N-acetylglutamate synthase (NAGS)

N-acetylglutamate synthase (NAGS) is a mitochondrial enzyme that catalyzes the formation of N-acetylglutamate from glutamate and acetyl-CoA, primarily in the liver[2][1]. N-acetylglutamate is a crucial allosteric activator of carbamoyl phosphate synthase I, the enzyme initiating the urea cycle for effective ammonia detoxification in mammals[1][2][3][4]. In microorganisms and plants, NAGS functions as a key enzyme for arginine biosynthesis[2][3]. Deficiency of NAGS causes a rare inborn error of metabolism—N-acetylglutamate synthase deficiency—resulting in impaired urea cycle function, potentially life-threatening hyperammonemia, and neurological symptoms[1][5]. Treatment with N-carbamylglutamate, a synthetic analog of N-acetylglutamate, can restore urea cycle activity and is an approved therapy for NAGS deficiency[5].

Other names

N-acetylglutamate synthase, mitochondrialN-acetylglutamate synthase long formN-acetylglutamate synthase short formN-acetylglutamate synthase conserved domain formAGASARGANAT7Amino-acid acetyltransferaseN-acetylglutamate synthetase

Allosteric activation of carbamoyl phosphate synthase I by production of N-acetylglutamate; Restoration of urea cycle function through N-carbamylglutamate supplementation in deficiency