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)

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

The 97-kDa protein Mtx21, derived from the 100-kDa mosquitocidal protein (Mtx) from Bacillus sphaericus SSII-1 by the deletion of the putative signal sequence, was expressed as a fusion protein with glutathione S-transferase in Escherichia coli, and the fusion protein was purified by affinity chromatography. The fusion protein bound to glutathione agarose was cleaved with thrombin to release the Mtx21 protein. The 97-kDa Mtx21 protein was found to be toxic to Culex quinquefasciatus larvae with a 50% lethal concentration of 15 ng/ml. Treating Mtx21 with crude mosquito larval gut extracts gave rise to two major peptides of 70 and 27 kDa. Treating the 97-kDa Mtx21 protein with trysin also gave rise to a similar proteolytic cleavage pattern. N-terminal sequencing showed that the 27-kDa peptide was derived from the N-terminal region of the 97-kDa protein and that the 70-kDa protein was from the C-terminal region of the 97-kDa protein. The 27-kDa peptide has all the previously identified regions of homology with the catalytic peptides of the ADP-ribosyltransferase toxins, such as pertussis toxin S1 peptide, while the 70-kDa peptide has three internal regions of homology.
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PMID:Proteolytic processing of the mosquitocidal toxin from Bacillus sphaericus SSII-1. 135 68

Highly larvicidal strains of Bacillus sphaericus produce a binary toxin composed of 51 and 42 kDa proteins which binds to sharply delineated regions of the gastric caecum and posterior midgut of susceptible larvae of the mosquito Culex quinquefasciatus. To investigate the role of the individual subunits and the organization of functional binding regions within the toxin, plasmids were constructed for the expression in Escherichia coli of the toxin proteins and their NH2- and COOH-terminal deletion derivatives as fusions with glutathione S-transferase (GST). Toxin proteins were purified by affinity chromatography followed by cleavage from the GST carrier with thrombin. The LC50 values for the purified toxin proteins and their deletion derivatives were determined. The binding patterns of fluorescently labelled toxin suggested that the 51 kDa protein is the primary binding component of the toxin and mediates the regional binding and internalization of the 42 kDa protein. Examination of the toxin deletion derivatives revealed that the NH2-terminal region of the 51 kDa protein was required for binding to the larval gut, whilst the COOH-terminal region was responsible for interacting with the 42 kDa protein. Toxicity was strongly correlated with the subsequent internalization of the toxin, probably by endocytosis.
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PMID:Binding of purified Bacillus sphaericus binary toxin and its deletion derivatives to Culex quinquefasciatus gut: elucidation of functional binding domains. 151 80

1. Glucosinolate-rich diet (RM) in growing rats increased liver (a), kidneys (b), and thyroid (c) weights and depleted feed intake (d), growth curve (e) and T4 and T3 plasma levels (f). 2. Oral administration of phenobarbital enhanced the toxic effect of RM on (b), (d) and (e) and did not modify the toxic effect of RM on (a), (c) and (f). 3. RM had a depleting effect on hepatic microsomal P-450 specific activity. 4. RM had an enhancing effect on hepatic glutathione S-transferase and UDP-glucuronyltransferase specific activities. 5. These results indicate that some glucosinolate derivatives released by gut microflora metabolism are further metabolized by the hepatic detoxification system, and that they could play the role of co-toxic or co-detoxic molecules.
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PMID:Glucosinolates toxicity in growing rats: interactions with the hepatic detoxification system. 211 Mar 94

1. Using a specific and sensitive GLC method for the determination of glyceryl trinitrate (GTN), its subcellular and tissue distribution were reassessed. Liver was the most active tissue, but activity was also detected in the heart, kidney and gut. In all tissues activity was localized in the soluble fraction. The activity of soluble glutathione S-transferase followed the same pattern, liver exhibiting the highest and the heart the lowest activity. 2. Pretreatment with phenobarbitone and 3-methylcholanthrene stimulated both the glutathione S-transferase and organic nitrate reductase activities. 3. Glutathione S-transferase activity was competitively inhibited by GTN. 4. A comparison of the plasma and hepatic metabolism of GTN revealed higher drug affinity for the hepatic enzyme.
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PMID:Organic nitrate reductase: reassessment of its subcellular localization and tissue distribution and its relationship to the glutathione transferases. 250 45

1. The activities of the ethoxycoumarin O-deethylase (ECOD), epoxide hydrolase (EH), UDP-glucuronyl transferase (GT), glutathione S-transferase (GST), acetyl transferase (AT) and sulphotransferase (ST) were measured in 6 liver, 8 lung, 8 kidney, 8 intestinal mucosa and 22 urinary bladder mucosa specimens from human subjects. EH and GT were studied with styrene oxide and 1-naphthol, respectively, as substrates, GST, AT and ST were studied with benzo(a)pyrene-4,5-oxide, p-aminobenzoic acid and 2-naphthol, respectively. 2. The enzyme activities were detectable at significant rates in liver, lungs, kidneys and gut. In urinary bladder, EH, GT, GST and ST only were detectable. The liver catalyzed the various reactions at higher rates than did other tissues. 3. Of the extrahepatic tissues, the intestinal mucosa contained the highest activities of AT (50% of liver) and ST (30% of liver), whereas kidneys contained the highest activity of GT (50% of liver) and GST (80% of liver). GST was the enzyme with the widest tissue distribution.
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PMID:Tissue distribution of drug-metabolizing enzymes in humans. 314 May 1

The gastrointestinal tract forms the first line of defense in the body against the main load of xenobiotics. The gastrointestinal mucosa has several mechanisms through which the xenobiotics are modified. The monooxygenase activities in most species are relatively low in the mucosa as compared to the liver, but conjugation, for example, via glucuronide formation proceeds efficiently. UDP-glucuronosyltransferase activities can exceed those in the liver. Glutathione S-transferase activity is also high. The biotransformation activities are readily inducible in the mucosa and this is, at least partly, responsible for the oral-aboral gradient seen in enzyme activities. In rainbow trout glutathione S-transferase is, however, significantly higher at the aboral third than in two oral segments, although in rats the intestinal glutathione S-transferase shows a clear oral-aboral gradient. The gradient is independent of the presence of microflora at least in the case of carboxylesterase and glutathione S-transferase. A similar gradient can also be found from the gut lumen, in both germ-free and specific pathogen-free rats. The cells in the middle of the villi appear to be most responsive under the influence of inducers. The readily occurring induction in the mucosa provides a suitable model for studies on biological effects to defined compounds and mixtures.
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PMID:Role of gut in xenobiotic metabolism. 330 15

A specific radioimmunoassay (RIA) has been developed that has sufficient sensitivity to allow measurement of the changes in plasma and tissue glutathione S-transferase (GST) YaYa concentrations which occur following thyroid hormone administration in the rat. Using the RIA it was demonstrated that the only tissues that had significant amounts of GST YaYa were liver, small gut and kidney. Administration of triiodothyronine (T3) or thyroxine (T4) resulted in increases in plasma GST YaYa concentration and in animals given high doses of T4 plasma alanine aminotransferase activity was also elevated. Thyroid hormone administration produced a significant fall in the hepatic content of GST YaYa and in total GST activity, as assessed using 1-chloro-2,4-dinitrobenzene as substrate. It is concluded that the elevated plasma GST YaYa concentrations observed following administration of thyroid hormones result from hepatic damage, not from induction of hepatic synthesis of the enzyme.
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PMID:Hepatic damage in the rat following administration of thyroxine or triiodothyronine, assessed by measurement of plasma glutathione S-transferase YaYa concentrations. 381 55

Four cDNA clones (GST-1, -7, -47, and -51) encoding isoenzymes of the detoxification enzyme glutathione S-transferase (GST) have previously been identified and characterised from Fasciola hepatica. In the present study, antisera were generated to synthetic peptides of regions unique to each of the four GST proteins predicted by the cDNAs. The antisera were characterised, and two were found to distinguish GST-1 from GST-7, GST-47, and GST-51 as a group. These two antisera were used to localise different GSTs in adult and newly excysted juvenile F. hepatica. The antiserum to GST-1 was specific and localised GST-1 to the parenchyma of adult fluke but not to the lamellae of the intestinal caeca. The antiserum to a GST-51 peptide, which cross-reacted with GST-7 and GST-47 but not GST-1, localised the other GSTs not only to the parenchyma but also to the intestinal lamellae of adult fluke. This appears to be the first evidence of tissue-specific expression of GST isoenzymes in trematodes. In contrast to adult fluke, immunolocalisation of the GSTs in juvenile F. hepatica revealed the binding of both the GST-1 and GST-51 antisera to the parenchymal cytoplasm, to cytoplasmic extensions of the parenchyma cells in the subtegumental area, as well as the excretory ducts. No labeling was observed in the intestinal epithelium of the juvenile fluke. These results demonstrate that adult F. hepatica, in contrast to juvenile flukes, contain a GST, which is not GST-1, associated with the lamellae of the gut and suggest that GSTs in adult fluke may play a role in the absorptive function of the adult gut.
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PMID:Fasciola hepatica: localisation of glutathione S-transferase isoenzymes in adult and juvenile liver fluke. 762 58

Omeprazole induces CYP1A in the human liver and gut, which has led to concern about possible side effects. The purpose of this study was to compare the effects of omeprazole on phase 1 and phase 2 enzymes in the rat and human. Male rats were treated with intraperitoneal (40 or 80 mg/kg) or oral omeprazole (40 mg/kg) for 5 or 14 days, respectively. The activities and amounts of CYP1A, uridine diphosphate-glucuronosyltransferase, and glutathione transferase were determined in liver and gut. Enzyme activities were also determined in duodenal biopsy specimens from six healthy human volunteers before and after treatment with omeprazole (20 mg/day) for 10 days. Treatment with intraperitoneal omeprazole (40 mg/kg; 80 mg/kg) coinduced uridine diphosphate-glucuronosyltransferase (36%; 66%), glutathione transferase (22%; 50%), and CYP1A (26%; 50%) in rat liver. In rat small intestine, comparable levels of induction were observed for uridine diphosphate-glucuronosyltransferase and glutathione transferase; CYP1A was unaffected. Oral omeprazole had similar effects. Immunoblotting showed corresponding changes in the amounts of these enzymes. Omeprazole increased the activities of CYP1A (19% to 167%; p = 0.014) and uridine diphosphate-glucuronosyltransferase (11% to 68%; p = 0.04) in the duodenal biopsy specimens of all six human volunteers; glutathione transferase was unaffected. Thus, omeprazole coinduced multiple xenobiotic metabolizing enzymes in the rat and human. The pattern of induction differed in the rat and human, consistent with known differences in genetic regulatory elements in the two species.
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PMID:Comparative effects of omeprazole on xenobiotic metabolizing enzymes in the rat and human. 852 27


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