Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

The prostaglandin D synthetase system was isolated from rat brain. Prostaglandin endoperoxide synthetase solubilized from a microsomal fraction catalyzed the conversion of arachidonic acid to prostaglandin H2 in the presence of heme and tryptophan. Prostaglandin D synthetase (prostaglandin endoperoxidase-D isomerase) catalyzing the isomerization of prostaglandin H2 to prostaglandin D2 was found predominantly in a cytosol fraction and was purified to apparent homogeneity with a specific activity of 1.7 mumol/min/mg of protein at 24 degrees C. The enzyme also acted upon prostaglandin G2 and produced a compound presumed to be 15-hydroperoxy-prostaglandin D2. Glutathione was not required for the enzyme reaction, but the enzyme was stabilized by thiol compounds including glutathione. The enzyme was inhibited by p-chloromercuribenzoic acid in a reversible manner. The purified enzyme was essentially free of the glutathione S-transferase activity which was found in the cytosol of brain.
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PMID:Purification and properties of prostaglandin D synthetase from rat brain. 10 31

The carcinogen 4-nitroquinoline 1-oxide (4-NQO) was found to rapidly deplete non-protein thiols (NPSH) from Ehrlich ascites tumor cells and V79 Chinese hamster fibroblasts. The effects of NPSH on 4-NQO metabolism were studied by measuring 4-hydroxyaminoquinoline 1-oxide formation, CN- -insensitive oxygen consumption, and reduction of ferricytochromes c + c1 in normal cells and in cells pretreated with the thiol reagent N-ethylmaleimide. Removal of thiols before treatment with 4-NQO resulted in increased production of 4-hydroxyaminoquinoline 1-oxide and increased production of nitro radicals. The NPSH thus appeared to play a significant role in 4-NQO detoxification. Glutathione, when present in culture medium during 4-NQO treatment, protected V79 cells from 4-NQO toxicity. Several mechanisms for reaction of 4-NQO with intracellular NPSH were indicated. Both V79 and Ehrlich cells contained appreciable amounts of glutathione S-transferase (EC 2.5.1.18), which catalyzes the nucleophilic substitution of the nitro group of 4-NQO with thiols. Greater thiol loss under oxic than under hypoxic conditions suggested oxidation by superoxide, peroxide, or hydroxyl radical formed in the course of 4-NQO reduction. In addition, reaction of thiols with nitro radicals or with nitrosoquinoline 1-oxide was indicated by the inhibitory effect of glutathione on oxygen consumption in solutions of 4-NQO and sodium ascorbate.
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PMID:Interactions of the carcinogen 4-nitroquinoline 1-oxide with the non-protein thiols of mammalian cells. 11 Apr 43

Glutathione derivatives inhibit glutathione S-transferase A [cf. Biochem. J. (1975) 147, 513--522]. The steady-state kinetics of this inhibition have been investigated in detail by using S-octyglutathione, glutathione disulphide and S-(2-chloro-4-nitrophenyl)glutathione: the last compound is a product of the enzyme-catalused reaction. Interpreted in terms of generalized denotations of inhibition patterns, the compounds were found to be competitive with the substrate glutathione. Double-inhibition experiments involving simultaneous use of two inhibitors indicated exclusive binding of the inhibitors to the enzyme. The discrimination between alternative rate equations has been based on the results of weighted non-linear regression analysis. The experimental error was determined by replicate measurements and was found to increase with velocity. The established error structure was used as a basis for weighting in the regression and to construct confidence levels for the judgement of goodness-of-fit of rate equations fitted to experimental data. The results obtained support a steady-state random model for the mechanism of action of glutathione S-transferase A and exclude a number of simple kinetic models.
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PMID:Multiple inhibition of glutathione S-transferase A from rat liver by glutathione derivatives: kinetic analysis supporting a steady-state random sequential mechanism. 44 9

The binding of substrates and a product to glutathione S-transferase A from rat liver was studied by use of equilibrium dialysis and equilibrium partition in a two-phase system. The radioactive substrates glutathione and bromosulfophthalein as well as a product of glutathione and 3,4-dichloro-1-nitrobenzene, S-(2-chloro-4-nitrophenyl)glutathione, gave hyperbolic binding isotherms with a stoichiometry of 2 mol per mol of enzyme (i.e. 1 molecule per subunit). Glutathione (and glutathione disulfide) had an equilibrium (dissociation) constant for the binding of about 10 microM, whereas bromosulfophthalein and the product had equilibrium constants of about 0.5 microM. All ligands showed the same binding stoichiometry, and competition experiments involving unlabeled ligands indicated that glutathione and the glutathione derivatives were binding to the same site. Low affinity sites appeared to exist in addition to the specific high affinity sites (one per subunit) for all ligands tested. The binding studies are fully consistent with a steady state random kinetic mechanism for the enzyme.
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PMID:The binding of substrates and a product of the enzymatic reaction to glutathione S-transferase A. 45 71

Rats and mice were exposed to the fumes of oxidative thermal degradation of polystyrene (350 degrees C). A decrease in the reduced glutathione (GSH) in both liver and lung was detected immediately after both the acute (mice, 3 h) and subacute (rats, 3 weeks) exposures were stopped. Later on an elevation in the amount of GSH due to the increased synthesis (rebound effect) could be seen. Cytochrome P-450 content in mouse liver was initially decreased after acute exposure, but the prolonged treatment doubled the amount of the P-450 hemoprotein in liver microsomes. After acute exposure 7-ethoxycoumarin 9-deethylase activity in mouse liver was doubled in 24 h. When the exposures were continued, this enhancement in ethoxycoumarin O-deethylase activity gradually disappeared. O-deethylase activity was also enhanced in rat liver and lung after subacute exposure. The exposures given had no effect on diphenyloxazole hydroxylase, and the effects on the conjugating enzymes (epoxide hydratase, UDPglucuronosyltransferase, glutathione S-transferase)) were insignificant in rat liver.
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PMID:Effects of thermal degradation products of polystyrene on drug biotransformation and tissue glutathione in rat and mouse. 73 18

Two forms of glutathione S-aryltransferase were purified from rat liver. The only differences noted between the two forms were in the chromatographic and electrophoretic properties, which permitted the separation of the two species. The molecular weights of the enzyme and its subunits were estimated as about 50000 and 23000 respectively. The steady-state kinetics did no follow Michaelis-Menten kinetics when one substrate concentration was kept constant while the second substrate concentration was varied. Several S-substituted GSH derivatives were tested as inhibitors of the enzymic reaction. The enzyme was inactivated by thiol-group reagents.
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PMID:Purification and characterization of two glutathione S-aryltransferase activities from rat liver. 81 Jan 39

The catalyzed reactions of GSH with organic nitrate and thiocyanate esters and with a series of chloronitrobenzene substrates have been investigated and the results used to formulate a mechanism for glutathione S-transferase catalysis. All the homogeneous preparations of the glutathione transferases that have been tested catalyze the reaction of GSH with organic nitrates and thiocyanates. The nature of the reaction with nitrate esters, resulting in the formation of GSSG rather than a thioether, has been investigated further. The presence of an additional nonsubstrate thiol decreased the formation of GSSG to an extent that cannot be explained by disulfide interchange. These results are interpreted to reflect the enzymatic formation of an unstable glutathione sulfenyl nitrite that undergoes subsequent non-enzymatic decomposition. Hammett plots of the catalytic constants of rat liver transferases B and C obtained with a series of 4-substituted 1-chloro-2-nitrobenzene substrates demonstrate a linear relationship with sigma- substituent constants, reflecting the nucleophilic nature of the enzymatic reactions and their strong dependence on the electrophilicity of the nonthiol substrate. These data suggest that the many diverse reactions catalyzed by the glutathione transferases may be formulated as a nucleophilic attack of enzyme-bound GSH on the electrophilic center of the second substrate. The final products observed reflect this primary event and the existence of subsequent nonenzymatic reactions.
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PMID:Mechanism for the several activities of the glutathione S-transferases. 97 64

Ligandin (Y protein) is an abundant cytoplasmic glutathione transferase present in liver, kidney and gut in various animals and man. Its interaction with four radiologic contrast media (Telepaque, 3-(3 amino-2,4,6, triiodophenyl -2 ethylpropanoic acid, sodium salt; Hypaque, sodium -3, 5-diacetamido-2,4,6,-triiodobenzoate; Cholografin, N,N'adipyl-bis-(3-amino-2,4,6-triiodobenzoic acid) N-methyl-glucosamine; Diodrast, 3,5-Diiodo-4-pyridone-N-acetic acid, Diethanolamine Salt was investigated by observing inhibitory effects on the enzyme-catalyzed conjugation of glutathione with 1-chloro-2, 4-dinitrobenzene. Lineweaver-Burk plots of reciprocal initial velocity versus reciprocal inhibitor concentrations at fixed glutathione and chlorodinitrobenzene concentrations demonstrate non-competitive inhibition by all contrast media except Diodrast. No conjugates of contrast media with glutathione were formed. It is postulated that intracellular accumulation of contrast media is aided by intracellular binding with ligandin. Inhibition of the GSH transferase activity of ligandin can disrupt the mercapturate formation, an important detoxification process.
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PMID:Interaction of ligandin with radiographic contrast media. 100 14

Serum albumins of certain animal species (cow, sheep, pig) accelerate the decomposition of prostaglandin endoperoxides, with formation of large amounts of prostaglandin D. The reaction is inhibited by arachidonic acid, which suggests an interaction of the endoperoxide with the fatty acid binding sites of serum albumin. Glutathione-S-transferases, in the presence of glutathione, convert the endoperoxide into a mixture of prostaglandin F2alpha, E2 and D2. The prostaglandin D/E-ratio depends on the transferase used. The known rat liver transferases give mainly prostaglandin F2alpha and E2, but a new transferase in sheep lung was discovered which gives rise to large quantities of prostaglandin F2alpha and D2. The sheep lung transferase was purified to homogeneity. Two iso-enzymes with identical enzymic activity were obtained. The major component (transferase SL 2, an iso-enzyme of glutathione-S-transferase, EC 2.5.1.18) has a molecular weight of 45 000 and consists of two subunits. Its isoelectric point is 9,8-9.9. These properties, as well as the amino acid composition and the substrate specificity for typical transferase substrates, indicate a close resemblance to transferase B (ligandin), a major binding protein of rat liver. Although purified glutathione peroxidase from erythrocytes is very active in catalysing the reduction of the 15-hydroperoxy group of prostaglandins, it does not have any effect on the decomposition of the endoperoxide group.
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PMID:Conversions of prostaglandin endoperoxides by glutathione-S-transferases and serum albumins. 100 99

The oncosuppressive effect of melatonin on 9,10-dimethyl-1,2-benzanthracene (DMBA) induced rat mammary tumorigenesis led us to assess its possible modulatory influence on representative hepatic and mammary drug metabolizing enzymes in DMBA treated female Holtzman rats, reared in short and long photoperiods. Melatonin treated rats in either photoperiod showed a significant induction in hepatic and mammary levels of glutathione (GSH) and cytosolic activities of glutathione S-transferase (GST) when compared with the corresponding controls, along with a significant drop in hepatic microsomal contents of cytochromes b5 and P450. This induction of GSH and GST, and depletion of cytochromes b5 and P450 by melatonin may possibly be related to its anticarcinogenic potential in this tumor model.
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PMID:A possible modulatory influence of melatonin on representative phase I and II drug metabolizing enzymes in 9,10-dimethyl-1,2-benzanthracene induced rat mammary tumorigenesis. 128 33


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