Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.47 (cysteine synthase)
 625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The maximum activities of the enzymes for the biosynthesis of GSH (gamma-glutamyl-cysteine synthetase and GSH synthetase) have been assayed in high GSH and low GSH erythrocytes from Tasmanian Merino and Finnish Landrace sheep. 2. For the Merinos, the activities (mumol product/g haemoglobin per min +/- S.E.M. (n)) in the high and low GSH erythrocytes respectively were: gamma-glutamyl-cysteine synthetase: 0.776 +/- 0.065 (11) and 0.375 +/- 0.063 (13); and GSH synthetase: 0.069 +/- 0.003 (11) and 0.066 +/- 0.002 (13). 3. For the Finnish Landrace sheep the activities in the high and low GSH erythrocytes respectively were: gamma-glutamyl-cysteine synthetase: 0.595 +/- 0.063 (12) and 0.555 +/- 0.033 (10) and gamma-glutamyl-cysteine synthetase: 0.073 +/- 0.002 (12) and 0.070 +/- 0.002 (10). 4. gamma-Glutamyl-cysteine synthetase was markedly inhibited by physiological GSH concentrations. No evidence was found for the presence of an inhibitor of GSH biosynthesis (other than GSH) in low GSH erythrocytes from Finnish Landrace sheep. 5. Although for the Merinos the low GSH trait can be explained in terms of a diminished activity of gamma-glutamyl-cysteine synthetase, no such explanation is tenable for the Finnish Landrace sheep.
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PMID:GSH biosynthesis in glutathione deficient erythrocytes from Finnish landrace and Tasmanian merino sheep. 117 55

59FeCl3 was used to measure red cell life span in GSH-low type sheep to the Tasmanian Merino breed, whose GSH deficiency is due to a diminished activity of gamma-glutamyl cysteine synthetase. The 59Fe survival slopes fell within normal limits, indicating that red cells with this type of GSH deficiency do not have a shortened life span.
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PMID:The life span of glutathione-deficient red cells in Tasmanian Merino sheep. 121 91

This study was carried out to investigate the mechanism of Rifampicin (RIF) induced glutathione (GSH) depletion in M. smegmatis. RIF at various concentrations decreased the activities of gamma glutamyl cysteine synthetase (GGCS) and GSH synthetase. Maximum decrease in the activities of biosynthetic enzymes of GSH was observed when 15 micrograms RIF ml-1 medium was incorporated in the growth medium before performing inoculations. The activity of GGCS was also decreased when three day grown M. smegmatis was exposed to 60 micrograms RIF ml-1 medium for a period of 6 h and 9 h. RIF did not alter the activity of gamma glutamyl transferase. The results of the present study demonstrate that the depletion caused by RIF in cellular GSH is due to its decreased biosynthesis whereas its degradation is not affected in M. smegmatis.
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PMID:Inhibition of cellular glutathione biosynthesis by rifampicin in Mycobacterium smegmatis. 135 83

Platinum-based chemotherapy has led to an improvement in complete response rates and duration of median remission, but has only given a modest improvement in overall survival in patients with advanced ovarian cancer. Chemotherapy will in the future focus upon: (1) improving the complete remission rate with new induction regimens; (2) identifying strategies capable of converting partial remission into complete remission; (3) preventing or delaying recurrences in patients who do achieve a complete remission; (4) identifying mechanisms of antineoplastic drug resistance and pharmacologic techniques capable of reversing drug resistance. Among the treatment approaches being utilized are high-dose chemotherapy with autologous bone marrow transplantation, development of new chemotherapeutic regimens which include Taxol and hexamethylmelamine, and intraperitoneal chemotherapy. In addition, our understanding of the mechanisms of antineoplastic drug resistance has led to the development of novel therapeutic approaches. It has been demonstrated that resistance to platinum and alkylating agents is associated with both increased concentrations of cellular glutathione (GSH) as well as an increased capacity of tumor cells to repair damage to DNA. Inhibition of GSH biosynthesis with buthionine sulfoximine (BSO), a synthetic inhibitor of the enzyme gamma glutamyl cysteine synthetase, has led to the potentiation of alkylating agent activity in vitro and in vivo. A phase I trial of BSO plus melphalan is currently in progress and a trial of BSO plus carboplatin is planned. Inhibition of the DNA repair process with aphidicolin potentiates the cytotoxicity of cisplatin in drug-resistant tumor cells. Clinical trials of aphidicolin plus cisplatin await the completion of ongoing phase I trials of aphidicolin.
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PMID:Role of chemotherapy in the future treatment of ovarian cancer. 135 5

The effect of dietary polyunsaturated fatty acids (PIFA) upon the content of reduced glutathione (GSH) of the kidney was studied in 32 male Wistar rats. Two equal size groups were fed diets supplemented with either 10% or 18% corn oil. Sixteen hours before death, half of each experimental group was submitted to fasting. The content of GSH and the activity of gamma glutamyl transpeptidase (GGTP) and gamma glutamyl cysteine synthetase was determined in kidney tissue. Fasting led to a reduction of GSH from 3.21 +/- 0.54 to 1.25 +/- 0.20 mumol per gm in the group fed 10%. PIFA. Equivalent figures for the group fed 18% PIFA were 3.49 +/- 0.54 and 0.49 +/- 0.08, respectively. GGTP activity increased significantly after fasting but no differences were observed according to level of PIFA intake. The exaggerated reduction of GSH during fasting after a high PIFA intake may expose the animals to risk of cell damage induced by peroxides or other oxidating agents.
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PMID:[Effect of dietary polyunsaturated fatty acids on the content and metabolism of glutathione in rat kidney]. 136 17

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

The present studies demonstrate that the ability of supplemental selenite to alter the in vitro growth of canine mammary tumor cell line 13 was dependent on the quantity and duration of selenium exposure and on the culture density. Exposure to 3.2 microM selenite did not significantly alter growth but led to an increase in intracellular glutathione (GSH). The severity of growth inhibition between 3.2 and 9.6 microM selenite was dependent on the duration of exposure and culture density. The toxicity of selenite generally increased as the culture density increased. Likewise, changes in intracellular GSH were dependent on the quantity and duration of selenite exposure and the culture density. Depressing intracellular GSH by increasing the culture density or by incubating with buthionine sulfoximine; a specific inhibitor of gamma-glutamyl cysteine synthetase, increased the severity of growth inhibition caused by selenite and markedly increased cellular retention of selenium. Nevertheless, marked cellular retention of selenium did not occur until growth was inhibited by more than 50%. The present studies revealed that the log of the molar ratio of GSH to selenium correlated negatively with the severity of growth inhibition (P less than 0.0001). These studies suggest that cellular toxicity of selenite is dependent on the regulation of the GSH:selenium ratio. An inability to regulate this ratio likely leads to the accumulation of toxic seleno compounds.
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PMID:Influence of intracellular glutathione on selenite-mediated growth inhibition of canine mammary tumor cells. 173 67

Gastric mucous epithelial cells may represent a first line of defense against reactive oxygen species that are generated within the gastric lumen. However, little is known about their defenses against oxidant species. This study examined the importance of the glutathione (GSH) redox cycle and of endogenous catalase as antioxidant defenses in cultured gastric mucous cells. Cultured rat gastric mucous cells were exposed to H2O2 generated by glucose oxidase acting on glucose or to nascent H2O2 for 5 h. Cytotoxicity was quantified by measuring 51Cr release from prelabeled cells. The effects of inhibition of the GSH redox cycle and of endogenous catalase were examined. Glucose oxidase caused a dose-dependent increase of 51Cr release. Similarly, nascent H2O2 damaged the cells dose dependently. Pretreatment with 1,3-bis(chloroethyl)-1-nitrourea (inhibitor of GSH reductase) dose dependently increased glucose oxidase-induced 51Cr release. Preincubation with buthionine sulfoximine (inhibitor of gamma-glutamyl-cysteine synthetase), which lowered intracellular GSH content, enhanced glucose oxidase-induced damage in a dose-dependent manner. Pretreatment with diethyl maleate, which covalently binds GSH as catalyzed by GSH transferase, also enhanced the sensitivity to lysis by glucose oxidase. However, inhibition of endogenous catalase activity by 3-amino-1,2,4-triazole did not significantly alter glucose oxidase- or nascent H2O2-induced 51Cr release. These results suggest that the GSH redox cycle rather than endogenous catalase plays a critical role in intracellular antioxidant defense in cultured gastric mucous cells.
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PMID:Antioxidant defenses of cultured gastric cells against oxygen metabolites: role of GSH redox cycle and endogenous catalase. 176 53

Glutathione (GSH) and GSH-related enzymes, glutathione reductase (GR), gamma-glutamyl cysteine synthetase (gamma-GCS), gamma-glutamyl transpeptidase (gamma-GTP), glutathione S-transferase (GST) and adenosine triphosphatase (ATPase) enzymes were analysed to study the effect of busulfan on the defence mechanisms of the lens. All these enzymes were found to increase significantly except GSH which showed only 7.9% increase as compared to controls in precataractous stage. These results affirm that busulfan is capable of evoking a response from the enzymes involved in the various pathways of GSH enabling the lens to prolong its clarity. The cataractous lenses showed significant decrease in all these parameters. Here, the impairment of the defense mechanism (GST, GR) and the total ATPase may be attributed to the cumulative action of the drug which can react with -SH groups of these enzymes, ultimately causing opacification.
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PMID:Glutathione and glutathione-related enzymes in busulfan treated rat lens. 191 43

A number of enzyme systems are important in the protection of cells from chemical-induced oxidative damage. Little is known of the relative importance of these enzymes during postnatal development and its is possible that changes in their activity during this period may alter the susceptibility to toxic agents. This study investigated the activities of glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase, gamma-glutamyl-cysteine synthetase and glutathione synthetase in the liver, lung and kidney of postnatal and adult mice. The first 3 postnatal weeks are characterized by marked changes in the activities of enzymes that protect against oxidative stress (glutathione peroxidase/reductase, catalase and superoxide dismutase). Overall, the activity of these enzymes suggests that the mouse has a higher level of protection against peroxides at various stages during this period but lower capacity to detoxify superoxide anions. The activities of the glutathione-synthetic enzymes (gamma-glutamylcysteine synthetase and glutathione synthetase) were significantly lower in the kidney of the postnatal mice, but the liver and lung had levels similar to those in the adult. Glutathione turnover in the liver of 2-week-old mice was not different from that in adults. The results indicate a complex pattern of development in the activities of detoxification enzyme systems during postnatal development.
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PMID:Postnatal development of enzyme activities associated with protection against oxidative stress in the mouse. 196 50


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