Cloning and expression of the human N-acetylglutamate synthase gene

Biochem Biophys Res Commun. 2002 Dec 13;299(4):581-6. doi: 10.1016/s0006-291x(02)02696-7.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetyltransferases / genetics*
  • Acetyltransferases / metabolism
  • Amino Acid Sequence
  • Amino-Acid N-Acetyltransferase
  • Animals
  • Cloning, Molecular
  • Gene Library
  • Genetic Complementation Test
  • Humans
  • Liver / physiology
  • Mice
  • Molecular Sequence Data
  • Open Reading Frames
  • Protein Structure, Tertiary
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Tissue Distribution

Substances

  • Recombinant Proteins
  • Acetyltransferases
  • Amino-Acid N-Acetyltransferase
  • NAGS protein, human
  • Nags protein, mouse

Associated data

  • GENBANK/AY158070