Cloning and expression of the human N-acetylglutamate synthase gene

• Published in: Biochemical and biophysical research communications Vol. 299; no. 4; pp. 581 - 586
• Main Authors: Caldovic, Ljubica, Morizono, Hiroki, Gracia Panglao, Maria, Gallegos, Rene, Yu, Xiaolin, Shi, Dashuang, Malamy, Michael H, Allewell, Norma M, Tuchman, Mendel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13-12-2002
• Subjects: Acetyltransferases - genetics; Acetyltransferases - metabolism; Amino Acid Sequence; Amino-Acid N-Acetyltransferase; Animals; ARG2; ArgA; Arginine metabolism; Carbamylphosphate synthetase I; Cloning, Molecular; Gene Library; Genetic Complementation Test; Humans; Liver - physiology; Mice; Molecular Sequence Data; NAT7; Open Reading Frames; Protein Structure, Tertiary; Recombinant Proteins - metabolism; Sequence Alignment; Tissue Distribution; Urea cycle; ARG2; NAT7; Urea cycle; ArgA; Arginine metabolism; Carbamylphosphate synthetase I
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(02)02696-7

N-acetylglutamate synthase (NAGS, E.C. 2.3.1.1) is a mitochondrial enzyme catalyzing the formation of
N-acetylglutamate (NAG), an essential allosteric activator of carbamylphosphate synthase I (CPSI), the first enzyme of the urea cycle. Patients with NAGS deficiency develop hyperammonemia because CPSI is inactive without NAG. The human NAGS cDNA was isolated from a liver library based on its similarity to mouse NAGS. The deduced amino acid sequence contains an N-terminal putative mitochondrial targeting signal of 49 amino acids (63% identity with mouse NAGS) followed by a “variable domain” of 45 amino acids (35% identity) and a “conserved domain” of 440 amino acids (92% identity). A cDNA sequence containing the “conserved domain” complements an NAGS-deficient
Escherichia coli strain and the recombinant protein has arginine-responsive NAGS catalytic activity. The NAGS gene is expressed in the liver and small intestine; the intestinal transcript is smaller in size than liver transcript.