N-Acetylglutamic acid

N-Acetylglutamic acid (also referred to as N-acetylglutamate, abbreviated NAG, chemical formula C7H11NO5) is biosynthesized from glutamate and acetylornithine by ornithine acetyltransferase, and from glutamic acid and acetyl-CoA by the enzyme N-acetylglutamate synthase. The reverse reaction, hydrolysis of the acetyl group, is catalyzed by a specific hydrolase. It is the first intermediate involved in the biosynthesis of arginine in prokaryotes and simple eukaryotes and a regulator in the process known as the urea cycle that converts toxic ammonia to urea for excretion from the body in vertebrates. N-Acetylglutamic acid (also referred to as N-acetylglutamate, abbreviated NAG, chemical formula C7H11NO5) is biosynthesized from glutamate and acetylornithine by ornithine acetyltransferase, and from glutamic acid and acetyl-CoA by the enzyme N-acetylglutamate synthase. The reverse reaction, hydrolysis of the acetyl group, is catalyzed by a specific hydrolase. It is the first intermediate involved in the biosynthesis of arginine in prokaryotes and simple eukaryotes and a regulator in the process known as the urea cycle that converts toxic ammonia to urea for excretion from the body in vertebrates. N-Acetylglutamic acid is an extracellular metabolite isolated from the prokaryote Rhizobium trifolii that was characterized using many structure determination techniques such as proton nuclear magnetic resonance (1H NMR) spectroscopy, Fourier-transform infrared spectroscopy, and gas chromatography-mass spectrometry. In Rhizobium, extracellular build-up of N-acetylglutamic acid is due to metabolism involving nod factor genes on a symbiotic plasmid. When the nod factors are mutated, less N-acetylglutamic acid is produced. In prokaryotes and simple eukaryotes, N-acetylglutamic acid can be produced by N-acetylglutamate synthase (NAGS) or ornithine acetyltransferase (OAT). OAT synthesizes N-acetylglutamic acid from glutamate and acetylornithine and is the method of choice for production in prokaryotes that have the ability to synthesize the compound ornithine. N-Acetylglutamate synthase is an enzyme that serves as a replenisher of N-acetylglutamic acid to supplement any N-acetylglutamic acid lost by the cell through mitosis or degradation. NAGS synthesizes N-acetylglutamic acid by catalyzing the addition of an acetyl group from acetyl-coenzyme A to glutamate. In prokaryotes with non-cyclic ornithine production, NAGS is the sole method of N-acetylglutamic acid synthesis and is inhibited by arginine. Acetylation of glutamate is thought to prevent glutamate from being used by proline biosynthesis. Vertebrates do not have OAT therefore N-acetylglutamic acid is exclusively synthesized by NAGS in liver mitochondria. In contrast to prokaryotes, NAGS in mammals is enhanced by arginine, along with protamines. It is inhibited by N-acetylglutamic acid and its analogues (other N-acetylated compounds). The brain also contains N-acetylglutamic acid at trace amounts, however no expression of NAGS is found. This suggests that N-acetylglutamic acid is produced by another enzyme in the brain that is yet to be determined. In vertebrae and mammals, N-acetylglutamic acid is the allosteric activator molecule to mitochondrial carbamyl phosphate synthetase I (CPSI) which is the first enzyme in the urea cycle. It triggers the production of the first urea cycle intermediate, carbamyl phosphate. CPSI is inactive when N-acetylglutamic acid is not present. In the liver and small intestines, N-acetylglutamic acid-dependent CPSI produces citrulline, the second intermediate in the urea cycle. Liver cell distribution of N-acetylglutamic acid is highest in the mitochondria at 56% of total N-acetylglutamic acid availability, 24% in the nucleus, and the remaining 20% in the cytosol. Aminoacylase I in liver and kidney cells degrades N-acetylglutamic acid to glutamate and acetate. In contrast, N-acetylglutamic acid is not the allosteric cofactor to carbamyl phosphate synthetase found in the cytoplasm, which is involved in pyrimidine synthesis.