期刊
BIOCHEMICAL JOURNAL
卷 372, 期 -, 页码 279-290出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20030002
关键词
arginine biosynthesis; urea cycle; carbamylphosphate synthetase I; hyperammonaemia; N-acetylglutamate synthase; ornithine acetyltransferase
资金
- NCRR NIH HHS [M01RR13297] Funding Source: Medline
- NICHD NIH HHS [HD 40677, HD32652] Funding Source: Medline
- NIDDK NIH HHS [DK47870, R01 DK064913] Funding Source: Medline
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 enzymic 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. In humans, inherited NAGS deficiency is an autosomal recessive disorder causing hyperammonaemia and a phenotype similar to CPSI deficiency. Several mutations have been-recently identified in the NAGS genes of families affected with this disorder.
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