Disease relevance of Asl

• ASL expression was time-dependently reduced in hypoxia [1].
• The regulation of AS and AL genes during hyperammonemia is unknown in the brain [2].
• The enzymes involved in citrulline-arginine metabolism, argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), and NOS were expressed in rat islets and insulinoma HIT T15 cells [3].
• The increased activities of ASS and ASL suggest the increased and effective recycling of citrulline to arginine in acute ammonia toxicity, making NO production more effective and contributing to its toxic effects [4].
• Rat argininosuccinate lyase was expressed in E. coli using pET-3a as a vector, and purified [5].

High impact information on Asl

• Argininosuccinate lyase (EC 4.3.2.1) is an enzyme of arginine biosynthesis and is also involved in the urea cycle in the liver of ureotelic animals [6].
• A comparison of cDNA-derived amino acid sequences revealed that argininosuccinate lyase is highly homologous with chicken delta-crystallin, a major structural protein of the eye lens [6].
• Coinduction of nitric oxide synthase, argininosuccinate synthetase, and argininosuccinate lyase in lipopolysaccharide-treated rats. RNA blot, immunoblot, and immunohistochemical analyses [7].
• Nitric oxide (NO) is synthesized from arginine by nitric oxide synthase (NOS), and citrulline which is generated can be recycled to arginine by argininosuccinate synthetase (AS) and argininosuccinate lyase (AL) [7].
• Our results show the urea cycle enzymes AS and AL confer cells with the capacity to produce NO without a need for exogenous arginine [8].

Chemical compound and disease context of Asl

• To understand the role of citrulline-NO cycle in hyperammonemia, NOS, ASS, ASL and arginase activities, as well as nitrate/nitrite (NOx), arginine, ornithine, citrulline, glutamine, glutamate and GABA were estimated in cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of rats subjected to acute ammonia toxicity [4].

Biological context of Asl

• Molecular cloning and nucleotide sequence of rat brain argininosuccinate lyase cDNA with an extremely long 5'-untranslated sequence: evidence for the identity of the brain and liver enzymes [9].
• Using as a probe rat liver argininosuccinate lyase cDNA, already isolated and sequenced (Amaya, Y., Matsubasa, T., Takiguchi, M., Kobayashi, K., Saheki, T., Kawamoto, S. and Mori, M., J. Biochem., 103 (1988) 177-181), we screened a rat brain cDNA library constructed in the lambda gt11 expression vector and obtained a single cDNA clone [9].
• Multiple copies of partial and inverted (antisense) B1 repeats and multiple upstream ATG codons are present in the region, which suggests a possibility of translational control of the argininosuccinate lyase gene expression in rat brain [10].
• Hypoxia did not affect ASL mRNA stability, indicating that this effect occurs at the transcriptional level [1].
• The ASL mRNA was first detectable on day 15.5 of gestation and increased in amount concomitantly with the rise in the enzyme activity, suggesting that the appearance of enzyme activity reflects the turning on of specific gene transcription [11].

Anatomical context of Asl

• Whereas AL is constitutive to vascular smooth muscle cells, AS mRNA and enzyme activity is markedly induced in cells by treatment with bacterial lipopolysaccharide (LPS) [8].
• Identification of argininosuccinate lyase as a hypoxia-responsive gene in rat hepatocytes [1].
• To find out whether NOS, ASS, and ASL are colocalized in neurons of the spinal cord, we examined the distribution of these enzymes by using a double-labeling procedure combining fluorescent immunohistochemistry with an assay for reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) [12].
• In this study, we evaluated the influence of hypobaric hypoxia on the expression of NOS isoforms, argininosuccinate synthetase (AS), argininosuccinate lyase (AL), and manganese superoxide dismutase (Mn SOD) in the ventilatory muscles [13].
• Argininosuccinate synthetase and argininosuccinate lyase are localized around mitochondria: an immunocytochemical study [14].

Associations of Asl with chemical compounds

• The enzymes of the urea cycle, including argininosuccinate lyase, are regulated developmentally and in response to dietary and hormonal changes, in a coordinated manner [15].
• Regeneration of arginine from citrulline is accomplished by two urea cycle enzymes: arginino-succinate synthetase (AS) and argininosuccinate lyase (AL) [8].
• In conjunction with NOS, citric acid cycle enzymes that covert fumarate to oxaloacetate (fumarase and malate dehydrogenase) and oxaloacetate to aspartate (aspartate transaminase), AS and AL form a novel arginine-citrulline cycle that enables high output NO production by cells [8].
• Messenger RNAs for carbamyl phosphate synthetase I, argininosuccinate synthetase, argininosuccinate lyase, and arginase increased in response to either dexamethasone or 8-(4-chlorophenylthio) cAMP (CPT-cAMP) [16].
• The effects of a combination of both hormones were additive for argininosuccinate lyase mRNA and synergistic for carbamyl phosphate synthetase I, argininosuccinate synthetase, and arginase mRNAs [16].

Regulatory relationships of Asl

• Insulin (1.8 X 10(-6)M) alone had no effect on the enzyme activities, but when incubated together with dexamethasone, it abolished the dexamethasone-induced increase of argininosuccinate synthetase and inhibited the argininosuccinate lyase activity by 80%, at 24 h [17].
• Glucagon did not induce any of the urea cycle enzymes in adrenalectomized Sprague-Dawley rats and only induced argininosuccinate lyase (EC 4.3.2.1) in adrenalectomized inbred Wistar-Furth rats [18].

Other interactions of Asl

• PURPOSE: Production of NO may be regulated by argininosuccinate synthetase and argininosuccinate lyase which recycle citrulline to arginine, and by arginase which hydrolyzes arginine to urea and ornithine [19].
• Changes in levels of argininosuccinate lyase mRNA during induction by glucagon and cyclic AMP in cultured foetal-rat hepatocytes [20].
• Expression of prostacyclin synthase and argininosuccinate lyase, secondary enzymes of NO- and prostanoid-forming pathways, was not stimulated by db-cAMP [21].
• We also measured mRNA expression of GTP cyclohydrolase I, the rate-limiting enzyme in the synthesis of NOS cofactor, tetrahydrobiopterin, and mRNA and protein expressions of argininosuccinate synthase and argininosuccinate lyase, essential enzymes for the recycling of L-citrulline to L-arginine [22].
• Ornithine carbamoyltransferase, arginosuccinate synthase, argininosuccinate lyase and glutamate dehydrogenase (NAD(P)+) were not affected by dietary vitamin E or by DEM/BrCCl3 [23].

Analytical, diagnostic and therapeutic context of Asl

• Northern-blot analysis revealed that these agents only gave a transient induction of ASL mRNA amount, which reached a peak at 6 h and declined thereafter [20].
• Expression of urea synthesis, as reflected by carbamoylphosphate synthetase mRNA, showed a gradual decline after 90% hepatectomy, in contrast to rising levels of argininosuccinate lyase and arginase mRNA, possibly serving polyamine rather than urea synthesis [24].
• Using RNase protection assay and non-radioactive in situ hybridization on aggregate cryosections, we show that both AS and AL genes are induced in astrocytes but not in neurons of aggregates exposed to 5 mM NH4Cl [2].
• Hyperammonemia: regulation of argininosuccinate synthetase and argininosuccinate lyase genes in aggregating cell cultures of fetal rat brain [2].
• To this end, ASL was purified, an ELISA assay was established to quantify the enzyme protein and a cDNA clone was used to measure the amount of specific mRNA in the liver in various stages of development [25].

References