InterPro domain: IPR004662

N -Acetylglutamate (NAG) fulfils distinct biological roles in lower and higher organisms. In prokaryotes, lower eukaryotes and plants it is the first intermediate in the biosynthesis of arginine, whereas in ureotelic (excreting nitrogen mostly in the form of urea) vertebrates, it is an essential allosteric cofactor for carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle. The pathway that leads from glutamate to arginine in lower organisms employs eight steps, starting with the acetylation of glutamate to form NAG. In these species, NAG can be produced by two enzymatic reactions: one catalysed by NAG synthase (NAGS) and the other by ornithine acetyltransferase (OAT). In ureotelic species, NAG is produced exclusively by NAGS. In lower organisms, NAGS is feedback-inhibited by L-arginine, whereas mammalian NAGS activity is significantly enhanced by this amino acid. The NAGS genes of bacteria, fungi and mammals are more diverse than other arginine-biosynthesis and urea-cycle genes. The evolutionary relationship between the distinctly different roles of NAG and its metabolism in lower and higher organisms remains to be determined [ 1 ].

The pathway from glutamate to arginine is:

• NAGS; N-acetylglutamate synthase ( 2.3.1.1 ) (glutamate to N-acetylglutamate)
• NAGK; N-acetylglutamate kinase ( 2.7.2.8 ) (N-acetylglutamate to N-acetylglutamate-5P)
• N-acetyl-gamma-glutamyl-phosphate reductase ( 1.2.1.38 ) (N-acetylglutamate-5P to N-acetylglumate semialdehyde)
• Acetylornithine aminotransferase ( 2.6.1.11 ) (N-acetylglumate semialdehyde to N-acetylornithine)
• Acetylornithine deacetylase ( 3.5.1.16 ) (N-acetylornithine to ornithine)
• Arginase ( 3.5.3.1 ) (ornithine to arginine)

This family includes acetylglutamate kinase and related enzymes [LysW]-aminoadipate/[LysW]-glutamate kinase (LysZ), which is involved both in the biosynthesis of lysine and arginine [ 2 ], and [LysW]-aminoadipate kinase [ 3 ].

1. N-acetylglutamate and its changing role through evolution. Biochem. J. 372, 279-90
2. Lysine and arginine biosyntheses mediated by a common carrier protein in Sulfolobus. Nat. Chem. Biol. 9, 277-83
3. Structural insight into amino group-carrier protein-mediated lysine biosynthesis: crystal structure of the LysZ·LysW complex from Thermus thermophilus. J. Biol. Chem. 290, 435-47