH

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IM-01 Integrated Metabolism

  • 1. INTEGRATION OF METABOLISM By N. Santhosh Kumar Asst. Professor Department Of Biochemistry SIMS & RH Tumkur
  • 2. The various anabolic & catabolic pathways for energy supply and biosynthesis of compounds are closely coordinated - Integration of Metabolisms All organisms possess their variable energy demands; hence the supply is also equally variable
  • 3. All Chemical transformations fall under 6 types of enzymes Fate of monomers (Amino acids, Fatty acids, Glucose) Construction of macro molecules Understand specific dynamic action of foods Supply of suitable fuel for all tissues Protein sparing action of CH’s (Carbohydrates → protein) Maintain constant blood Glucose levels Regulate the intermediate metabolites Significance of Integrated Metabolisms
  • 4. Purpose of Metabolism N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
  • 5. ATPs Fatty Acids Amino Acids Glucose Conversion of food to energy to run cellular processes ATP servers as the energy currency of the cells
  • 6. Formation of ATPs Muscle contraction & active transport Reducing power (NADPH) Biosynthesis of FAs & Cholesterol PEP to Glucose Building blocks for biosynthesis Ribose 5 P to NTPs Succinyl CoA to Heme one ‘C’unit transfers & trans methylation reactions Formation of THF & SAM Glycerol to TG N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
  • 8. Compartmentalization of Different Pathways It allows the separation of processes that occurs in opposite directions, so they do not interfere with each other N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
  • 9. Major metabolic pathways - Glycolysis - Glycogen metabolism - Gluconeogenesis - Fatty acid metabolism - Amino acid metabolism - Citric acid cycle - Oxidative phosphorylation only the liver can carry out all of the reaction the major pathways.
  • 10. Glycogen Glucose Glycogen metabolism Regulated Through Covalent modification
  • 11. Hormonal / Covalent modification of enzymes in lipid metabolisms N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
  • 12. Key Junction Points between Pathways
  • 14. Gly, Ala, val, Pro, Ser, Asp, Arg , Glu, Cys, Thr, His, Met , Gln, Asp Glucose Cori cycle Acetaldehyde Ethanol TCA Cycle 1 2 3 4 5 6 7 N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
  • 15. Acetyl CoA Synthesis of Cholesterol Acetylation reactions (Detoxification) Synthesis of Melatonin Formation of Acetylcholine Formation of Ketone Bodies Oxidation of TCA cycle Denovo synthesis of FA HMG -CoA PYRUVATE Acetylation of amino- sugars ,glycoprotein Ketogenic a.a’s β-Oxidation of FA Cytoplasmic Synthase & Reductase Mitochondrial Synthase & lyase
  • 16. N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
  • 18. -Muscles can use glucose, fatty acids and ketone bodies for fuel. - muscles have stores of glycogen. Metabolic Profile of Muscles
  • 19. During vigorous exercise 90% of O2 consumed after a period of intense muscular activity, Heavy breathing occurs for some time Because of more oxygen is used for oxidative phosphorylation To restore ATPs & phosphocreatine levels Liver requires ATP to convert lactate back into glucose N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
  • 20. SKELETAL MUSCLE -Creatine-Phosphate. -Energy requirement in the skeletal muscle changes depending on whether the muscle is resting or contracting. -Phosphocreatine is used to rapidly regenerate ATP from ADP using PCK
  • 21. In the resting state, the major source of fuel for the muscles is FAs. During fasting (or) excessive activity of muscle tissue is degraded into amino acids & the carbon skeletons are used for fuel. Muscle tissues lack the enzymes to convert ammonia into urea. Instead ALT transfer the amino group to pyruvate to form alanine. Deamination
  • 22. s Cardiac Muscle Cardiac muscle is unique because, it is constantly active, undergoes aerobic oxidation Does not contain any stores as glycogen or TGs Glucose, FFAs , ketone bodies & Lactate may also be the fuel for heart tissue N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
  • 23. 23 To synthesize, Store triacylglycerol & release fatty acids as needed. Adipocyte tissue
  • 24. 24 The Kidney To produce urine, which is a vehicle for excreting water soluble waste products Filtered Blood plasma (Water & glucose reabsorbed) During starvation Kidneys becomes an important site of gluconeogenesis and may produce up to half of the blood’s glucose N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH
  • 26. 26 Fate of Glucose in the Liver Maintain BGL & Uptake the tissues
  • 28. 28 Fate of Fatty Acids in the Liver
  • 29. 29
  • 30. Dreams Don’t’ work, Unless YOU DO N. Santhosh Kumar / Asst. Professor / Biochem/ SIMS&RH