Disease relevance of N-Acetylglutamate

• Inhibition by propionyl-coenzyme A of N-acetylglutamate synthetase in rat liver mitochondria. A possible explanation for hyperammonemia in propionic and methylmalonic acidemia [1].
• Nucleotide sequence of the Bacillus subtilis argC gene encoding N-acetylglutamate-gamma-semialdehyde dehydrogenase [2].
• Sequencing analysis of the gene showed that it encodes a 322-residue polypeptide that is homologous to the ArgC protein of E. coli, Bacillus subtilis and Streptomyces clavuligerus and to the C-terminal moiety of the Saccharomyces cerevisiae ARG5,6 gene product, N-acetylglutamate semialdehyde dehydrogenase [3].
• Use of inducible feedback-resistant N-acetylglutamate synthetase (argA) genes for enhanced arginine biosynthesis by genetically engineered Escherichia coli K-12 strains [4].
• Regulation of N-acetylglutamate synthesis in Salmonella typhimurium [5].

High impact information on N-Acetylglutamate

• Glutamine- and N-acetylglutamate-dependent carbamoyl phosphate synthetase in elasmobranchs [6].
• A decreased level of N-acetylglutamate in liver mitochondria that would follow inhibition of N-acetylglutamate synthetase by propionyl-CoA would be expected to lead to hyperammonemia [1].
• Its activator, N-acetylglutamate, is synthesized from acetyl-CoA and glutamate in a reaction catalyzed by N-acetylglutamate synthase (NAGS) [7].
• Experiments with isolated mitochondria showed that approximately 60-70% of external [U-(15)N(4)]arginine catabolism was recovered as (15)N-labeled ornithine, glutamate, N-acetylglutamate, citrulline, and aspartate [8].
• The glucagon-induced increase in [(15)N]urea synthesis was associated with a significant elevation in hepatic N-acetylglutamate concentration [9].

Chemical compound and disease context of N-Acetylglutamate

• A very high and thermostable N-acetylglutamate 5-phosphotransferase activity was detected in extracts of E. coli arg B mutants transformed with the 3.4 kb fragment on a plasmid [10].

Biological context of N-Acetylglutamate

• N-Acetylglutamate is present in foetal rat liver at 17 days' gestation [11].
• In strain NE1 of Tn5-1058-mutagenized Nostoc ellipsosporum, the transposon was found within a gene whose translation product is similar in amino acid sequence to the arginine-biosynthetic protein N-acetylglutamate semialdehyde dehydrogenase encoded by argC of Bacillus subtilis [12].
• We describe here a concise assay procedure for N-acetylglutamate (AGA) synthase (AGAS) and its application to an extensive study of tissue distribution of AGAS activity [13].
• Archaeal argJ only complements an Escherichia coli argE mutant (deficient in acetylornithinase, which catalyzes the fifth step in the linear biosynthetic pathway), whereas bacterial genes additionally complement an argA mutant (deficient in N-acetylglutamate synthetase, the first enzyme of the pathway) [14].
• In a subsequent step on ITLC-SG ready plates N-acetylglutamate is separated from other labeled metabolites such as Krebs cycle intermediates [15].

Anatomical context of N-Acetylglutamate

• Carbamyl phosphate synthetase I (EC 2.7.2.5) activity, assayed in intact mitochondria isolated from livers removed 15 min after injection of amino acids, with N-acetylglutamate at its endogenous levels, rose up to 5-fold with increasing doses up to 2 g/kg; no further activation occurred with larger doses [16].
• N-Acetylglutamate content of hepatocytes from 48 h-starved rats is high [17].
• In addition, we failed to detect in liver and small intestine alpha-N-acetylornithine, N-acetylglutamate kinase or N-acetylornithine aminotransferase, which are obligatory components of a potential route of ornithine synthesis from N-acetylglutamate [18].
• The permeability properties of the rat-liver mitochondrial membrane for N-acetylglutamate, the activator of carbamoyl-phosphate synthetase (ammonia), were studied [19].
• This behaviour is in accordance with the physiological requirement for efflux of N-acetylglutamate from the mitochondria in order to be degraded in the cytosol [19].

Associations of N-Acetylglutamate with other chemical compounds

• If in vivo the constants are of the same order of magnitude as in vitro, the synthesis of N-acetylglutamate, an obligate activator of the first step of urea synthesis, can be expected to occur in the mitochondrion under conditions where the amino acid acetyltransferase is not saturated by its substrates [20].
• These observations indicate that the increased N-acetylglutamate content was not due to an increase in glutamate content caused by an activation of glutaminase (EC 3.5.1.2) [21].
• The N-acetylglutamate synthase/N-acetylglutamate kinase metabolon of Saccharomyces cerevisiae allows co-ordinated feedback regulation of the first two steps in arginine biosynthesis [22].
• After the addition of ATP and N-acetylglutamate to uncoupled mitochondria, no inhibition could be demonstrated with dipropylacetate and 4-pentenoate [23].
• In Saccharomyces cerevisiae, argB and argC define two adjacent and complementing loci, with mutants defective in two consecutive steps of arginine biosynthesis: N-acetylglutamate kinase (AG-kinase) and N-acetylglutamyl-phosphate reductase (AGPreductase) [24].

Gene context of N-Acetylglutamate

• Feedback inhibition of the corresponding N-acetylglutamate kinase activity was observed both in cell extracts of C. glutamicum and in recombinant E. coli argB auxotrophic strains [25].
• N-Acetylglutamate synthase (NAGS, EC 2.3.1.1) is a mitochondrial enzyme that catalyzes the formation of N-acetylglutamate (NAG) from glutamate and acetylcoenzyme A [26].
• A second gene (argB) encoding another amino-acid biosynthetic enzyme, N-acetylglutamate kinase, was identified upstream of, and on the opposite strand to the gene encoding ALS (ilvB) [27].
• Enzyme activity and size of the expressed protein in the E. coli auxotroph carrying the recombinant argC gene revealed that the cloned gene indeed codes for N-acetylglutamate 5-semialdehyde dehydrogenase [28].
• Its localization in the periplasmic space explains the inability of P. aeruginosa argA mutants to grow on N-acetylglutamate, which is utilized by the wild-type as a carbon and nitrogen source [29].

Analytical, diagnostic and therapeutic context of N-Acetylglutamate

• N-Acetylglutamate 5-phosphotransferase (acetylglutamate kinase, EC 2.7.2.8) has been isolated from pea (Pisum sativum) cotyledons and purified 312-fold by using heat treatment, (NH4)2SO4 fractionation, affinity chromatography on ATP--Sepharose and ion-exchange chromatography on DEAE-cellulose [30].
• The apparent Michaelis constant values for N-acetylglutamate, ammonia, and ATP were not significantly changed by immobilization [31].

References