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Query: EC:4.4.1.1 (cystathionine gamma-lyase)
 528 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cystathionine was cleaved into 2-ketobutyric acid, cysteine and ammonia by cystathionase. 2-Ketobutyric acid was converted into 3-ethyl-2-hydroxy-6,7-dimethoxyquinoxaline (EHDQ) by reaction with 1,2-diamino-4,5-dimethoxybenzene. When EHDQ was measured in a mobile phase of pH 2.1 using high-performance liquid chromatography with ultraviolet detection, 250 pmol of L-cystathionine in 250 microliters of the reaction mixture could be determined. Because EHDQ has a strong fluorescence in a mobile phase of pH 6.5 at 447 nm, on excitation at 365 nm, as little as 2.5 pmol of cystathionine in 250 microliters of the reaction mixture could be determined by high-performance liquid chromatography with fluorimetric detection. Cystathionase activity was assayed on the basis of the same principle by determining cystathionine in as little as 63 ng of rat liver by fluorimetric detection. Cystathionine beta-synthase activity was measured by the same method by determining cystathionine formed in only 113 ng of wet weight of rat liver. Using these methods, both cystathionine beta- and gamma-lyase activities in Saccharomyces cerevisiae were determined, because quinoxaline derivatives from pyruvate and 2-ketobutyrate could be measured simultaneously by high-performance liquid chromatography.
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PMID:Sensitive determination of cystathionine and assays for cystathionine beta- and gamma-lyase, as well as cystathionine beta-synthase, using high-performance liquid chromatography. 162 86

Glutathione-deficient mutants (gshA) of the yeast Saccharomyces cerevisiae, impaired in the first step of glutathione (GSH) biosynthesis were studied with respect to the regulation of enzymes involved in GSH catabolism and cysteine biosynthesis. Striking differences were observed in the content of the sulphur amino acids when gshA mutants were compared to wild-type strains growing on the same minimal medium. Furthermore, all mutants examined showed a derepression of gamma-glutamyltranspeptidase (gamm-GT), the enzyme initiating GSH degradation. However, gamma-cystathionase and cysteine synthase were unaffected by the GSH deficiency as long as the nutrient sulphate source was not exhausted. The results suggest that the mutants are probably not impaired in the sulphate assimilation pathway, but that the gamma-glutamyl cycle could play a leading role in the regulation of the sulphur fluxes. Studies of enzyme regulation showed that the derepression of gamma-GT observed in the gshA strains was most probably due to an alteration of the thiol status. The effectors governing the biosynthesis of cysteine synthase and gamma-cystathionase seemed different from those playing a role in gamma-GT regulation and it was only under conditions of total sulphate deprivation that all these enzymes were derepressed. As a consequence the endogenous pool of GSH was used in the synthesis of cysteine. GSH might, therefore, fulfil the role of a storage compound.
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PMID:Glutathione as an endogenous sulphur source in the yeast Saccharomyces cerevisiae. 167 26

Eight classes of pyridoxal 5'-phosphate dependent enzymes have been investigated in Nippostrongylus brasiliensis in parallel with rat tissues. The range of decarboxylases detected in N. brasiliensis was limited in comparison with rat tissues. N. brasiliensis possessed a highly active L-serine hydroxymethyltransferase, but in contrast with rat liver, 5-aminolevulinic acid synthetase was absent. Similar levels of L-serine and L-threonine dehydratase activities were detected in N. brasiliensis and rat liver, and both organisms lacked L-alanine racemase, L-tryptophan synthetase and L-methionine gamma-lyase. The demonstration of cystathionine beta-synthase and gamma-cystathionase in N. brasiliensis suggests the presence of a functional trans-sulphuration sequence. The substrate specificities of the nematode cystathionine beta-synthase and gamma-cystathionase varied significantly from those of the corresponding mammalian enzymes. Particularly striking was the ability of N. brasiliensis cystathionine beta-synthase to catalyse the non-mammalian 'activated L-serine sulphydrase' reaction (L-cysteine + R-SH----cysteine thioether + H2S). N. brasiliensis and rat liver exhibited comparable abilities to transaminate amino acids via the 2-oxoglutarate: glutamate system.
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PMID:Pyridoxal 5'-phosphate dependent enzymes in the nematode Nippostrongylus brasiliensis. 175 92

The activities of gamma-cystathionase and cystathionine beta-synthase were investigated in a range of gastrointestinal, free-living and entomophagous nematodes. Although nematode gamma-cystathionase used the same range of substrates as the mammalian hepatic enzyme, its activity was extremely low and there were significant interspecies variations with respect to the relative order of active substrates. Like the mammalian liver enzyme, nematode cystathionine beta-synthase showed activity in the directions of both cystathionine synthesis and the forward and reverse "L-serine sulphhydrase" reactions. However, the most important feature of the survey was the widespread ability of nematode cystathionine beta-synthase to catalyse the non-mammalian "activated L-serine sulphhydrase" reaction (L-cysteine + R-SH----cysteine thioether + H2S). Additional survey work revealed that the ability to catalyse the activated L-serine sulphhydrase reaction was almost universal amongst nematodes. Activated L-serine sulphhydrase activity was also demonstrated in the acanthocephalan Pomphorhynchus laevis but was absent from cestodes and digeneans.
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PMID:Cystathionine beta-synthase and gamma-cystathionase in helminths. 180 16

Amino acid solutions currently used for total parenteral nutrition (TPN) contain little cysteine or cystine. Some premature human infants have low liver activities of gamma-cystathionase and presumably require preformed cysteine or cystine. Growing animals tend to have higher liver gamma-cystathionase activity, which makes them unsuitable as models to study effects of CSH precursors. Because propargylglycine (PPG) inhibits gamma-cystathionase specifically, rats infused with PPG as part of a TPN regimen were evaluated as a potential model. Two groups of rats (120-160 g) were infused for 15 d with TPN regimens, one without and one with PPG (40 mumols/d). A third group received the TPN-control regimen, with methionine added at toxic levels. Propargylglycine treatment significantly decreased plasma cystine and taurine concentrations and significantly increased plasma cystathionine concentration without affecting methionine concentration. Propargylglycine treatment significantly decreased brain, muscle, liver, intestine and stomach glutathione concentration without affecting erythrocyte or heart glutathione concentrations. Electron microscopic examination showed no abnormalities in heart and kidney of PPG-treated rats. Hepatocyte glycogen was lower in TPN-fed controls than in orally fed rats and was further reduced in TPN-PPG-fed animals. Growing rats infused with low doses of PPG show promise as an animal model to study a number of important issues concerning human sulfur amino acid metabolism.
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PMID:Propargylglycine infusion effects on tissue glutathione levels, plasma amino acid concentrations and tissue morphology in parenterally-fed growing rats. 203 64

Both cysteinesulfinate-independent and cysteinesulfinate-dependent pathways are involved in the catabolism of cyst(e)ine by freshly isolated rat renal cortical tubules. Sulfate and thiosulfate were shown to be the major sulfur-containing products that accumulated in incubations of renal tubules with 1 mmol/L or 25 mmol/L [35S]cyst(e)ine. Thiosulfate is an intermediate in the oxidation of the sulfide produced by the cysteinesulfinate-independent catabolism of cyst(e)ine by desulfhydration pathway(s), whereas sulfate is formed both by further oxidation of thiosulfate and by oxidation of the sulfite formed by the cysteinesulfinate-transamination pathway. Incubation of renal tubules with propargylglycine inhibited gamma-cystathionase activity by 85%, and this resulted in a 46% decrease in sulfate production and a 68% decrease in thiosulfate production when the treated renal tubules were incubated with 1 mmol/L [35S]cyst(e)ine. Addition of 25 mmol/L unlabeled cysteinesulfinate to create a diluting/trapping pool for [35S]cysteinesulfinate formed from [35S]cysteine resulted in a 53% decrease in [35S]sulfate production in incubations with 1 mmol/L cysteine. Thus, some cyst(e)ine catabolism probably occurred by a cysteinesulfinate-dependent pathway. No production of taurine or hypotaurine was detected in incubations with cyst(e)ine. Thus, cysteinesulfinate formed from cysteine was further catabolized primarily to sulfate instead of to taurine and hypotaurine. Most cyst(e)ine catabolism by the epithelial cells of the renal tubule probably can be accounted for by two pathways: 1) the beta-cleavage of cystine catalyzed by lambda-cystathionase and 2) the formation and transamination of cysteinesulfinate catalyzed by cysteine dioxygenase and aspartate aminotransferase.
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PMID:Catabolism of cyst(e)ine by rat renal cortical tubules. 211 78

To assess the extent to which low hepatic gamma-cystathionase levels affect methionine flux to cysteine in hepatocytes, the effect of inhibition of gamma-cystathionase activity with propargylglycine on the metabolism of L-[35S]methionine was determined in studies with freshly isolated rat hepatocytes. gamma-Cystathionase activity was inhibited 25%, 42%, 63% and 76% (maximal inhibition) by treatment with 2.5 mumol/L, 0.01 mmol/L, 0.02 mmol/L and 2 mmol/l propargylglycine, respectively. Inhibition of gamma-cystathionase activity with up to 0.02 mmol/L propargylglycine had no statistically significant effect on [35S]glutathione, [35S]sulfate or [35S]cysteine formation from [35S]methionine. However, treatment of cells with 2 mmol/L propargylglycine markedly inhibited the metabolism of [35S]methionine to [35S]glutathione by 93%, to [35S]sulfate by 88% and to [35S]cysteine by 89%; [35S]cystathionine accumulation in these incubation systems was 60 times control. Hepatic gamma-cystathionase activity in premature infants has been reported to be about 23% of mature levels (Zlotkin and Anderson, 1982; Pediatr. Res. 16: 65-68); this level of gamma-cystathionase activity may limit cysteine synthesis by the methionine transsulfuration pathway. No evidence for cysteine synthesis from serine and sulfide, which can be catalyzed by cystathionine beta-synthase, or for methionine metabolism by an S-adenosylmethionine-independent pathway was obtained.
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PMID:Role of the transsulfuration pathway and of gamma-cystathionase activity in the formation of cysteine and sulfate from methionine in rat hepatocytes. 211 6

The metabolism of L-cysteine was studied in freshly isolated rat hepatocytes. Because cysteine is rapidly oxidized in oxygenated incubation medium at neutral pH, the effect of bathocuproine disulfonate, a copper-specific chelator, was investigated. Addition of bathocuproine disulfonate resulted in a higher extracellular cysteine-to-half-cystine ratio in incubations of hepatocytes with cysteine. Bathocuproine disulfonate also increased the total uptake and metabolism of cysteine plus cystine [cyst(e)ine] by hepatocytes, which is consistent with the more efficient transport of cysteine than of cystine by freshly isolated rat hepatocytes. The partitioning of cysteine between cysteinesulfinate-dependent and cysteinesulfinate-independent pathways of catabolism was also altered by the addition of bathocuproine disulfonate; the percentage of total catabolic flux that resulted in taurine plus hypotaurine formation was greater, and the percentage of total catabolic flux that occurred by the beta-cleavage of cystine in a reaction catalyzed by gamma-cystathionase was less in incubations that contained bathocuproine disulfonate. Thus addition of bathocuproine disulfonate to maintain a higher extracellular thiol-to-disulfide ratio favored cysteinesulfinate-dependent catabolism of cysteine in rat hepatocytes.
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PMID:Effect of bathocuproine disulfonate, a copper chelator, on cyst(e)ine metabolism by freshly isolated rat hepatocytes. 239 77

The addition of L-cysteine to hepatic cytosols causes inactivation of tyrosine aminotransferase. We have studied the mechanism of inactivation and the effect of streptozotocin-induced diabetes in the rat on the inactivation of tyrosine aminotransferase in the presence of fractions prepared from livers and kidneys. Diabetes increased the rate at which tyrosine aminotransferase was inactivated after addition of cysteine to hepatic cytosols. The inactivation was due to the production of thiocysteine (which contains sulfane sulfur) from cystine as a result of desulfuration catalyzed by gamma-cystathionase. Diabetes increased the content of cystathionine beta-synthase and gamma-cystathionase in liver. As a result, cytosols from diabetic animals converted homocysteine, cystathionine, cysteine and cystine to sulfane at an elevated rate, with resulting inactivation of tyrosine aminotransferase. In contrast, inactivation in kidney fractions was not affected by diabetes. Incubation with an inhibitor of gamma-cystathionase (propargylglycine) prevented inactivation of tyrosine aminotransferase. These results show that the potential for the formation of sulfane sulfur by the enzymes of the transsulfuration pathway is enhanced by chronic diabetes.
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PMID:Experimental diabetes increases the formation of sulfane by transsulfuration and inactivation of tyrosine aminotransferase in cytosols from rat liver. 256 58

Cyst(e)ine was metabolized by rat enterocytes to pyruvate and inorganic sulfur but not to taurine. Cystine was the major extracellular form of cyst(e)ine present during the incubation, and addition of bathocuproine disulfonate, a copper chelator that maintained 60% of the total cyst(e)ine in the sulfhydryl form, had no effect on total sulfur release from cyst(e)ine. Oxidation of cyst(e)ine to 35SO4(2-) or 14CO2 was reduced by about 50% when unlabeled cysteinesulfinate was added to incubations of enterocytes with labeled cyst(e)ine. Thus, about one half of cyst(e)ine metabolism appeared to involve its oxidation to cysteinesulfinate and the transamination of cysteinesulfinate to the putative intermediate sulfinylpyruvate, which decomposes to yield sulfite and pyruvate. The remainder of cyst(e)ine catabolism in enterocytes appeared to involve release of sulfur from cyst(e)ine prior to its oxidation. Inhibition of gamma-cystathionase by propargylglycine, although incomplete, resulted in substantial inhibition of cyst(e)ine catabolism. The accumulation of cysteinethiosulfonate, which forms nonenzymatically upon incubation of cyst(e)ine with thiosulfate, and the inhibition of cysteinethiosulfonate formation by propargylglycine demonstrated the catabolism of cyst(e)ine by beta-cleavage catalyzed by gamma-cystathionase. Sulfide released from cyst(e)ine in this reaction appeared to be oxidized to thiosulfate before it was further oxidized to sulfite and sulfate. In addition to being oxidized to sulfate, some of the sulfite formed by enterocytes reacted with cyst(e)ine in the incubation medium to form sulfocysteine. Activities of enzymes of cyst(e)ine catabolism in rat enterocytes corresponded with the observed metabolism of cyst(e)ine by various pathways.
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PMID:Metabolism of cyst(e)ine in rat enterocytes. 262 85


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