Biochemistry · Amino Acid Metabolism and Urea Cycle (Disorders, Phenylketonuria)

In the urea cycle, N-acetylglutamate (NAG) is the essential allosteric activator of carbamoyl phosphate synthetase I (CPS-I). NAG synthesis increases after a protein-rich meal because:

  • A Arginine activates NAG synthase, signalling high amino acid load
  • B Glutamate directly activates CPS-I without NAG as intermediary
  • C Ornithine inhibits NAG synthase feedback
  • D Citrulline allosterically activates CPS-I
Correct answer: A. Arginine activates NAG synthase, signalling high amino acid load

Explanation

N-acetylglutamate is synthesised from glutamate + acetyl-CoA by NAG synthase, which is allosterically activated by arginine. After a protein-rich meal, arginine availability rises, stimulating NAG synthesis and thereby activating CPS-I — the rate-limiting enzyme of the urea cycle. This elegant feed-forward mechanism couples dietary protein load to urea cycle capacity. NAG deficiency (NAG synthase deficiency) presents with hyperammonemia and responds dramatically to N-carbamylglutamate (a stable NAG analogue) treatment.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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