L22: Amino Acid Catabolism

Question 1

LO1: Describe the two major types of reactions for removing amino groups from amino acids

Answer 1

To remove amino groups from amino acids:

1. deamination to produce free ammonia
2. transamination to transfer AA groups to a common acceptor (usually alpha-ketoglutarate)

Question 2

LO2: Explain the basis for classifying amino acids as glucogenic or ketogenic

Answer 2

GLUCOGENIC: have carbon skeletons that can be converted into substrates for glucose synthesis (pyruvate, oxaloacetate, alpha-ketoglutarate, succinyl-CoA or fumarate)

KETOGENIC: degraded to acetyl-CoA or acetoacetyl-CoA to be used for synthesis of ketones and FAs

Question 3

LO3: Name the glucogenic AAs, the ketogenic AAs, and the AAs that are both

Answer 3

GLUCOGENIC COMPOUNDS: alanine, aspartate, and glutamate are VIP; also included are serine, cysteine, glycine, threonine, tryptophan, asparagine, methionine, threonine, isoleucine, valine, glutamine, proline, arginine, histidine, phenylalanine

KETOGENIC COMPOUNDS: leucine and lysine

BOTH: isoleucine, phenylalanine, tyrosine, tryptophan

Question 4

LO4/LO5: Identify two major reactions that prevent accumulation of ammonia from AA metabolism in peripheral tissues

Answer 4

1. Transamination reactions: transaminases specific for certain AA nitrogen donors transfer amino nitrogen from donor to an alpha-ketoacid acceptor
   - VIP transaminases= ALT and AST
   - VIP acceptors= alpha-ketoglutarate, OAA, pyruvate
2. Glutamine synthetase reaction: catalyzes condensation of ammonia with glutamate to glutamine; glutamine=non-toxic interorgan ammonia carrier

Question 5

LO5: Name the three principal alpha-keto acids that serve as acceptors of amino groups, and discuss the role that each plays in AA metabolism

Answer 5

alpha-ketoglutarate: major acceptor of amino group for most transaminases (first step in flow of amino nitrogen); transfer generates gluatmate and alpha-keto acids

OAA: accepts amino group from liver AST to form aspartate, a direct N donor in urea synthesis

pyruvate: receives N from glutamate via muscle ALT to generate alpha-ketoglutarate and alanine (non-toxic form of N for transport in blood to the liver)

Question 6

LO6: Identify the role of Vit B6 in AA metabolism

Answer 6

Vit B6 (pyridoxine and pyridoxal)= precursor for pyridoxal phosphate, which acts as a coenzyme for many enzymes that catalyze reactions involving transformations around alpha-carbon atoms of amino acids

Question 7

LO7: Describe the general route by which the AA nitrogen in muscle gets incorporated into glutamate or aspartate in liver

Answer 7

Transaminases transfer their amino groups to alpha-ketoglutarate to generate glutamate (and various alpha-ketoacids)
-muscle ALT transfers N from glutamate to pyruvate

Liver AST transfers N to OAA to generate aspartate, a direct N donor in urea synthesis

Question 8

LO8: Explain why patients receiving either isoniazid or penicillamine therapy may require pyridoxine supplements

Answer 8

Isoniazid=TB drug
-reacts with pyridoxal (Vit B6) and makes it unavailable for phosphorylation by pyridoxal kinase, so pyridoxal phosphate doesn’t form and transaminases (VIP), decarboxylases, deaminases, racemases and aldolases lose their function due to lack of their pyridoxal phosphate co-enzyme

Penicillamine= used to treat Wilson’s disease, a Cu+2 storage disease
-also inactivates pyridoxal (Vit B6) and has similar effects on reactions involving transformations around the alpha-carbon of AAs (particularly transaminations)