Disease relevance of NAGS

• Null mutations in the N-acetylglutamate synthase gene associated with acute neonatal disease and hyperammonemia [1].
• A 6-year-old boy with hyperammonaemia: partial N-acetylglutamate synthase deficiency or portosystemic encephalopathy [2]?
• Brachytherapy in total coronary occlusions: Quidquid agis, prudenter agas, et respice finem [3].

High impact information on NAGS

• Its activator, N-acetylglutamate, is synthesized from acetyl-CoA and glutamate in a reaction catalyzed by N-acetylglutamate synthase (NAGS) [4].
• N-Acetyl-L-glutamate (N-acetylglutamate) content and N-acetylglutamate synthase activity ranges were established in human liver tissue homogenates by stable isotope dilution [5].
• The regulation of the first step of urea synthesis could thus depend mainly on the intramitochondrial substrate and perhaps product concentrations of amino acid acetyltransferase [6].
• 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 [6].
• Acetyl-CoA:L-glutamate N-acetyltransferase (amino acid acetyltransferase, EC 2.3.1.1) was isolated from human liver mitochondria by precipitation with (NH4)2SO4 and chromatography on hydroxyapatite, DEAE-cellulose and Sephacryl 300 [6].

Biological context of NAGS

• In order to evaluate the impact of an urban effluent on antibiotic resistance of freshwater bacterial populations, water samples were collected from the Arga river (Spain), upstream and downstream from the wastewater discharge of the city of Pamplona [7].
• 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 [8].
• This method (CASSOH-ELISA) has been successfully applied for the detection of clinically important SNPs in drug metabolism, such as N-acetyltransferase 2, NAT26 (590G>A) and NAT7 (857G>A), and mitochondrial DNA (1555A>G) [9].
• Diagnosis of N-acetylglutamate synthase deficiency by use of cultured fibroblasts and avoidance of nonsense-mediated mRNA decay [10].

Anatomical context of NAGS

• Enzymological evidence for the indispensability of small intestine in the synthesis of arginine from glutamate. II. N-acetylglutamate synthase [8].
• An extensive survey of AGAS activity in rats showed that, although the liver expressed the highest activity, the small intestine, testis, lung and submaxillary gland also exhibited considerable activity [8].

Associations of NAGS with chemical compounds

• N-acetylglutamate synthase (NAGS) is a mitochondrial enzyme that catalyzes the formation of N-acetylglutamate, an essential allosteric activator of carbamyl phosphate synthetase I, the first enzyme of the urea cycle [1].
• 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 [11].
• Restoration of ureagenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate [12].
• Among the gene products that were actively synthesized in the symbiotic system of the young host were putative aspartate aminotransferase, homoserine kinase and N-acetylglutamate synthase [13].
• Further study is needed to fully identify their mode of preventing AGAS and, more important, to determine their usefulness and role in preventing AGAS, especially since concurrent HMG-CoA reductase inhibitor use with cyclosporine is not innocuous [14].

References