Q64.Carbamoyl phosphate synthetase I (first enzyme in urea cycle) is allosterically regulated by:
(1) N-acetylglutamate
(2) N-acetylglucosamine
(3) N-acetylgalactosamine
(4) N-acetylgluconate
Carbamoyl Phosphate Synthetase I Regulation
Carbamoyl phosphate synthetase I (CPS1), the urea cycle’s first enzyme, is allosterically activated by N-acetylglutamate to respond to high ammonia levels.
Correct Answer
Option (1) N-acetylglutamate is the allosteric regulator of CPS1.
N-acetylglutamate (NAG) binds CPS1’s allosteric site, boosting activity up to 50-fold by enhancing substrate affinity and Vmax, linking regulation to arginine and glutamate availability.
Option Breakdown
CPS1 Activation Mechanism
CPS1 catalyzes NH₄⁺ + HCO₃⁻ + 2ATP → carbamoyl phosphate + 2ADP + Pi in mitochondria, but basal activity is low without NAG.
NAG binding to the L4 domain induces conformational shifts in A-loop and T’-loop, synchronizing active sites across CPS1’s trimeric structure.
This ensures urea cycle activation only during hyperammonemia, preventing wasteful carbamoyl phosphate diversion to pyrimidines.
The diagram illustrates CPS1 in metabolic context, highlighting its regulated entry into the urea cycle.
