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)

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.
 ...
PMID:Mechanism for the several activities of the glutathione S-transferases. 97 64

Experiments were designed to determine the efficacy of different types of liver cell proliferative stimuli given during exposure to several liver tumor-promoting regimens, on the formation of foci of enzyme-altered hepatocytes. Male Wistar rats were initiated with diethylnitrosamine (150 mg/kg body wt). After a 2 week recovery period animals were subjected to promoting regimens, the resistant hepatocyte model, the phenobarbital model and the orotic acid model. While the rats were on these regimens they were given liver cell proliferative stimulus, either a compensatory type (two-thirds partial hepatectomy or a necrogenic dose of carbon tetrachloride) or a direct hyperplastic stimulus such as that induced by the primary mitogen, lead nitrate. Initiated cells so promoted by these regimens were monitored as foci of enzyme-altered hepatocytes positive for gamma-glutamyltransferase and placental glutathione S-transferase or deficient for adenosine triphosphatase. While carbon tetrachloride and partial hepatectomy-induced compensatory regeneration stimulated the promoting ability of the regimens used, direct hyperplasia could not stimulate the formation of foci and/or nodules from initiated hepatocytes. Evaluation of thymidine incorporation indicated that there was no significant difference in the extent of DNA synthesis in both the proliferative stimuli irrespective of the promoting procedure used.
 ...
PMID:Mitogen-induced liver hyperplasia does not substitute for compensatory regeneration during promotion of chemical hepatocarcinogenesis. 134 15

We have demonstrated that a filamentous fungus Phanerochaete chrysosporium converts glyceryl trinitrate (GTN) into its di- and mononitrate derivatives concurrently with the formation of nitric oxide detected by electron paramagnetic resonance (EPR), and the formation of nitrite. The metabolisms of nitrite and nitrate by the fungus are evaluated and taken into account when considering GTN degradation. Lack of evidence for nitrate formation from GTN suggests that an esterase-type activity is not involved. Furthermore, the kinetics of appearance of the hemoprotein-NO and non-heme protein-NO (FeS-NO) complexes indicate that an enzymatic process producing NO directly from GTN may be involved concurrently with a glutathione transferase-like system.
 ...
PMID:Nitroglycerin metabolism by Phanerochaete chrysosporium: evidence for nitric oxide and nitrite formation. 164 2

Glutathione S-transferases 1-1, 3-3, 3-4 and 4-4 from rat liver and the major glutathione S-transferase from the wax moth (Galleria mellonella) are all inhibited by several simple inorganic anions. For each of 3-3, 3-4 and the insect enzyme, the order of inhibitory potency was ClO4- greater than or equal to SCN- greater than I- greater than NO3- greater than Br-. A more limited range of anions was tested on the isoenzymes 1-1 and 4-4, but the same trend was apparent. Values for Ki ranged from about 200 mM for Cl- to 6 mM for SCN- in the case of the insect enzyme and from 50 mM for Br- to 0.3 mM for SCN- for the rat isoform 3-3. Acetate, F-, SO4(2-) and PO4(3-) were not found to have significant inhibitory properties. The mode of inhibition was characterized as non-competitive in the case of the insect enzyme and rat transferase 1-1, whereas the mode of inhibition was partially non-competitive in the case of the rat isoforms 3-3, 3-4 and 4-4.
 ...
PMID:Inhibition by inorganic anions of glutathione S-transferases from insect and mammalian sources. 188 29

The glutathione transferase (GST) activity of rat liver cytosolic preparations with ethacrynic acid (EA) and (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydro-benzo(a)pyrene (BPDE) as substrates, increased by 125 and 350%, respectively, in animals that had been treated with a single intravenous dose of Pb(NO3)2 (100 mumol/kg body wt) 48 h prior to sacrifice, whereas activity with 1-chloro-2,4-dinitrobenzene (CDNB) increased only about 60%. No induction of these activities was observed in cytosolic preparations from regenerating rat liver, whereas cytosols prepared from hepatocyte nodules showed increased activity with all three substrates (EA: 400%; BPDE: 790%; CDNB: 205%). These results suggest that Pb(NO3)2 is an inducer of GST 7-7, an isoenzyme that has been associated with hepatocarcinogenesis. Elucidation of the mechanism of GST 7-7 induction by lead may contribute to our understanding of the process of chemical carcinogenesis.
 ...
PMID:Induction of rat liver glutathione transferase isoenzyme 7-7 by lead nitrate. 248

The in vitro spasmolytic activity of glycerol trinitrate was measured on the KCl-contraction of aorta strips from the rabbit. In the presence of sulphobromophthalein, a known inhibitor of glutathione S-transferase, the dose-activity curve for the nitrate was displaced to the right. Much smaller displacements were obtained with the control spasmolytic substances--papaverine and S-nitroso-N-acetylpenicillamine. It was confirmed that sulphobromophthalein inhibits glutathione S-transferase activity in aorta homogenates. Aorta extracts did not detectably catalyze the reaction between glutathione and sulphobromophthalein and the glutathione level was not decreased by treating the intact aorta with sulphobromophthalein. It is concluded that sulphobromophthalein acts as a specific antagonist of the spasmolytic activity of glycerol trinitrate, probably as a result of its inhibition of glutathione S-transferase. It thus seems probable that glutathione and glutathione S-transferase are involved in the pharmacological activation of the organic nitrates.
 ...
PMID:Antagonism of glycerol trinitrate activity by an inhibitor of glutathione S-transferase. 250 Jan 24

The effect of a single dose of lead nitrate (10 microM/100 g body wt), a hepatic mitogen, on rat liver glutathione transferase (GST) subunit expression was investigated. Using SDS-polyacrylamide gel electrophoresis and Western blot technique evidence for the induction of GST 7-7 is shown. This occurrence is identical to that observed in preneoplastic nodules generated in rat liver by different models of chemical carcinogenesis, suggesting that lead nitrate may be a very simple model for investigation of the mechanism of glutathione transferase 7-7 gene expression in chemical hepatocarcinogenesis.
 ...
PMID:Induction of rat liver glutathione transferase subunit 7 by lead nitrate. 276 57

Experiments were designed to determine whether liver cell proliferation induced by direct mitogens is as effective as compensatory cell proliferation consequent to previous cell loss, in supporting the growth of enzyme-altered islands in the liver induced by chemical carcinogens. Male Wistar rats were given injections of a single nonnecrogenic dose of N-methyl-N-nitrosourea or benzo(a)pyrene during the S phase following the administration of four different liver mitogens, namely, lead nitrate, ethylene dibromide, nafenopin, and cyproterone acetate, or during compensatory cell proliferation following partial hepatectomy or a necrogenic dose of CCl4. The carcinogen-altered hepatocytes were monitored as gamma-glutamyltransferase- or placental glutathione S-transferase-positive foci using a 2-wk promoting regimen consisting of 0.03% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results indicate that, unlike compensatory cell proliferation induced by partial hepatectomy or CCl4, the mitogen-induced cell proliferation did not result in a significant number of enzyme-altered islands, despite the fact that the extent of cell proliferation at the time of carcinogen administration, as monitored by the examination of labeled cells, is similar with both types of proliferative stimuli.
 ...
PMID:Inability of mitogen-induced liver hyperplasia to support the induction of enzyme-altered islands induced by liver carcinogens. 288 25

The effect of a single administration of lead nitrate on the activity of gamma-glutamyltranspeptidase (gamma-GT), adenosine triphosphatase (ATPase), the placental form of glutathione S-transferase (GST-P) and adenylate cyclase (AC), four enzymes widely used as phenotypic markers for preneoplasia, was investigated in the liver of male Wistar rats. The results of the histochemical enzymatic staining indicated that an acute treatment with lead nitrate induces the activity of gamma-GT, mainly in the hepatocytes located around zone I of the liver acinus, with a maximum seen between 72-96 hours. On the other hand, the activity of ATPase was found to be severely inhibited at 2-3 days after treatment, as shown by a strong decrease in the staining of the bile canaliculi of zones II and III. Immunohistochemical analysis revealed that lead nitrate administration also resulted in the appearance in most of the hepatocytes of GST-P, an enzyme whose activity is almost undetectable in normal rat liver, but is elevated in preneoplastic liver lesions. Finally, lead nitrate treatment resulted in an inhibition of AC activity which was maximal after 24 hours.
 ...
PMID:Modulation of the activity of hepatic gamma-glutamyl transpeptidase, adenosine triphosphatase, placental glutathione S-transferase and adenylate cyclase by acute administration of lead nitrate. 290 38

The administration of a single dose of lead nitrate to male Wistar rats caused an increase of a polypeptide in the liver cytosol that cross reacted with the anti-rat antibody of the placental form of glutathione S-transferase (GST-P). GST-P appeared when doses of lead that induced liver cell proliferation were given (5 and 10 micromoles/100 g of body weight). Recently, it has been shown that rat hepatic nodules also exhibited an increased content of the placental form of GST-P. The induction of GST-P by lead together with other biochemical effects exerted in the liver by this metal, suggests that some chemicals may induce in rat liver a biochemical pattern similar, in some aspects, to that exhibited by carcinogen-induced hepatocyte nodules.
 ...
PMID:Induction of the placental form of glutathione S-transferase by lead nitrate administration in rat liver. 311 22


1 2 3 4 5 6 7 8 Next >>