Carbamoyl phosphate synthetase (CPS (CPSase); specific isoforms include CPS I and CPS II)

Carbamoyl phosphate synthetase is a large, multifunctional enzyme that catalyzes the ATP-dependent synthesis of carbamoyl phosphate from bicarbonate and ammonia or glutamine.[1][2][7] There are two major isoforms in mammals: Carbamoyl phosphate synthetase I (CPS I) is located in mitochondria and is essential for the urea cycle, catalyzing the first committed step in the detoxification of ammonia by converting it to carbamoyl phosphate, with N-acetylglutamate as an essential allosteric activator.[2] Carbamoyl phosphate synthetase II (CPS II) is cytosolic and participates in de novo pyrimidine biosynthesis using glutamine as the nitrogen source. The enzyme is a heterodimer in bacteria (small and large subunits), where the small subunit hydrolyzes glutamine, providing ammonia, and the large subunit catalyzes sequential phosphorylation steps to form carbamoyl phosphate. The structure includes channeling tunnels to efficiently transfer unstable intermediates between active sites.[1][3][5][7] Hereditary deficiency of CPS I results in a rare but severe urea cycle disorder characterized by hyperammonemia.[2]

Other names

Carbamoyl phosphate synthaseCPSaseCarbamoyl phosphate synthetase I (CPS I)Carbamoyl phosphate synthetase II (CPS II)

Allosteric activation by N-acetylglutamate (for CPS I)[2]. Drugs target upstream or pathway modulation, not the enzyme directly.