Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have measured the activities of epoxide hydrase in microsomes and glutathione S-epoxidetransferase and glutathione S-aryltransferase in cytosol fractions of liver, lungs, kidneys, and small intestine from fetal and neonatal guinea pigs and rabbits. The rates at which adult values of these enzyme activities are reached in extrahepatic tissues differ from the rates of maturation of the hepatic enzyme activities for both species. In addition, the two pathways of epoxide metabolism studied here developed with age at different rates in any one organ. However, both cytosol glutathione S-transferases showed very similar developmental profiles in any one organ. It was especially interesting that the activities of both glutathione S-transferases were within the adult range in pulmonary cytosol fraction of guinea pig and rabbit before birth. Intestinal microsomes did not have adult values for epoxide hydrase activity until several weeks after birth. A feature common to both epoxide-metabolizing activities in hepatic and extrahepatic organs was a drop in mean specific activity, sometimes not statistically significant, around the time of birth. This decrease appeared to be due to dilution of the active enzyme with other protein, inasmuch as the total organ activity, in general, showed no such decline. We found that the pattern of development of hepatic microsomal epoxide hydrase activity was similar to developmental patterns published by others for hepatic microsomal mixed-function oxidases, and also that development of hepatic cytosol glutathione S-transferase was similar to hepatic development of glutathione S-transferase towards other substrates described in the literature.
 ...
PMID:The perinatal development of epoxide-metabolizing enzyme activities in liver and extrahepatic organs of guinea pig and rabbit. 1 72

In vitro drug metabolism in the Hartley guinea pig was compared with that in two inbred guinea pig strains used as carriers for the line 10 hepatoma. We observed minor differences in enzyme specific activity among the three strains. Three weeks after intradermal inoculation of Strain 2 guinea pigs with line 10 hepatoma cells, cytochrome P450 levels and aminopyrine demethylase activity were significantly decreased. Seven to 10 days after inoculation with the ascites form of the tumor, the activities of aniline and biphenyl hydroxylases, p-aminobenzoic acid N-acetyltransferase, and dichloronitrobenzene glutathione S-aryltransferase, in addition to those of cytochrome P450 and aminopyrine N-demethylase, were probably also described.
 ...
PMID:Effect of strain differences and tumor presence on microsomal drug metabolism in the guinea pig: brief communication. 20 Jul 61

Comparative studies of in vitro drug metabolism by hepatic and extrahepatic tissues have been complicated by the use of a single experimental tissue, few animal species, and variable experimental conditions. In an attempt to minimize these complications, liver, lung and kidney from rat, mouse, rabbit, hamster, and guinea pig were assayed for standard microsomal and soluble fraction enzymes involved in drug biotransformation. For all species, liver was the most active organ. Kidney and lung activities were usually 15%-40% of those found in liver, with kidney slightly more active than lung. No single species demonstrated total superiority in its drug-metabolizing ability, although hamster showed a large number of instances of greatest activity. The rat was a surprisingly poor representative of drug-metabolizing ability; it was superior to the other four species in less than 25% of the instances studied. All species appeared to N-demethylate aminopyrine equally except for high pulmonary and nearly absent renal activities in rabbit and high hepatic activity in hamster. Rat had the lowest level of cytochrome P-450 and low activity of NADPH-cytochrome c reductase. UDP-glucuronyltransferase activity toward the acceptors p-nitrophenol and o-aminophenol was higher in hamster and rabbit than other species. Guinea pig appeared to have the most active soluble fraction enzymes. Mouse lung and kidney had glutathione S-aryltransferase activities 10-fold greater than any other species and comparable to liver activity from rabbit and hamster.
 ...
PMID:Comparison of in vitro drug metabolism by lung, liver, and kidney of several common laboratory species. 24 Jun 55

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.
 ...
PMID:Purification and characterization of two glutathione S-aryltransferase activities from rat liver. 81 Jan 39

Knowledge of the error structure of a given set of experimental data is a necessary prerequisite for incisive analysis and for discrimination between alternative mathematical models of the data set. A reaction system consisting of glutathione S-transferase A (glutathione S-aryltransferase), glutathione, and 3,4-dichloro-1-nitrobenzene was investigated under steady-state conditions. It was found that the experimental error increased with initial velocity, v, and that the variance (estimated by replicates) could be described by a polynomial in v Var (v) = K0 + K1 - v + K2 - v2 or by a power function Var (v) = K0 + K1 - vK2. These equations were good approximations irrespective of whether different v values were generated by changing substrate or enzyme concentrations. The selection of these models was based mainly on experiments involving varying enzyme concentration, which, unlike v, is not considered a stochastic variable. Different models of the variance, expressed as functions of enzyme concentration, were examined by regression analysis, and the models could then be transformed to functions in which velocity is substituted for enzyme concentration owing to the proportionality between these variables. Thus, neither the absolute nor the relative error was independent of velocity, a result previously obtained for glutathione reductase in this laboratory [BioSystems 7, 101-119 (1975)]. If the experimental errors or velocities were standardized by division with their corresponding mean velocity value they showed a normal (Gaussian) distribution provided that the coefficient of variation was approximately constant for the data considered. Furthermore, it was established that the errors in the independent variables (enzyme and substrate concentrations) were small in comparison with the error in the velocity determinations. For weighting in regression analysis the inverted value of the local variance in each experimental point should be used. It was found that the assumption of proportionality between variance and valpha (where alpha is an empirically determined exponent) was a good approximation for the weighting. The value of alpha was 1.6 in the present case. The weight function was tested in the fitting of a rate equation to a kinetic-data set involving variable substrate concentrations. Recommendations are given regarding the establishment of the error structure in a general case and its application in regression analysis.
 ...
PMID:Error structure of enzyme kinetic experiments. Implications for weighting in regression analysis of experimental data. 99 63

We have analyzed the cis-acting regulatory DNA elements of the placental rat glutathione S-alkyltransferase (GST-P) gene. Various regions of the 5' flanking sequence were fused with a bacterial chloramphenicol acetyltransferase gene. The transcriptional activity of each construct was determined by the transient expression assay after introduction into a hepatoma cell line. Multiple regulatory elements were identified. Two enhancing elements were located 2.5 and 2.2 kilobases upstream from the transcription start site and designated GST-P enhancers I and II (GPEI and GPEII, respectively). A consensus sequence of the phorbol 12-O-tetradecanoate 13-acetate responsive elements was present in the GPEI and at position -61. GPEII contained two of the simian virus 40 and one of the polyoma enhancer core-like sequences. A silencing element was also found 400 base pairs upstream from the cap site. In accordance with the above observation, endogenous GST-P gene was found to be stimulated when the rat fibroblast line 3Y1 was treated with phorbol 12-O-tetradecanoate 13-acetate. Phorbol 12-O-tetradecanoate 13-acetate enhanced the expression of the transfected GST-P gene to a much higher degree in HeLa cells than in the hepatoma cells, which constitutively expressed the endogenous GST-P. The results are discussed in terms of the specific derepression of GST-P gene during hepatocarcinogenesis in the rat.
 ...
PMID:Multiple regulatory elements and phorbol 12-O-tetradecanoate 13-acetate responsiveness of the rat placental glutathione transferase gene. 320 Aug 31

Using gel filtration, the binding of both glutathione and Bromsulphthalein (BSP) to a liver-soluble protein was found to be identical. BSP-conjugating activity (glutathione S-aryltransferase) was present only in the fractions corresponding to the two protein-bound markers. Using a highly sensitive assay, with 3,4-dichloronitrobenzene, the pattern of glutathione S-aryltransferase activity was found to coincide with Y protein. This evidence suggests that Y protein, or ligandin, has a dual role in hepatic transport: a specific enzymic function in the conjugation of certain anions with glutathione in addition to a transport function in the intracellular binding of organic anions.
 ...
PMID:Role of hepatic anion-binding protein in bromsulphthalein conjugation. 471 80

1. The name ;glutathione S-aralkyltransferase' is proposed for the enzyme catalysing the reaction of benzyl chloride with GSH. 2. Results from heat-inactivation studies, ammonium sulphate-fractionation and acid-precipitation experiments, and studies of the distribution of activities in rat liver, in rat kidney and in the livers of other animals indicate that glutathione S-aralkyltransferase differs from glutathione S-alkyltransferase, S-aryltransferase, S-epoxidetransferase and an S-alkenetransferase. 3. The distribution of these enzymes in the livers of the animal species examined was different. 4. Glutathione S-alkyltransferase, S-aralkyltransferase and the S-alkenetransferase that are present in rat liver supernatant were inhibited by GSSG, and the nature of the inhibition varied in each case. 5. 3,5-Di-tert.-butyl-4-hydroxybenzyl acetate reacts spontaneously with GSH, but the rat liver-supernatant-catalysed reaction of GSH with this and other aralkyl esters was weak. 6. A probable function of the glutathione S-transferases is the protection of cellular constituents from strong electrophilic agents.
 ...
PMID:Glutathione S-aralkyltransferase. 536 Jul 27

The inhibition of DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] dehydrochlorinase and glutathione S-aryltransferase by diphenylmethane and triphenylmethane derivatives was examined. Bis-(3,5-dibromo-4-hydroxyphenyl)methane and similar compounds were excellent inhibitors of both enzymes, but only DDT dehydrochlorinase was inhibited by compounds similar to bis-(N-dimethylaminophenyl)methane. Colour salts of the basic triphenylmethyl dyes were excellent inhibitors of both enzymes. All the inhibitors examined appeared to act by competition with glutathione for its binding site on the two enzymes.
 ...
PMID:The inhibition of 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (DDT) dehydrochlorinase and glutathione S-aryltransferase in grass-grub and housefly preparations. 545 19

1. Heat-inactivation experiments, ammonium sulphate-fractionation studies, enzyme-inhibition studies with S-(alphabeta-diethoxycarbonylethyl)glutathione, and evidence from the distribution of activities in rat liver, in rat kidney and in the livers of other animals, indicate that reactions of glutathione with (i) trans-benzylideneacetone, (ii) cyclohex-2-en-1-one, (iii) trans-cinnamaldehyde, (iv) diethyl maleate, (v) diethyl fumarate and (vi) 2,3-dimethyl-4-(2-methylenebutyryl)phenoxyacetic acid are catalysed by different enzymes. 2. Evidence is presented that the enzymes catalysing the reactions of glutathione with substrates (i)-(iv) are different from glutathione S-alkyltransferase, S-aryltransferase and S-epoxidetransferase. 3. The name ;glutathione S-alkenetransferases' is proposed for enzymes catalysing reactions of glutathione with alphabeta-unsaturated compounds. 4. The Arrenhius plot for the enzyme-catalysed reaction of diethyl maleate with glutathione is discontinuous, with lower energy of activation at 38 degrees .
 ...
PMID:Enzymes catalysing conjugations of glutathione with alpha-beta-unsaturated carbonyl compounds. 568 12


1 2 Next >>