Urea Cycle: Regulation

NAG is an essential activator for CPS I, the rate-limiting step in the urea cycle. It increases the affinity of CPS I for ATP. NAG is synthesized from acetyl CoA and glutamate by N-acetylglutamate synthase (NAGS), as shown in Figure 1, in a reaction for which arginine is an activator. The cycle is also regulated by substrate availability (short-term regulation) and enzyme induction (long term).

Figure 1: Formation and degradation of N-acetylglutamate, an allosteric activator of carbamoyl phosphate synthetase I. CoA = coenzyme A.