These enzymes are carbamoyl phosphate synthetase 1 (CPS1), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), arginase and N-acetylglutamate synthetase.
Role of carglumic acid in the treatment of acute hyperammonemia due to N-acetylglutamate synthase deficiency.
Two generic medicines received a positive opinion from the CHMP: Febuxostat Mylan (febuxostat) for the prevention and treatment of hyperuricaemia and Ucedane (carglumic acid) for the treatment of hyperammonaemia due to N-acetylglutamate
synthase primary deficiency.
According to the contract, Medunik Canada will receive Canadian rights to market and distribute four important therapies in acute hepatic porphyria, hyperammonaema due to N-acetylglutamate
synthase deficiency or one of three organic acidurias, patent ductus arteriosus and vitamin E deficiency in chronic cholestasis.
The three endocrine products are carglumic acid (Carbaglu; C) for treatment of hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate
synthase (NAGS); tesamorelin (Egrifta; X) a growth hormone--releasing factor analog for reduction of excess abdominal fat in HIV-infected patients; and velaglucerase alfa (VPRIV; B) given for long-term enzyme replacement in patients with Gaucher disease.
With the aid of the allosteric activator N-acetylglutamate synthesized by NAGS, CPS1 catalyzes the transformation of ammonia to carbamoyl phosphate.
Diagnosis of N-acetylglutamate synthase deficiency by use of cultured fibroblasts and avoidance of nonsense-mediated mRNA decay.
The US Food and Drug Administration (FDA) has approved the New Drug Application (NDA) submitted by Orphan Europe for the use of Carbaglu in paediatric and adult patients for the treatment of acute hyperammonaemia due to the deficiency of the hepatic enzyme N-acetylglutamate
synthase (NAGS deficiency) and as maintenance therapy for chronic hyperammonaemia due to NAGS deficiency.
The hyperammonemia observed in methylmalonic acidemia is thought to arise because accumulated propionyl CoA interferes with formation of N-acetylglutamate, an obligatory activator of carbamyl phosphate synthase, the initial step in urea synthesis (4).
Inhibition by propionyl-coenzyme A of N-acetylglutamate synthetase in rat liver mitochondria: a possible explanation for hyperammonemia in propionic and methylmalonic acidemia.