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)

We examined the change in glutathione metabolism in vitamin B-6-deficient rats. Vitamin B-6-deficient rats were fed a vitamin B-6-deficient diet containing 0.56% methionine and 0.075% cystine for 8 wk. Controls were fed an identical diet supplemented with 10 mg pyridoxine hydrochloride/kg diet. Glutathione concentrations in each organ examined were similar in control and vitamin B-6-deficient rats, and the values were comparably lower after intraperitoneal injection of diethylmaleate. However, buthionine sulfoximine caused a significantly greater decrease in glutathione levels in the liver and lungs of vitamin B-6-deficient rats relative to controls. Glutathione peroxidase activity in the liver of vitamin B-6-deficient rats was higher than in control animals; however, glutathione transferase activity in tissues other than liver of vitamin B-6-deficient rats was higher than in the controls. The activities of gamma-glutamyl-transferase in the liver and spleen of vitamin B-6-deficient rats were significantly lower than control values. The holoenzyme activities of cystathionine beta-synthase and cystathionine gamma-lyase in the liver of vitamin B-6-deficient rats were markedly reduced. These findings indicate that although the activities of enzymes that synthesize cysteine from methionine were decreased by vitamin B-6 deficiency, the level of synthesis and supply of cysteine in vitamin B-6-deficient rats were sufficient to maintain the same glutathione level as in controls, and that glutathione utilization in the liver was accelerated by vitamin B-6 deficiency.
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PMID:Glutathione levels and related enzyme activities in vitamin B-6-deficient rats fed a high methionine and low cystine diet. 188 Jun 14

Glutathione metabolism was studied in isolated hepatocytes from foetal, newborn and adult rats. The GSH/GSSG ratio decreased 15-20-fold through the foetal-neonatal-adult transition. This was mainly due to an increase in GSSG. All enzyme activities involved in the glutathione redox cycle tend to increase during that transition, but the relative increases in glutathione peroxidase and glutathione S-transferase were 3-5 times those of glutathione reductase or glucose-6-phosphate dehydrogenase. GSH synthesis from methionine as a sulphur source was 6 times lower in foetal than in adult hepatocytes. However, when N-acetylcysteine was used as a sulphur donor to by-pass the cystathionine pathway, the rates of GSH synthesis were similar in foetal and adult cells. This is due to the fact that cystathionase activity in foetal cells is very low. This low activity is reflected in the blood amino acid pattern, where the concentration of cysteine rises from 8 to 52 microM from foetuses to adult rats. This supports the idea that cysteine may be an essential amino acid for the premature animal.
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PMID:Physiological changes in glutathione metabolism in foetal and newborn rat liver. 201 16

The inclusion of rats aboard Spacelab 3 (SL-3) allowed analyses of liver lipids, glycogen, hepatic enzymes of cholesterol, glycerolipid and sphingolipid biosynthesis, and other enzyme activities. Glycogen content was markedly elevated in livers from the flight animals compared with controls. Cholesterol was 24% (P less than 0.04) lower in livers from the experimental groups, whereas blood cholesterol was 19% higher (P less than 0.05). The activity of 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme of steroid biosynthesis, was 80% lower (P less than 0.01). Total phospholipids and sphingolipid levels did not differ significantly. The specific activity of fatty acyl-CoA synthetase, which is responsible for activation of fatty acids, was 37% (P less than 0.05) higher in microsomes from the rats on SL-3; however, since these animals had 25% less microsomal protein (P less than 0.02), there was no difference per gram of liver. The initial enzymes of sphingolipid and glycerolipid biosynthesis were assayed; serine palmitoyltransferase was 40% lower (P less than 0.01), and glycerol 3-phosphate acyltransferase did not differ. Hepatic cytochrome P-450 content decreased by 50% after spaceflight. Enzymes that did not differ significantly between the two groups include cytochrome b5, glutathione S-transferase, tyrosine aminotransferase, aspartate aminotransferase, and cystathionase. These findings suggest that spaceflight alters hepatic metabolism of several classes of compounds.
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PMID:Hepatic function in rats after spaceflight: effects on lipids, glycogen, and enzymes. 381 60

The aim of the present study was to examine the protective effect of cystathionine as a cysteine precursor on doxorubicin toxicity in the liver of Ehrlich ascites tumor (EAT)-bearing mice and in the EAT cells. Both compounds were injected intraperitoneally alone or in combination at the following doses: cystathionine at 10 mg and doxorubicin at 5 mg per kg of body weight. In the liver of EAT-bearing mice, glutathione (GSH), cysteine and sulfane sulfur levels as well as the activities of: glutathione S-transferase, gamma-glutamyl transpeptidase, rhodanese and gamma-cystathionase significantly dropped in comparison with healthy animals. Administration of cystathionine elevated GSH and cysteine levels in the livers of EAT-bearing mice and reduced lipid peroxidation. Furthermore, cystathionine increased gamma-glutamyl transpeptidase activity, thereby activating gamma-glutamyl cycle, responsible for proper glutathione metabolism in the cells. Cystationine did not influence sulfane sulfur level and rhodanese and gamma-cystathionase activity in the livers of EAT-bearing mice. It was next shown that cystathionine administered in combination with doxorubicin protected against the drug toxicity since it elevated thiol level, lowering reactive oxygen species content and suppressing lipid peroxidation. This means that, cystathionine in the liver of EAT-bearing mice can both correct harmful effects of carcinogenesis, and protect the liver from doxorubicin cytotoxicity. In contrast, in EAT cells, cystathionine lowered GSH and cysteine levels and did not alter reactive oxygen species level, lipid peroxidation, and gamma-glutamyl transpeptidase activity. All these data indicate that cystathionine action is selectively beneficial for normal cells because it corrects harmful effects induced by EAT development and protects the organism against doxorubicin cytotoxicity without impairing cytotoxicity of this drug to tumor cells.
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PMID:The selective effect of cystathionine on doxorubicin hepatotoxicity in tumor-bearing mice. 1703 87

Tumor cells, unlike normal cells, are characterized by trace cystathionase (CST) activity and sulfane sulfur levels. The present studies aimed to established whether cystathionine (CT), a substrate of cystathionase, can selectively influence the thiol-dependent antioxidant power of the kidney and Ehrlich ascites tumor (EAT). CT treatment reversed the changes in renal concentrations of non-protein thiols (NPSH), reactive oxygen species (ROS), sulfane sulfur and activities of rhodanese, cystathionase and glutathione S-transferase (GST) in tumor-bearing mice, which returned to the level observed in healthy animals. The results demonstrated that CT corrected all harmful changes in the mouse kidney induced by EAT. In contrast, CT did not elicit such effect in EAT cells, in which it only increased ROS level. It indicates that CT can selectively protect the kidney of tumor-bearing mice against nephrotoxicity of drugs as well as restore biological function of sulfane sulfur. On the other hand, cisplatin (CP) did not affect any of the parameters under study in the kidney of tumor-bearing mice. Interestingly, cisplatin markedly lowered glutathione S-transferase activity and increased sulfane sulfur level and rhodanese activity in tumor cells. It is also worth noting that CP doses devoid of nephrotoxic effect in tumor-bearing mice could enhance cystathionine action on the kidney, causing an additional increase in NPSH and CST and rhodanese activity.
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PMID:Nephroprotective effect of cystathionine is due to its diverse action on the kidney and Ehrlich ascites tumor cells. 1804 56