Carbamoyl-phosphate synthase 1 (CPS1)

Carbamoyl-phosphate synthase 1 (CPS1) is a mitochondrial enzyme that catalyzes the first and rate-limiting step of the urea cycle, enabling detoxification of ammonia in the liver by converting ammonia and bicarbonate to carbamoyl phosphate[1][3][5]. This reaction is essential for the safe excretion of excess nitrogen as urea. CPS1 activity is dependent on the allosteric activator N-acetylglutamate, linking its activity to metabolic signals indicating nitrogen overload[1][5]. Genetic deficiency of CPS1 leads to hyperammonemia, with severe neurological consequences if untreated[3][6]. The enzyme belongs to the ligase (EC 6.3.4.16) family and is encoded by the CPS1 gene. It is not a receptor, but an essential metabolic enzyme in nitrogen disposal, targeted therapeutically by providing activators (e.g., carglumic acid) in deficiency states[6]. There are no common pharmacological inhibitors or drugs used to block CPS1, as the disease risk stems from reduced or lost function rather than excess activity.

Other names

CPS ICPSICarbamoyl phosphate synthetase IAmmonia ligase (mitochondrial)

Enzyme activation (by N-acetylglutamate, allosteric modulation) Substitution therapy (with Carglumic acid, which mimics N-acetylglutamate to activate CPS1 in deficiency)