carbamoyl-phosphate synthase

Carglumic Acid (Ureidoglutaric acid) is an orphan drug used to treat hyperammonemia in patients with N-acetyl glutamate synthase absence. This rare hereditary disease results in elevated blood levels of ammonia, which can eventually cross the blood-brain barrier and lead to neurologic problems, coma, cerebral edema, and death. Carglumic acid was approved by the U.S. FDA on 18 March 2010.

N-Acetyl-L-glutamic acid (Ac-L-Glu-OH) (NAcGlu) is an acetylated amino acid. NAcGlu is biosynthesized from glutamic acid and acetyl-CoA by the enzyme N-acetyl glutamate synthase (NAGS). NAcGlu activates carbamoyl phosphate synthetase in the urea cycle. A deficiency in N-acetyl glutamate synthase or a genetic mutation in the gene coding for the enzyme will lead to urea cycle failure in which ammonia is not converted to urea, but rather accumulated in the blood leading to the condition called Type I hyperammonemia.

H3B-120 is a highly selective, competitive, and allosteric carbamoyl phosphate synthetase 1 (CPS1) inhibitor with an IC50 of 1.5 μM and a Ki of 1.4 μM, exhibiting anti-cancer activity.