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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Recent studies have shown that endrin induces lipid peroxidation and may produce toxicity through an oxidative stress. We have therefore examined the effect of endrin administration to rats on glutathione content and the activities of glutathione metabolizing enzymes. 2. The oral administration of endrin resulted in dose- and time-dependent decreases in hepatic and renal glutathione content with maximum depletion (90%) occurring in liver at approximately 24 hr post-treatment. 3. Decreases in glutathione content were also observed in lung, brain, spleen and heart. 4. Endrin (4 mg/kg) decreased selenium dependent glutathione peroxidase activity in liver and kidney by 64 and 50%, respectively, while small increases were observed in the activities of glutathione reductase and glutathione S-transferase. 5. The toxicity of endrin may be at least in part related to oxidative tissue damage associated with depletion of glutathione and inhibition of glutathione peroxidase activity.
Gen Pharmacol 1990
PMID:Endrin-induced depletion of glutathione and inhibition of glutathione peroxidase activity in rats. 227 83

The GSH-binding site of glutathione S-transferase (GST) isoenzymes was studied by investigating their substrate-specificity for three series of GSH analogues; further, a model of the interactions of GSH with the G-site is proposed. Twelve glycyl-modified GSH analogues, four ester derivatives of GSH and three cysteinyl-modified GSH analogues were synthesized and tested with purified forms of rat liver GST (1-1, 2-2, 3-3 and 4-4). The glycyl analogues exhibited spontaneous chemical reaction rates with 1-chloro-2,4-dinitrobenzene comparable with the GSH rate. In contrast, the enzymic rates (Vmax.) differed greatly, from less than 1 up to 140 mumol/min per mg; apparently, a reaction mechanism is followed that is very sensitive to substitutions at the glycyl domain. No correlation exists between the chemical rates and Vmax. values for the analogues. Analogues of GSH in which L-cysteine was replaced by D-cysteine, L-homocysteine or L-penicillamine showed little or no capacity to replace GSH as co-substrate for the GSTs. GSH monomethyl and monoethyl esters showed Vmax. values greater than the Vmax. measured with GSH: the Vmax. for the monoethyl ester of GSH and GST 3-3 was 5-fold that for GSH. The data obtained in this and previous studies [Adang, Brussee, Meyer, Coles, Ketterer, van der Gen & Mulder (1988) Biochem. J. 255, 721-724; Adang, Meyer, Brussee, van der Gen, Ketterer & Mulder (1989) Biochem. J. 264, 759-764] allow a model of the interactions of GSH in the G-site in GSTs to be postulated. The gamma-glutamyl site is the main binding determinant: the alpha-carboxylate group is obligatory, whereas shifting of the amino group and shortening of the peptide backbone only decreased kcat./Km. Furthermore, the GSTs appear to be very critical with respect to a correct orientation of the thiol group of the GSH analogue. The glycyl site is the least restrictive domain in the G-site of GSTs: amino acid analogues all showed Km values between 0.2 and 0.6 mM (that for GSH is 0.2-0.3 mM), but large differences in Vmax. exist. The glycyl carboxylate group is not essential for substrate recognition, since decarboxy analogues and ester derivatives showed high activities. The possible mechanisms for an increased Vmax. in some analogues are briefly discussed.
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PMID:The glutathione-binding site in glutathione S-transferases. Investigation of the cysteinyl, glycyl and gamma-glutamyl domains. 237 57

The presence of glutathione transferase (GST; EC 2.5.1.18) in Escherichia coli ATCC 25922, E. coli ATCC 25422, Proteus vulgaris ATCC 8427, Pseudomonas aeruginosa ATCC 27853, Klebsiella oxytoca CIP 666, K. oxytoca AF 101, Enterobacter cloacae CIP 6085, Serratia marcescens CIP 6755, and Proteus mirabilis AF 2924 was investigated. Using 1-chloro-2,4-dinitrobenzene as substrate, GST activity was found in the glutathione-(GSH-)affinity-purified fraction of all strains tested. SDS-PAGE analysis of GSH-affinity-purified enzyme indicated that the GSTs of all these bacteria are dimers of two identical subunits of Mr about 22,500. Rabbit antiserum directed against the major isoenzyme present in Proteus mirabilis AF 2924, Pm-GST-6.0, was used to investigate the antigenic properties of bacterial GSTs. Western blot analysis indicated that a GST antigenically identical to Pm-GST-6.0 is present in Enterobacter cloacae CIP 6085, Escherichia coli ATCC 25422 and Proteus vulgaris ATCC 8427, but absent in Escherichia coli ATCC 25922, Klebsiella oxytoca CIP 666, K. oxytoca AF 101 and Serratia marcescens CIP 6755. The presence of Pm-GST-6.0, but not mammalian GST, increased the MIC values of amikacin, ampicillin, cefotaxime, cephalothin and nalidixic acid for E. coli ATCC 25922. It is suggested that bacterial GST may represent a defense against the effects of antibiotics.
J Gen Microbiol 1989 Nov
PMID:Glutathione transferase in bacteria: subunit composition and antigenic characterization. 261 80

Analogues of GSH in which either the gamma-glutamyl or the glycyl moiety is modified were synthesized and tested as both substrates for and inhibitors of glutathione S-transferases (GSTs) 7-7 and 8-8. Acceptor substrates for GST 7-7 were 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid (ETA) and for GST 8-8 CDNB, ETA and 4-hydroxynon-trans-2-enal (HNE). The relative ability of each combination of enzyme and GSH analogue to catalyse the conjugation of all acceptor substrates was similar with the exception of the combination of GST 7-7 and gamma-L-Glu-L-Cys-L-Asp, which used CDNB but not ETA as acceptor substrate. In general, GST 7-7 was better than GST 8-8 in utilizing these analogues as substrates, and glycyl analogues were better than gamma-glutamyl analogues as both substrates and inhibitors. These results are compared with those obtained earlier with GSH analogues and GST isoenzymes 1-1, 2-2, 3-3 and 4-4 [Adang, Brussee, Meyer, Coles, Ketterer, van der Gen & Mulder (1988) Biochem. J. 255, 721-724] and the implications with respect to the nature of their active sites are discussed.
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PMID:Interaction of rat glutathione S-transferases 7-7 and 8-8 with gamma-glutamyl- or glycyl-modified glutathione analogues. 261 14

Glutathione peroxidases, glutathione transferase, glutathione reductase and gamma-glutamyl transpeptidase activities were analyzed in human thyroid tissues obtained from 17 patients undergoing resectional surgery because of a malignancy. It was deduced, from measurements of glutathione peroxidase activity with both H202 and cumene hydroperoxide, that thyroid contains only the selenium enzyme. The absence of selenium independent glutathione peroxidase activity in thyroid was confirmed with gel filtration experiments. An interindividual variation of about 28-fold was found measuring glutathione transferase activity with 1-chloro-2,4-dinitrobenzene. Subjecting a fraction of human thyroid cytosols partially purified by G-100 Sephadex column to isoelectricfocusing run, a single peak of glutathione transferase activity centered at pH 4.6 was obtained. An adequate level of glutathione reductase and gamma-glutamyl transpeptidase activities was also found in all specimens investigated.
Gen Pharmacol 1987
PMID:Glutathione metabolizing enzyme activities in human thyroid. 288 74

A series of GSH analogues with modifications at the gamma-glutamyl moiety was synthesized and purified by following peptide chemistry methodology. Benzyl, benzyloxycarbonyl and t-butyloxycarbonyl protective groups were used to protect individual amino acid functional groups. The formation of peptide bonds was accomplished through coupling of free amino groups with active esters, generated by reaction of the carboxylate functions with dicyclohexylcarbodi-imide and 1-hydroxybenzotriazole. The protecting groups in the tripeptides were removed in a single step by using Na in liquid NH3. Precautions were taken in order to prevent oxidation of the thiol function in the cysteine residue. Thus GSH analogues containing both L- and D-glutamic acid and L- and D-aspartic acid, coupled to cysteinylglycine through both the alpha- and the omega-carboxylate group, were synthesized. Also, decarboxy-GSH and deamino-GSH, lacking one functional group in the glutamate moiety, were prepared. The spontaneous non-enzyme-catalysed nucleophilic reaction of these GSH analogues with the electrophilic model substrate 1-chloro-2,4-dinitrobenzene showed appreciable rate differences, indicating the importance of intramolecular interactions in determining the nucleophilic reactivity of the thiol function in the cysteine residue. In particular, the free amino group in the gamma-L-glutamic acid residue appears to play a crucial role in activating the thiol group in GSH. In an adjacent paper [Adang, Brussee, Meyer, Coles, Ketterer, van der Gen & Mulder (1988) Biochem. J. 255, 721-724] these results are compared with those obtained in a study on the ability of these GSH analogues to act as a co-substrate in the glutathione S-transferase-catalysed conjugation reaction with 1-chloro-2,4-dinitrobenzene.
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PMID:Synthesis and nucleophilic reactivity of a series of glutathione analogues, modified at the gamma-glutamyl moiety. 290 8

Changes in reduced glutathione levels in liver, lung and whole blood of female Swiss-Webster mice with age were determined. In addition, glutathione content, and glutathione S-transferase and glutathione reductase activities of erythrocytes and lymphocytes of mice as a function of age were examined. Reduced glutathione content increased in liver, lung, whole blood, erythrocytes and lymphocytes with age from 3 to 9 months, reached a maximum level at 9 months of age and decreased thereafter with advanced age in all tissues. Glutathione S-transferase and glutathione reductase activities in erythrocytes and lymphocytes increased with age from 3 to 9 months, reached maximum activities at 9 months and decreased thereafter with advanced age. The glutathione content of erythrocytes from animals 18 months of age decreased by 56% as compared to 9 month old mice, while the activities of glutathione S-transferase and glutathione reductase decreased by 56 and 48%, respectively, over the same age span.
Gen Pharmacol 1984
PMID:Changes in glutathione and glutathione metabolizing enzymes in erythrocytes and lymphocytes of mice as a function of age. 673 42

1. Specific activities of glutathione S-transferase towards four model substrates were determined in guinea-pig brain 50,000 g supernatant and compared with those obtained for liver and kidney extract. 2. By using 1-chloro-2,4-dinitrobenzene as substrate, glutathione S-transferase activity was measured in different anatomical regions of brain; cerebellum expressed the highest conjugating capacity. 3. Brain glutathione S-transferase was resolved into four major peaks (PI 6.10, 6.60, 7.15, 7.65) each having similar kinetic constants for both substrates GSH and 1-chloro-2,4-dinitrobenzene. 4. Likewise, four forms, focused at pH 6.45, 7.14, 7.50 and 8.88, were obtained from liver. 5. Unlike hepatic tissue, brain does not possess the highly alkaline form which displays Se-independent GSH peroxidase activity. 6. Several psychotropic agents, including chlorpromazine and chlorazepate, produced a considerable in vitro inhibition on brain transferase activity.
Gen Pharmacol 1982
PMID:Glutathione S-transferase activity from guinea-pig brain: a comparison with hepatic multiple forms. 681 96

1. Changes in the activity of glutathione S-transferase (GST) in liver, lungs and intestinal mucosa of female Swiss-Webster mice with age were determined. 2. GST activity increased with age from 1 to 9 months, reached a maximum activity at 9 months and decreased thereafter with advanced age in all three tissues. 3. GST activity decreased by approximately 75% in liver between 9 and 18 months, with decreases of 65 and 64% occurring over the same time period for lung and intestinal mucosa, respectively.
Gen Pharmacol 1982
PMID:Glutathione S-transferase activity in liver, lung and intestinal mucosa of aging female mice. 715 32

Maize glutathione S-transferase (GST) isozymes are encoded by a gene family comprising at least five genes, three of which (Gst I, II and III) have recently been isolated and sequenced. The enzymes are active as homo or heterodimers and exhibit intraspecific polymorphism including a "null" variant for the two major isoforms expressed in roots. Northern blot analyses performed on total root RNA from "null" and "plus" genotypes, using Gst I- and Gst II-specific probes, indicated that the Gst I gene controls the expression of the two major GST isoforms expressed in roots. Gst I and Gst II were mapped by RFLP analysis using an F2 population of 149 individuals previously characterized. Gst I was localized on the long arm of chromosome 8, while two putative Gst II loci were mapped to chromosome 8 (70 cM from Gst I) and 10, respectively.
Mol Gen Genet 1995 Sep 20
PMID:Molecular analysis and mapping of two genes encoding maize glutathione S-transferases (GST I and GST II). 747 52


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