NAGS: Mitochondria 1:2,000,000 AR N-acetylglutamate
Under this agreement, Medunik Canada receives the exclusive Canadian rights to market and distribute four important therapies in the following medical conditions: (1) acute hepatic porphyria, (2) hyperammonaema due to N-acetylglutamate
synthase (NAGS) deficiency or one of three organic acidurias (isovaleric, methylmalonic or propionic), (3) patent ductus arteriosus and (4) vitamin E deficiency in chronic cholestasis.
These include carbamoyl phosphate synthetase I (CPS I) deficiency, N-acetylglutamate
synthetase (NAGS) deficiency, ornithine transcarbamylase (OTC) deficiency, argininosuccinate synthetase (ASS) deficiency (which is also known as citrullinemia), argininosuccinate lyase (ASL) deficiency and arginase 1 deficiency (hyperargininemia).
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 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.
The condition, N-acetylglutamate
synthase or NAGS deficiency, is an extremely rare, genetic disorder that can be present in babies soon after birth.