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N-acetylglutamate synthase (NAGS) is an enzyme that catalyses the production of ''N''-Acetylglutamate (NAG) from glutamate and acetyl-CoA. Put simply NAGS catalyzes the following reaction: :acetyl-CoA + L-glutamate → CoA + N-acetyl-L-glutamate NAGS, a member of the N-acetyltransferase family of enzymes, is present in both prokaryotes and eukaryotes, although its role and structure differ widely depending on the species. NAG can be used in the production of ornithine and arginine, two important amino acids, or as an allosteric cofactor for carbamoyl phosphate synthase (CPS1). In mammals, NAGS is expressed primarily in the liver and small intestine, and is localized to the mitochondrial matrix.〔A.J Meijer, C Lof, I.C Ramos, A.J Verhoeven, "Control of ureagenesis", Eur. J. Biochem., 148 (1985), pp. 189–196〕 ==Biological Function== Most prokaryotes (bacteria) and lower eukaryotes (fungi, green algae, plants, etc.) produce NAG through orinithine acetyltransferase (OAT), which is part of a ‘cyclic’ ornithine production pathway. NAGS is therefore used in a supportive role, replenishing NAG reserves as required. In some plants and bacteria, however, NAGS catalyzes the first step in a ‘linear’ arginine production pathway.〔Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. (1986) Biosynthesis and metabolism of arginine in bacteria. Microbiol. Rev. 50, 314–352〕 The protein sequences of NAGS between prokaryotes, lower eukaryotes and higher eukaryotes have shown a remarkable lack of similarity. Sequence identity between prokaryotic and eukaryotic NAGS is largely <30%,〔Yu, Y. G., Turner, G. E. and Weiss, R. L. (1996) Acetylglutamate synthase from Neurospora crassa: structure and regulation of expression. Mol. Microbiol. 22, 545–554〕 while sequence identity between lower and higher eukaryotes is ~20%.〔Caldovic, L., Mew, N. A., Shi, D., Morizono, H., Yudkoff, M., and Tuchmana, M. (2010) N-acetylglutamate synthase: structure, function and defects. Mol. Genet. Metab. 100(Suppl 1): S13–S19〕 Enzyme activity of NAGS is modulated by L-arginine, which acts as an inhibitor in plant and bacterial NAGS, but an effector in vertebrates.〔J Cybis, R.H Davis, Organization and control in the arginine biosynthetic pathway of Neurospora. J. Bacteriol., 123 (1975), pp. 196–202〕〔T Sonoda, M Tatibana, Purification of N-acetyl-l-glutamate synthetase from rat liver mitochondria and substrate and activator specificity of the enzyme. J. Biol. Chem., 258 (1983), pp. 9839–9844〕 While the role of arginine as an inhibitor of NAG in ornithine and arginine synthesis is well understood, there is some controversy as to the role of NAG in the urea cycle.〔Meijer, A. J. and Verhoeven, A. J. (1984) N-Acetylglutamate and urea synthesis. Biochem. J. 223, 559–560〕〔Lund, P. and Wiggins, D. (1984) Is N-acetylglutamate a short-term regulator of urea synthesis? Biochem. J. 218, 991–994〕 The currently accepted role of NAG in vertebrates is as an essential allosteric cofactor for CPS1, and therefore it acts as the primary controller of flux through the urea cycle. In this role, feedback regulation from arginine would act to signal NAGS that ammonia is plentiful within the cell, and needs to be removed, accelerating NAGS function. As it stands, the evolutionary journey of NAGS from essential synthetic enzyme to primary urea cycle controller is yet to be fully understood.〔Caldovic, L., Tuchman, M., N-Acetylglutamate and its changing role through evolution. Biochem. J. (2003) 372 (279–290) doi:10.1042/BJ20030002〕 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「N-Acetylglutamate synthase」の詳細全文を読む スポンサード リンク
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