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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 beta-synthase and gamma-cystathionase, the two major enzymes of the transsulfuration pathway of methionine metabolism, are described. These enzymes are responsible for inborn errors, e.g., homocystinuria and cystathioninuria. The interaction of gamma-cystathionase with the cofactor, substrates and inhibitors of the general formula RONH2 containing structural fragments of substrates has been studied. A non-radioactive avidin-biotin system for the microdetection of gamma-cystathionase in dot blots has been developed. This system was applied for immunoscreening of a rat liver cDNA library in the prokaryotic expression vector lambda gt 11.
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PMID:[Pyridoxal phosphate-dependent enzymes of sulfur amino acid metabolism]. 275 77

Tyrosine aminotransferase is stable in homogenates of rat liver, but not when L-cystine or L-cysteine is added, which causes the enzyme to be reversibly inactivated due to oxidation of thiol groups. By monitoring inactivation of the aminotransferase in the presence of L-cystine, a factor responsible for this loss of activity was purified from rat liver. The factor required vitamin B6 and co-purified with gamma-cystathionase during numerous steps. Highly purified inactivating factor contained a protein that was identical in size and isoelectric point to cystathionase but also contained a dissimilar peptide that appeared to be unrelated to cystathionase. Cystathionase and the cystine-dependent inactivator shared several catalytic activities, including the hydrolysis of cystathionine, desulfuration of cystine, and desulfhydration of cysteine. During incubation of L-cysteine with the purified factor, hydrogen sulfide was generated but no inactivation of the aminotransferase occurred, suggesting that cysteine-dependent inactivation requires additional mechanisms. An insoluble inactivator of tyrosine aminotransferase that is produced during the reaction may be elemental sulfur, since colloidal suspensions of sulfur also inhibited the enzyme. Another inhibitor fractionated with high molecular weight substances; this may be protein-bound sulfane.
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PMID:A cystine-dependent inactivator of tyrosine aminotransferase co-purifies with gamma-cystathionase (cystine desulfurase). 288 19

The major pathways for cysteine catabolism in Hymenolepis diminuta have been investigated. The parasite has an active cystathionine-beta-synthase and, as in other tissues, this enzyme has a wide substrate specificity. However, the enzyme from H. diminuta differs significantly from the mammalian enzyme in showing a high serine sulphydrase activity and a high serine lyase activity. There was only low gamma-cystathionase activity in H. diminuta and again the enzyme showed a range of substrate specificities. Cysteine aminotransferase activity was readily demonstrated in the tapeworm, but there was no evidence for 3-mercaptopyruvate sulphotransferase activity. An oxidative pathway for cysteine catabolism in H. diminuta was shown by the presence of cysteine dioxygenase and cysteine sulphinate transaminase. The properties of the helminth cysteine dioxygenase were very similar to those of rat liver. H. diminuta was able to reduce cystine to cysteine via a glutathione-cysteine transhydrogenase system.
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PMID:Cysteine metabolism in the cestode Hymenolepis diminuta. 317 34

The rapid method for gamma-cystathionase purification was developed. It is based on the non-ideal gel filtration HPLC. The isolated homogeneous enzyme was used for immunization and immunosorbent preparation. A monospecific polyclonal antibody was prepared. The substrate specificity of the isolated enzyme was studied.
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PMID:[Gamma-cystathionase: the non-ideal gel filtration high performance liquid chromatography. Physico-chemical and immunochemical characteristics of the enzyme]. 318 26

Cystathionase activity has been demonstrated in human and rabbit lenses, using L-homoserine as substrate. The amount of activity found was quite low, 0.05 and 0.08 nmol of alpha-ketobutyrate formed/h/mg protein in human and rabbit lenses, respectively. The human lens cystathionase was found to have a pH maximum of 8.5 and a Km of 23.8 mM for L-homoserine. A sensitive assay, involving the use of high performance liquid chromatography, was developed to measure the small amounts of alpha-ketobutyrate produced.
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PMID:High performance liquid chromatography determination of cystathionase activity in human and rabbit lenses. 360 51

Cell lines established from donors with the inherited disorder ataxia-telangiectasia (A-T) exhibit exceptional sensitivity to ionizing radiation and chemicals known to produce increased levels of intracellular H2O2, suggesting a deficiency in glutathione-dependent detoxication reactions. Glutathione (GSH) biosynthesis in fibroblast and lymphoblast cultures derived from individuals known to be clinically unaffected, homozygous, or heterozygous for A-T was assessed. Following GSH depletion by diethylmaleate, fibroblasts (GM 3492) from a clinically unaffected individual resynthesized GSH at a rate approximately twice that observed in fibroblasts from known heterozygotes (GM 3488 and GM 3489). Unrelated A-T homozygote fibroblast lines GM 3487B and GM 5823 resynthesized GSH only very slowly. GM 3492 cells repleted intracellular GSH by 6 h after depletion, the heterozygote lines by 18 h. The A-T homozygotes replaced only 30% of the intracellular GSH pool by 24 h. A lymphoblast cell line from the A-T homozygote (GM 3189) also exhibited slow resynthesis after depletion. However, if these cells were permeabilized by treatment with digitonin, GSH synthesis proceeded at a rate exceeding synthesis in permeabilized or untreated normal lymphoblasts (GM 3323). The first enzyme in GSH synthesis, gamma-glutamylcysteine synthetase, was found to be elevated about 2.7-fold in A-T homozygote fibroblasts, suggesting that a substrate for GSH synthesis may be rate limiting. A-T homozygote lymphoblasts contained about 2-fold more gamma-cystathionase activity over other cell lines tested suggesting increased flux through the transsulfuration pathway for cysteine production in response to reduced cysteine supply. Transport of cysteine and cystine was found to be 8- and 5-fold slower in A-T homozygotes that did not affect fibroblasts while glutamate and methionine transport Vmax did not differ among the cell lines tested. These experiments demonstrate that cells from A-T homozygotes are deficient in cysteine transport, thus limiting GSH resynthesis after a depleting challenge such as radiation or GSH-depleting xenobiotic compounds.
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PMID:Imparied glutathione biosynthesis in cultured human ataxia-telangiectasia cells. 362 Nov 55

Cell growth using homocysteine as a source of cysteine-sulphur requires two enzymes, cystathionine synthase (CS) and gamma-cystathionase (CT). The second of these enzymes, CT, is apparently present in most cell lines regardless of their tissues of origin, since most cells can grow in vitro in the absence of cystine if they are provided with cystathionine, the intermediate in the pathway. Likewise, homocysteine will support the growth of many human cells. However, of a wide range of rodent cells, only well-differentiated rat hepatoma cells were found to grow using homocysteine in place of cystine. It is shown that cell growth in homocysteine-medium correlates well with the presence in the cells of detectable levels of CS. Furthermore, in cells able to grow in homocysteine-medium, it is possible to demonstrate the homocysteine-dependent trans-sulphuration of serine to cysteine. Growth in homocysteine-medium is not dependent on the release of preformed cysteine from disulphide complexes with serum proteins. In cell hybrids, and in 'dedifferentiated' variants of rat hepatomas, CS, but not CT, is subject to extinction coordinately with well-characterized liver-specific traits. For rodent cells, homocysteine-medium thus acts as a selective medium requiring the expression of a single liver-specific trait, CS. In addition it is shown that, in certain hepatoma variants, CS is regulated co-ordinately with a urea-cycle enzyme (carbamoyl phosphate synthetase I) by glucocorticoids and cyclic-AMP. Cell death through cysteine starvation is briefly considered. The immediate cause of death is apparently an insufficient supply of reduced glutathione. Selenium and vitamin E assist cell growth when the supply of cysteine is limiting.
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PMID:Characterization of cystathionine synthase as a selectable, liver-specific trait in rat hepatomas. 379 84

Rat liver gamma-cystathionase has been purified to homogeneity (verified by SDS electrophoresis and ultracentrifugation). The secondary and tertiary structures of the enzyme were studied by circular dichroism spectra. Our studies revealed that the holoenzyme molecule comprises approximately 22% of alpha-helices, 14% of beta-structure, 14% of beta-bends, and 50% of unordered structure. Conformational alterations of the enzyme molecule resulting from enzyme PLP elimination, reduction with sodium borohydride and irreversible inhibition by propargylglycine were examined. The enzyme's secondary structure was shown to be stable whereas the tertiary structure is labile. Saturation with PLP maintains the enzyme's optimal (catalytically active) tridimensional structure. Sodium dodecylsulfate alters its secondary (the amount of alpha-helix being raised to 34%) and tertiary structures.
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PMID:[Purification of homogeneous gamma-cystathionase and study of its structure by circular dichroism]. 398 10

Rat liver homogenates heated for 10 min at 60 degrees C incubated with L-cystathionine yield cystathionine ketimine which was identified by its typical UV spectrum and by cochromatography with authentic samples on the amino acid analyzer. Alanine and alpha-amino butyric acid have been also detected among the final products. The reaction is due to heat stable gamma-cystathionase and transaminases present in the extracts. Cystathionase produces alpha-keto butyric acid and pyruvic acid which are then used for the transamination of the remaining cystathionine to yield the ketimine. This is the first report indicating the occurrence in a mammalian tissue of an enzymatic system using cystathionine for reactions differing from the traditional transulfuration to cysteine.
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PMID:The conversion of L-cystathionine into the cyclic ketimine form by heated rat liver extracts containing cystathionase and transaminase activities. 402 71

Alloxan-induced diabetes results in changes in the activities of a number of enzymes related to methyl group metabolism in sheep. Decreases in the activities of phospholipid methyltransferase and betaine-homocysteine methyltransferase in diabetic sheep liver indicate a reduced rate of choline synthesis and oxidation. A 65-fold increase in the activity of glycine methyltransferase and a 4-fold rise in the activity of gamma-cystathionase in diabetic sheep liver with elevated urinary excretion of cyst(e)ine suggest that catabolism of the methyl group of methionine and homocysteine was enhanced in the diabetic state.
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PMID:Disturbance of methyl group metabolism in alloxan-diabetic sheep. 403 11


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