Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 natural occurrence of gamma-glutamyl-glutathione (gamma-glutamyl-gamma-glutamylcysteinylglycine) in bile was established by analytical and chromatographic studies on the isolated and chemically synthesized materials. Evidence that it is formed in kidney was obtained. The origin of gamma-glutamyl-glutathione was explored through studies on the interaction of glutathione with gamma-glutamyl transpeptidase. When purified gamma-glutamyl transpeptidase was incubated with various concentrations (4 microM-50 mM) of glutathione, the initial rates of formation of gamma-glutamyl-glutathione were substantial at all concentrations of glutathione studied and were greater than the rates of formation of glutamate at physiological levels of glutathione (1-10 mM). The findings indicate that gamma-glutamyl transpeptidase catalyzes transpeptidation in vivo. That gamma-glutamyl-glutathione is formed in vivo and that it is a significant product of the reaction between glutathione and gamma-glutamyl transpeptidase under physiological conditions suggest that this polyanionic tetrapeptide may have a physiological role. gamma-Glutamyl-glutathione is not a substrate of glutathione reductase or of glutathione S-transferase, but it is a substrate of gamma-glutamyl-cyclotransferase. That gamma-glutamyl-glutathione has an additional negative charge as compared to glutathione suggests that it may be more effective than glutathione in forming complexes with certain metal ions and other cations.
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PMID:Gamma-glutamyl-glutathione. Natural occurrence and enzymology. 287 99

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

We measured the contents of amino acids and related amino compounds in autopsied brain from 22 patients with Alzheimer's disease (AD) and in cortical biopsy specimens from 2 other patients. The diagnosis of AD was established neuropathologically in all 24 patients by the presence of both neurofibrillary tangles and neuritic plaques in neocortex. The mean contents of gamma-aminobutyric acid (GABA), and of the GABA dipeptide homocarnosine, were significantly reduced in frontal and occipital cortices and in hippocampus of the autopsied brains of AD patients compared to control patients without neurological disease. However, GABA contents were normal in frontal cortex in biopsy samples from 2 patients. Phosphoethanolamine contents were significantly reduced at autopsy in frontal and occipital cortex, and in the substantia innominata. We found no evidence of a deficiency of glutamate, aspartate, or taurine in AD brain, as has been claimed. Glutathione contents and glutathione transferase activities were normal in frontal cortex and substantia innominata. The mechanism of neuronal death in patients with AD is unlikely to involve either insufficient synthesis of glutathione or failure to conjugate free radicals with glutathione.
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PMID:Amino acids, glutathione, and glutathione transferase activity in the brains of patients with Alzheimer's disease. 357 18

The oxygen analogue, gamma-L-Glu-L-SerGly (GOH) and desthio analogue, gamma-L-Glu-L-AlaGly (GH) have been synthesized by a simple three step procedure involving active ester coupling of N-t-BOC-alpha-(4-nitrophenyl)-L-glutamate to L-SerGly and L-AlaGly, respectively. The two peptides are excellent dead-end inhibitors of isozymes 3-3 and 4-4 of rat liver glutathione S-transferase. At low fixed concentrations of 1-chloro-2,4-dinitrobenzene (CDNB) GOH and GH are linear competitive inhibitors of isozyme 3-3 vs glutathione with KI values of 13.0 and 116 microM, respectively. Both peptides are non-competitive (mixed-type) inhibitors vs CDNB when glutathione is the fixed substrate. Similar results are obtained with both peptides and isozyme 4-4. The results rule out ordered or ping-pong kinetic mechanisms where the electrophile adds first.
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PMID:Synthesis and characterization of the oxygen and desthio analogues of glutathione as dead-end inhibitors of glutathione S-transferase. 398 65

The effects of bromobenzene, carbon tetrachloride, and N-nitrosodimethylamine (DMN) on hepatic glutathione S-transferase activity were studied in untreated and in phenobarbital- or ethanol-treated rats. In phenobarbital-treated rats, the isozymic composition of the hepatic cytosolic glutathione S-transferases was changed after giving hepatotoxic chemicals; glutathione S-transferases 2-2(AA), 3-3(A), 1-2(B), 3-4(C), and 4-4 + 5-5(D + E) were present in cytosol from control rats, but only glutathione S-transferases cochromatographing with transferases 4-4 + 5-5(D + E) were detected in rats given carbon tetrachloride or bromobenzene. A marked decrease in hepatic and an increase in serum glutathione S-transferase activity were also observed after carbon tetrachloride or bromobenzene treatment, but little change was seen after giving DMN. On the contrary, in untreated or ethanol-treated rats, DMN administration decreased hepatic glutathione S-transferase activity and caused an elevation in serum glutathione S-transferase activity. The isozymic composition of the hepatic cytosolic glutathione S-transferases after giving DMN to untreated rats was also altered, but the alteration was much less than that observed after giving carbon tetrachloride or bromobenzene to phenobarbital-treated rats. The elevation in serum glutathione S-transferase activity was accompanied by an increase in both serum glutamate-pyruvate transaminase activity and serum bilirubin concentrations. Thus, hepatic glutathione S-transferase activity was altered and released into serum after giving hepatotoxic chemicals, and the alteration in glutathione S-transferase activity was dependent on treatment with phenobarbital or ethanol.
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PMID:Alteration of hepatic glutathione S-transferases and release into serum after treatment with bromobenzene, carbon tetrachloride, or N-nitrosodimethylamine. 407 84

The relations between serum transaminase activity and the hepatic contents of glutathione and lipid peroxide were examined following oral administration to rats of butylated hydroxytoluene (BHT; 500 or 1000 mg/kg). The glutathione level rapidly diminished and reached a minimum at 6 hr after BHT administration. The period of depletion was dependent on dose: restoration of the glutathione level took longer in high-dose rats than in low-dose rats. The content of hepatic lipid peroxide was not markedly changed by BHT throughout the experimental period. The activity of glutathione S-transferase was not affected until 12 hr after BHT administration but, thereafter, it increased with time and was accompanied by elevation of the glutathione level. Though the activities of serum glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase were not affected by low-dose BHT, they increased rapidly in the high-dose rates after a lag period of about 6 hr and reached a maximum at 24 hr after administration; at that time, the livers of the high-dose rats showed centrilobular necrosis. The results indicate that acute hepatic injury was induced by the high-dose BHT. Pretreatment with cobaltous chloride inhibited the increase in the activities of the serum transaminases produced by the high-dose of BHT accompanying the depletion of microsomal cytochrome P-450 content and the induction of glutathione content. These observations suggest that hepatic damage was associated with prolonged depletion of glutathione rather than with lipid peroxidation in the liver, and that the activated metabolites of BHT rather than the parent compound induced the tissue damage.
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PMID:On the mechanism of butylated hydroxytoluene-induced hepatic toxicity in rats. 646 78

Hepatic glutathione S-transferase activities were determined with the substrates 1,2-dichloro-4-nitrobenzene and 1-chloro-2,4-dinitrobenzene. Sexual differentiation of glutathione S-transferase activities is not evident during the prepubertal period, but glutathione conjugation with 1,2-dichloro-4-nitrobenzene is 2-3-fold greater in adult males than in females. Glutathione conjugation with 1-chloro-2,4-dinitrobenzene is slightly higher in adult males than adult females. No change in activity was observed after postpubertal gonadectomy of males or females. Neonatal castration of males results in a significant decrease in glutathione conjugation with 1,2-dichloro-4-nitrobenzene. Hypophysectomy, or hypophysectomy followed by gonadectomy did result in significantly higher glutathione S-transferase activities in both sexes. These increases can be reversed by implanting an adult male or female pituitary or four prepubertal pituitaries under the kidney capsule. Postpubertal sexual differentiation of glutathione S-transferase activities is neither dependent on pituitary sexual differentiation nor pituitary maturation. Prolactin concentrations are inversely related to glutathione S-transferase activities in hypophysectomized rats with or without ectopic pituitaries. Somatotropin exogenously administered to hypophysectomized rats results in decreased glutathione S-transferase activities, whereas prolactin has no effect. Adult male rats treated neonatally with monosodium l-glutamate to induce arcuate nucleus lesions of the hypothalamus have decreased glutathione S-transferase activities towards 1,2-dichloro-4-nitrobenzene and decreased somatotropin concentrations. Our experiments suggests that sexual differentiation of hepatic glutathione S-transferase is a result of a hypothalamic inhibiting factor in the male (absent in the female). This postpubertally expressed inhibiting factor acts on the pituitary to prevent secretion of a pituitary inhibiting factor (autonomously secreted by the female), resulting in higher glutathione S-transferase activities in the adult male than the adult female.
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PMID:The hypothalamic--hypophyseal--gonadal regulation of hepatic glutathione S-transferases in the rat. 732 95

Ag-NOR proteins are silver-stainable proteins in the nucleolar organizer regions and are used to distinguish benign from malignant tumors. B23 and C23 are the two major Ag-NOR proteins. This study shows that only one of the two acidic clusters of B23 is responsible for its silver staining property. Fusion of this region of B23 (amino acids 161-188) to glutathione S-transferase produced an Ag-NOR positive fusion protein. The same result was obtained when amino acids 233-277 of C23 was fused with glutathione S-transferase. The aspartate residues, but not the glutamate residues, were found to be primarily responsible for the silver staining of the acidic clusters.
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PMID:Specific aspartic acid-rich sequences are responsible for silver staining of nucleolar proteins. 753 2

A recent study from our laboratory demonstrated that cyclosporine (CsA), a prototype immunosuppressant, enhanced the growth of carcinogen-induced enzyme altered foci in rat liver, suggesting that CsA may stimulate development of hepatocellular carcinomas. In the present study, we examined (i) whether CsA accelerates development of hepatocellular carcinomas in experimental animals, (ii) whether CsA stimulates the proliferation of resting hepatocyte in vivo and (iii) whether CsA modulates the production of growth factors implicated in liver cell growth, hepatocyte growth factor (HGF), transforming growth factor alpha (TGF alpha) and transforming growth factor beta 1 (TGF beta 1). Foci of hepatocytes, positive for glutathione S-transferase placental form were induced in male F344 rats by a single dose of diethylnitrosamine followed by 7 weeks promotion by a choline-deficient diet. The animals were then divided in two groups, and subsequent development of hepatocellular carcinomas was compared in rats fed a basal diet or a basal diet containing 0.015% CsA. Development of hepatocellular carcinoma was accelerated in the rats maintained on a CsA diet. Feeding a CsA diet as the sole treatment, for 2, 4 and 10 weeks induced significant increases in liver weight, and resulted also in an enhanced incorporation by hepatocytes of 5-bromo-2-deoxy-uridine. Serum levels of glutamate-oxaloacetate transferase, glutamate-pyruvate transferase and lactic dehydrogenase were not altered by feeding a CsA diet. Northern Blot analyses of the expression of HGF, TGF alpha and TGF beta 1 mRNAs in the liver showed similar patterns of expression between rats fed a basal diet and a CsA diet. The levels of HGF mRNA were not altered in the lungs and kidneys of rats fed a CsA diet. These results indicate that CsA stimulates rat liver cell proliferation in vivo without inducing liver cell necrosis, and that this effect may contribute to accelerated development of hepatocellular carcinomas in rats fed a CsA diet. As previously observed with BR 931, a hypolipidemic peroxisome proliferator, stimulation of liver cell growth by CsA did not entail changes in the production of HGF, TGF alpha or TGF beta 1.
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PMID:Cyclosporine stimulates hepatocyte proliferation and accelerates development of hepatocellular carcinomas in rats. 835 42

The effect of carbon sources, glucose and sucrose, and nitrogen sources such as ammonia, glutamate and L-citrulline on the activities of glutathione metabolic enzymes has been studied. Yeast and mycelial cells were used to identify changes in activity levels of glutathione reductase (GSSGR), glutathione transferase (GST), glutathione peroxidase (GPX) and gamma-glutamyl transpeptidase (GGT). Enzyme activities from cells grown in sucrose media were lower than in glucose media regardless of the enzyme tested, morphological form, or the growth interval. In all enzymes except GST, activity was higher in yeast form than in mycelia, regardless of nitrogen source, with lower activity from 24 to 72 h than at 96 h. In citrulline media, yeast form showed the maximum GST, GGT, and GPX activity. In ammonia-amended media, mycelia showed maximum activity in GGT, whereas in glutamate media, mycelia showed the maximum activity in GST. Also, the type of nitrogen source had no effect on GPX activity in the mycelial form. Finally, changing the nitrogen source showed no significant effect on GSSGR activity, either in the yeast or mycelial form.
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PMID:Influence of carbon and nitrogen sources on glutathione catabolic enzymes in Candida albicans during dimorphism. 853 61


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