Disease relevance of Ass1

• The absence of citrin leads to a liver-specific, quantitative decrease of argininosuccinate synthetase (ASS), causing hyperammonemia and citrullinemia [1].
• We demonstrated that the neonatal crisis in Ass mice can be ameliorated by the injection of a recombinant adenovirus carrying human AS cDNA (Ad.CMVhAS) within hours after birth [2].
• Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivation via arginine deiminase [3].
• Recently, pegylated arginine deiminase (ADI; EC 3.5.3.6) has been used to treat the patients with hepatocellular carcinoma or melanoma, in which the level of argininosuccinate synthetase (ASS) activity is low or undetectable [3].
• Based on our results, we suggest that immunization of AD patients with Ass should be done with caution as the increase in Ass could trigger the brain inflammation in uncontrollable level [4].

Psychiatry related information on Ass1

• LRP-1, although abundant in brain microvessels in young mice, was downregulated in older animals, and this downregulation correlated with regional Ass accumulation in brains of Alzheimer's disease (AD) patients [5].

High impact information on Ass1

• There was no evidence that Ass was metabolized in brain interstitial fluid and degraded to smaller peptide fragments and amino acids before its transport across the BBB into the circulation [5].
• Hepatocellular carcinoma (HCC) is believed to be auxotrophic for arginine through the lack of expression of argininosuccinate synthetase (ASS) [6].
• Citrulline, which is the coproduct of NOS-catalyzed metabolism of arginine, can be recycled to arginine by the action of argininosuccinate synthetase and argininosuccinate lyase, which are present at high levels in hepatocytes and renal tubular cells but normally at very low levels in other cell types such as macrophages [7].
• The present study demonstrates that lipopolysaccharide and interferon-gamma, which induce NOS in the murine macrophage cell line RAW 264.7, also coinduce activity and mRNA for argininosuccinate synthetase, which is limiting for arginine synthesis [7].
• Coinduction of nitric oxide synthase and argininosuccinate synthetase in a murine macrophage cell line. Implications for regulation of nitric oxide production [7].

Chemical compound and disease context of Ass1

• However, when the glioma cells were treated with either bacterial lipopolysaccharide, interferon-gamma, or a combination of both, argininosuccinate synthetase immunoreactivity was increased [8].

Biological context of Ass1

• Crat mapped to Chromosome (Chr) 2, at a position approximately 18 cM from the centromere and 2 cM proximal to the gene Ass1 [9].
• In order to develop linkage markers for the murine argininosuccinate synthetase locus (Ass-1), we have searched for restriction fragment length polymorphisms in the mouse genome using cloned sequences from the mouse arginosuccinate synthetase structural gene [10].
• Immunoblot analysis showed that iNOS, argininosuccinate synthetase, and arginase I and II proteins were induced with similar kinetics as those of their respective mRNAs [11].
• The internal amino acid sequences of the protein were identical with those of argininosuccinate synthase (EC 6.3.4.5) [12].
• Argininosuccinate synthase also inhibited the biological activities (macrophage activation and Limulus test) of natural lipid A and rough-type LPS but not smooth-type LPS [12].

Anatomical context of Ass1

• We have used homologous recombination in embryonic stem cells to generate a line of mice having a targeted disruption of the Ass gene [13].
• Presence of argininosuccinate synthetase in glial cells as revealed by peptide-specific antisera [8].

Associations of Ass1 with chemical compounds

• Carnitine administration relieved the suppression of the developmental induction of two urea cycle enzymes examined, carbamoyl-phosphate synthetase and argininosuccinate synthase, and kept the activities of enzymes normal [14].
• Argininosuccinate synthetase (ASS) is a urea cycle enzyme that forms argininosuccinate from citrulline and aspartate [13].
• Induction of argininosuccinate synthetase is not blocked by NG-monomethyl-L-arginine, a potent inhibitor of NOS, indicating that argininosuccinate synthetase induction is not the consequence of depleting cellular arginine levels by NOS [7].
• Circulating arginine available for synthesis of protein is produced in the kidney of the adult mammal by the action of the last two enzymes of the urea cycle, argininosuccinate synthase and argininosuccinate lyase [15].
• Argininosuccinate synthetase and argininosuccinate lyase catalyze the conversion of citrulline to arginine in kidney [16].

Other interactions of Ass1

• The strain distribution pattern for this polymorphism indicated close linkage of Ass-1 to Hc (the fifth component of complement) on proximal mouse chromosome 2 with a recombination fraction of 0.016 and a 95% confidence interval of 0.003 to 0.054 [10].
• In contrast, these agents consistently inhibit induction of argininosuccinate synthetase mRNA in both LPS- and IFN-gamma-stimulated cells [17].

Analytical, diagnostic and therapeutic context of Ass1

• Oral administration of one of these compounds, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, to mice transgenic for human APP(V717F) reduces brain levels of Ass in a dose-dependent manner within 3 h [18].
• Native gel electrophoresis of a mixture of argininosuccinate synthase and LPS and immunoprecipitation of a mixture of argininosuccinate synthase and [(3)H]-LPS with anti-argininosuccinate synthase antiserum showed that argininosuccinate synthase stably bound lipid A and LPS [12].

References