Overview of amino acid anabolism and catabolism and fate of ammonia in amino acid metabolism. This is targeted for MBBS, MD, BDS and general Biochemistry students

1. Metabolism of Protein
Dr. V.P. Acharya

2. We Are Here
Amino acid metabolism
Urea Cycle

3. General structure of an Amino acid

4. Excess amino acids cannot be stored.
Surplus amino acids are used for fuel.
 Carbon skeleton is converted to
Acetyl– CoA
Acetoacetyl–CoA
Pyruvate
TCA cycle intermediates
 The amino group nitrogen is converted to urea and
excreted.
Glucose, fatty acids and ketone bodies can be
formed from amino acids.
4

5. Protein Degradation
Dietary proteins are a vital source of amino
acids.
Discarded cellular proteins are another source
of amino acids.
5

7. BIOSYNTHESISOF THE NUTRITIONALLY
NON-ESSENTIALAA
METABOLIC FATE OF NITROGENATOMS
OF AA
CONVERSION OF CARBON SKELETON
OF AATO AMPHIBOLIC INTERMEDIATES
INBORN ERRORS OF METABOLISM
ASSOCIATEDWITH CATABOLIC
PATHWAY

8. Inter-organtransportofAA
 Plasma level of all AA- 1 mg/dl
 Glutamic acid- 10 mg/dl
 Fasting state:
Muscle releases Ala & Gln
Ala- taken by liver→ amino group → Urea
→ carbon skeleton → Gluconeogenesis
Glutamine- kidneys
Brain- takes up branched chain AA

9. Fed state: AA taken up by different tissues
Muscle & brain- take up branched chainAA
↓
Release Glutamine & Alanine
↓ ↓
Kidney Liver

10. CATABOLISM OF AMINO ACIDS

11. 1. Removal of α-amino group in the form of
ammonia by:
a) Transamination by Transaminases/
Aminotransferases
b) Deamination - Oxidative or Non-oxidative
 Oxidative deamination by Glutamate
dehydrogenase or AA oxidase
 Non-oxidative deamination- Amino acid
dehydratase
2. Disposal of ammonia in the form of Urea in
liver- Urea Cycle
3. Disposal of remaining carbon skeleton to CO2
and H2O by reactions of TCA cycle

12. Sources and fate of ammonia

13. 13
 1st step in catabolism of most AA
 Generally these enzyme funnel amino groups
to α– ketoglutarate.
 Usually a coupled reaction-
Transdeamination= Transamination +
Oxidative deamination
 Takes place in all cells of the body
Transamination

14.  Exchange of the alpha amino group between
one alpha AA and another alpha keto acid

15. Enzyme- Aminotransferases
Coenzyme- PLP

16. Mechanism of action of Aminotransferases

18.  PLP is linked to the ε-amino group of Lys
residue on the enzyme (Schiff base linkage)
 Schiff base- When an aldehyde gr reacts with
an amine group
 Aminotransferases act by transferring the
amino group of an amino acid to the pyridoxal
part of the coenzyme
 Pyridoxamine phosphate is generated
↓
Reacts with keto acid to form an AA & PLP
regenerated
 Example of bimolecular ping-pong reaction

19. Biological significance of Transamination
reaction
 1st step of catabolism- ammonia removed
 Synthesis of non-essential AA
 Equalization of quantities of non-essential
AA
 Help in clinical diagnosis- ALT & AST
EXCEPTION: Lys, Pro, Hyp &Thr Do not
undergo transamination;
Follow direct degradative pathway

20. Transdeamination
 Transamination followed by deamination
 Transamination- cytoplasm of all cells
 Amino gr transported to liver as Glutamate
 Glutamate- oxidatively deaminated in the
mitochondria of hepatocytes
 Physiologically both processes are linked

21. Oxidativedeamination
 Glutamate
dehydrogenase
present in liver
mitochondrial matrix
 AA are deaminated
at a rate of 50-70
g/day
 Ammonia generated
 NAD+ and NADP+ are
the coenzymes
Glutamate
dehydrogenase

22. Minorpathwaysofdeamination
1. L-AA oxidase- on all AA except hydroxyAA
and dicarboxylic AA
2. D-amino oxidase- oxidise D-AA & Gly

23. Non-oxidativedeamination
 AA dehydratase
 Ser ,Thr
 Ser dehydratase orThr dehydratase
 PLP coenzyme
 His→ Urocanic acid

24. Disposal/DetoxificationofAmmonia
1. Trapping of ammonia- trapped by
Glutamic acid → Glutamine →to liver →
Reaction reversed by Glutaminase →Urea
2. Transport of ammonia → Gln is the
transport form from brain & intestine
Alanine → transport form from muscle
Glutamate dehydrogenase- only present in
liver and hence final production of NH3
only at liver
3. Final disposal → liver → Urea cycle →
Urea → excreted through urine

26. Next………………
UREA CYCLE
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