catabolism of amino acids ketogenic glucogenic alanine pyruvate urea cycle vitamin B12 folic acid

1. Urea Cycle
Dr. Amro Yousef Al-Amleh

2. Urea Cycle
• One nitrogen of the urea molecule is supplied by free ammonia, and the
other nitrogen by aspartate.
• Glutamate is the immediate precursor of both ammonia.
• The carbon and oxygen of urea are derived from CO2.

4. • The first two reactions leading to the synthesis of urea occur in the
mitochondria, whereas the remaining cycle enzymes are located in
the cytosol.
1. Carbamoyl phosphate synthetase I (CPS-1)
2. Ornithine transcarbamoylase (OTC)
3. Argininosuccinate synthetase
4. Argininosuccinate synthetase
5. Arginase

8. Overall reaction

9. Regulation of Urea cycle

10. Fate of Urea

11. Sources of ammonia

12. Hyperammonemia
• Acquired hyperammonemia  Liver disease is common cause of
hyperammonemia
• Congenital hyperammonemia  Genetic deficiencies of each of the
five enzymes of the urea cycle.
• Ornithine transcarbamoylase deficiency, which is X-linked, is the most common
of these disorders.
• All of the other urea cycle disorders follow autosomal recessive inheritance
pattern.

13. Catabolism of Amino Acids
Breakdown of the carbon skeletons

14. Catabolism of the amino acids
1. Removal of a-amino groups
2. Breakdown of the resulting carbon skeletons
• Oxaloacetate.
• a-ketoglutarate
• Fumarate
• Succinyl CoA
• Pyruvate
• Acetyl CoA
• Acetoacetate

16. Amino acids that form oxaloacetate
1. Aspartae
2. Asparagine

17. Amino acids that form a-ketoglutarate
1. Glutamate
2. Glutamine
3. Arginine
4. Proline
5. Histidine

18. Glutamate

19. Glutamine

20. Proline

21. Arginine

22. Histidine

24. Amino acids that form pyruvate
1. Alanine
2. Cysteine
3. Serine
4. Threonine
5. Glycine
6. Tryptophan

25. Alanine

26. Cysteine

27. Serine

30. Tryptophan

31. Amino acids that form fumarate
1. Tyrosine
2. phenylalanine

34. Amino acids that form succinyl CoA
1. Methionine
2. Valine
3. Threonine
4. Isoleucine

36. Methionine

38. Fate of Homocysteine
• Homocysteine has two fates:-
1. Resynthesis of methionine: Homocysteine accepts methyl group from
N5-methyltetrahydrofolate (N5-methyl-THF) in reaction requiring
methylcobalamin, coenzyme derived from vitamin B12.
2. Synthesis of cysteine and production of succinyl CoA

41. Catabolism of the branched-chain amino acids
• The branched-chain amino acids, isoleucine, leucine, and valine, are
essential amino acids.
• They are metabolized primarily by the peripheral tissues (particularly
muscle), rather than by the liver.

42. 1. Transamination  branched-chain amino acid aminotransferase.
2. Oxidative decarboxylation branched-chain a-keto acid
dehydrogenase complex
3. Dehydrogenation FAD-linked dehydrogenation
4. End products:
• The catabolism of isoleucine  acetyl CoA and succinyl CoA, rendering it
both ketogenic and glucogenic.
• The catabolism of Valine  succinyl CoA and is glucogenic.
• The catabolism of Leucine,  acetoacetate and acetyl CoA and is ketogenic

44. Amino acids that form acetyl CoA or acetoacetyl CoA
1. Leucine is exclusively ketogenic in its catabolism, forming acetyl CoA
and acetoacetate.
2. Isoleucine  acetyl CoA + propionyl CoA.
3. Lysine: An exclusively ketogenic amino acid. Lysine is ultimately
converted to acetoacetyl CoA.
4. Tryptophan  alanine + acetoacetyl CoA.
5. Phenylalanine acetoacetate + fumarate
6. Tyrosine  acetoacetate + fumarate

45. Oxaloacetate Alpha-KGlu Pyruvate Fumarate Succinyl CoA
Acetyl CoA or acetoacetate