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)

1. The levels of GSH-S-epoxidetransferase (GSH-S-transferase E, EC 2.5.1.18), gamma-glutamyl transpeptidase (EC 2.3.2.2) and S-substituted cysteine N-acetyltransferase have been measured in the liver and kidney of neonatal to adult rats. 2. GSH-S-epoxidetransferase and S-substituted cysteine N-acetyltransferase activities were less than 10% of the adult values in neonatal rats, rising gradually to reach adult values at about 40 days of age. Renal gamma-glutamyl transpeptidase activity was 27% of the adult value 2 days after birth and increased after 15 days reaching adult levels by 40 days. 3. The percentages of the doses of 1,2-epoxy-3-(p-nitrophenoxy)propane (ENPP) and of 1,2-epoxybutane, administered at the same dose level to rats aged 4 days to adult, excreted as the corresponding mercapturic acids in 24 h, were not significantly different. 4. Adult and 10 day old rats doses at the same dose level with ENPP excreted N-acetyl-S-[2-hydroxy-3-(p-nitrophenoxy)propyl]-L-cysteine (ENPP-MA) at the same rate. 5. In addition to ENPP-MA, dosed rats under 13 days of age excreted the corresponding substituted cysteine. 6. The correlation between results in vitro and in vivo is discussed.
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PMID:Glutathione conjugation and mercapturic acid formation in the developing rat, in vivo and in vitro. 2 9

The effect of unilateral pneumonectomy on the drug-metabolizing capability of the remaining lung of male rabbits was studied 3, 10, and 28 days after surgery. During the period of compensatory lung growth which follows pneumonectomy, the contralateral lung had a reduced ability to metabolize some model drug substrates. The activities of 4-chloro-N-methylaniline demethylase, glutathione transferase, and 4-aminobenzoate N-acetyltransferase were significantly decreased in pneumonectomizd animals relative to shamoperated controls at 10 days. By 28 days most of these parameters of drug metabolism had returned to control levels. Lung hydroxyproline concentration, an index of collagen, did not differ in pneumonectomized and control animals at any of the time points. 3-Methylcholanthrene failed to induce the pulmonary mono-oxygenase system in pneumonectomized animals. The response of pulmonary drug-metabolizing enzymes to unilateral pneumonectomy in rabbits was temporally and qualitatively similar to the response in rat liver following partial hepatectomy.
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PMID:The effect of unilateral pneumonectomy on in vitro drug metabolism by the contralateral lung of rabbits. 3 21

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.
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PMID:Effect of strain differences and tumor presence on microsomal drug metabolism in the guinea pig: brief communication. 20 Jul 61

Epidemiological studies suggested a protective effect of certain phenotypes of polymorphic foreign-compound-metabolizing enzymes in some types of cancer. Poor metabolizers (PM) of debrisoquine 4-hydroxylase (cytochrome P-450IID6, CYP2D6) were found to be underrepresented among patients with lung cancer. Recent advances in molecular genetic characterization of CYP2D6, glutathione S-transferase (GST) class Mu, and arylamine N-acetyltransferase enabled genotypical determination of mutant alleles in lung cancer patients. Restriction fragment length polymorphism (RFLP) with a cDNA gene probe of CYP2D6 was analyzed in 79 lung cancer patients who were phenotyped with debrisoquine. Mutant alleles were detected by allele-specific polymerase chain reaction (PCR). In the same individuals, genotype of GST class Mu was analyzed by PCR and correlated with ex vivo activity of glutathione conjugation towards trans-stilbene oxide. RFLP patterns allowed discrimination between the slow and fast genotype of N-acetyltransferase as well as the heterozygotes. Three phenotypical PMs of debrisoquine (3.8%) were confirmed by PCR and RFLP. No PM could be unambiguously recognized only by RFLP patterns. The PMs were characterized by PCR and RFLP as carriers of the 29B/29B (n = 1), 29A/29B (n = 1), and 29A/44 (n = 1) mutant alleles. Higher debrisoquine hydroxylase activities were found in the homozygous EMs, who possess two active genes, as compared to heterozygous EMs, who have only one active gene. The patients with phenotypically impaired GST Mu activity were confirmed as such by PCR. A complete correspondence between phenotyping of N-acetyltransferase (with caffeine) and genotyping was found. The new genetic techniques proved to be powerful tools for molecular-epidemiological studies aimed at establishing host factors of cancer susceptibility.
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PMID:Mutant genes of cytochrome P-450IID6, glutathione S-transferase class Mu, and arylamine N-acetyltransferase in lung cancer patients. 135 78

Does chronic voluntary physical activity alter hepatic or intestinal capacities for xenobiotic biotransformation? This question was investigated by comparing biotransformation enzyme activities in liver and small intestine of active and sedentary rats. Male rats allowed unlimited access to a running wheel and fed ad lib. for 6 weeks were weight-matched to sedentary controls; the active rats ate 22% more food than the sedentary rats (P less than 0.05). Active rats ran 2.8 +/- 0.6 miles/day. Liver weights were higher in the active rats (11.2 +/- 0.2 vs 9.8 +/- 0.2 g; P less than 0.05), as were total liver protein, and liver microsomal and cytosolic protein (P less than 0.05). As a result of liver hypertrophy, the active rats showed higher total liver activity of several biotransformation enzymes, including 2-naphthol sulfotransferase, styrene oxide hydrolase, benzphetamine N-demethylase, ethacrynic acid glutathione S-transferase and morphine UDP-glucuronosyltransferase (P less than 0.05). In contrast, there was no detectable difference in total liver N-acetyltransferase activity toward p-aminobenzoic acid, 2-naphthylamine, and 2-amino-fluorene as well as, relative hepatic enzyme activity (expressed per g liver or per mg protein) and total and relative intestinal enzyme activity. We conclude that chronic voluntary physical activity, accompanied by an increased food intake, results in liver hypertrophy and potentially increases total hepatic capacity to biotransform certain xenobiotic chemicals.
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PMID:Chronic physical activity: hepatic hypertrophy and increased total biotransformation enzyme activity. 163 26

To assess the biotransformational capability of ocular tissues in the rabbit, representative phase II enzymes were assayed in five tissues from the eye, and in the liver, kidney, and intestine. Within the eye, the iris/ciliary body exhibited the highest glutathione S-transferase activity, whereas the cornea possessed the highest specific activities for N-acetyl-, sulfo-, and UDP-glucuronosyl-transferases. Cornea, iris/ciliary body, choroid, and retina exhibited significant activities of p-aminobenzoic acid N-acetyltransferase, 2-naphthol sulfotransferase, and 1-chloro-2,4-dinitrobenzene glutathione S-transferase. Despite its size and protein content, lens displayed little or no biotransformational activity. Only the iris/ciliary body conjugated sulfobromophthalein with glutathione. UDP-glucuronsyltransferase activity varied depending on tested substrates and tissues. When compared to liver, kidney, or intestine, N-acetyltransferase activity in the iris/ciliary body nearly matched the rate measured in kidney, glutathione S-transferase activity in cornea and iris/ciliary body was nearly 70 and 89%, respectively, of the rate in intestine, and corneal sulfotransferase activity was greater than that in kidney. These data suggest that biotransformation pathways are present in the eye, and particularly in ocular tissues having adequate blood supply or interfacing with the external environment.
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PMID:Comparative study of phase II biotransformation in rabbit ocular tissues. 168 Jun 41

The comparative distribution of p-nitrophenol UDP-glucuronosyl-transferase, 1-chloro-2,4-dinitrobenzene glutathione-S-transferase and sulphamethazine N-acetyltransferase activities was studied along the gastrointestinal mucosa of female Lacaune sheep. Gastrointestinal mucosa was characterized by a very low and unequal N-acetyltransferase activity when activities were expressed per g of wet organ. The duodenum contained highest activities (4.1 nmol/g min). When results were expressed per mg of cytosolic protein, the duodenal activity (0.64 nmol/mg min) was sixfold higher than in liver (0.11 nmol/mg min). There was a lack in N-acetyltransferase activity accepting isoniazid as substrate. Glucuronosyltransferase activity was approximately threefold higher in microsomal fractions of the mucosal lining of gastric and colonic intestine (0.43-0.58 nmol/g min) than in small intestine or caecum (0.10-0.26 nmol/mg min). Concerning cytosolic glutathione S-transferase activity, two- to threefold higher activities were obtained in omasum, jejunum, duodenum and ileum (1021-2164 nmol/g min) than in other parts (341-799 nmol/g min) when results were expressed per g of wet organ. These data were compared with corresponding hepatic activities determined in the same six female sheep.
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PMID:Comparison of mucosal drug conjugative rates along the gastrointestinal tract of female sheep. 174 35

1. The comparative activity of hepatic cytochrome P-450 monooxygenase system, glucuronyl-transferase, glutathione S-transferase and N-acetyltransferase was studied in three-month-old male and female Lacaune lambs and male Saanen kids. 2. The study of mixed-function oxidase components showed that total cytochrome P-450 ranged from 0.54 in kids to 0.85-0.88 nmol/mg-1 in lambs. Male lambs had higher levels than kids (122-165%) for aminopyrine, benzphetamine, ethylmorphine and erythromycin demethylases or benzo(a)pyrene hydroxylase whereas NADPH-cytochrome c reductase was 1.19-fold lower in lambs. 3. Sex-related changes were observed in lambs in case of microsomal benzo(a)pyrene hydroxylase activity which appeared 1.31-fold more potent in male liver. Cytosolic N-acetyltransferase accepting sulfamethazine as substrate was about 8-fold higher in female than in male lambs. 4. The analysis of samples from various liver lobes, indicated the heterogenous distribution of microsomal proteins which is related to higher concentrations of both cytochrome b5, NADPH-cytochrome c reductase and p-nitrophenol glucuronyltransferase in left lobes.
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PMID:Comparison of hepatic drug metabolizing enzymes in three-month-old lambs and kids. 198 Aug 66

The metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, a potent bacterial mutagen and rodent carcinogen formed in low quantities in cooked meat and fish, was studied in freshly isolated rat hepatocytes. Ten metabolites were characterized by various spectroscopic methods. Sulfamate formation was the major route of metabolism in hepatocytes of untreated rats whereas ring-hydroxylated sulfuric and glucuronic acid conjugates were major metabolites in animals pretreated with the enzyme inducers Aroclor-1254, beta-naphthoflavone, or isosafrole. The formation of a mutagenic metabolite through N-oxidation, 2-(hydroxyamino)-3,8- dimethylimidazo[4,5-f]quinoxaline (HNOH-MeIQx), was an important route of metabolism in hepatocytes of pretreated animals. Its metastable derivative, the N-hydroxy-N-glucuronide, also was detected. The nitro derivative of MeIQx, a direct-acting bacterial mutagen, was readily detoxified by glutathione transferase, forming a conjugate where the thiol group of glutathione displaced the nitro moiety. Low but detectable levels of N-acetyltransferase activity were observed for MeIQx and sulfamethazine in hepatocytes. HNOH-MeIQx and 4-(hydroxyamino)biphenyl (HNOH-ABP), a recognized human carcinogen, displayed acetyl coenzyme A dependent DNA binding in hepatic cytosol assays. Sulfamethazine decreased the DNA binding of HNOH-MeIQx in hepatocytes, suggesting a competition for acetyltransferase. However, the binding of HNOH-MeIQx to DNA in hepatocytes was independent of sulfotransferase since inhibitors of this enzyme, 2,6-dichloro-4-nitrophenol (DCNP) and pentachlorophenol (PCP), did not diminish DNA binding. In contrast, binding of HNOH-ABP to DNA was not decreased by sulfamethazine, but binding was diminished by both sulfotransferase inhibitors. From these inhibition experiments it appears that a major route of binding of HNOH-MeIQx to DNA in hepatocytes is mediated through O-acetyltransferase while a significant portion of HNOH-ABP bound to DNA is catalyzed by sulfotransferase.
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PMID:The contribution of N-oxidation to the metabolism of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in rat hepatocytes. 210 23

The purpose of this investigation was to determine age-related changes of some hepatic drug-metabolizing activities in Lacaune ewes in the foetal, neonatal (1 and 4 weeks), growing (7 months), pregnant (11 months) and adult (6 years) stages. Although microsomal cytochrome P-450 was not detected in 3-month-old foetuses, it increased regularly from 1-week- to 11-month-old animals. Among mixed-function oxidases, the development of aminopyrine and ethylmorphine N-demethylases, benzo(alpha)pyrene hydroxylase and ethoxycoumarin O-deethylase were correlated to that of total cytochrome P-450. Due to their presence in foetal liver or their more rapid evolution, cytochrome b5, NADPH cytochrome c reductase, aniline hydroxylase, benzphetamine N-demethylase and erythromycin N-demethylase did not parallel the ontogenesis of cytochrome P-450. Hepatic transferases showed different developmental patterns from mono-oxygenases, so UDP glucuronyltransferase was detected in the foetus, reached maximum activity in all young ages up to the pregnant stage and subsequently fell in adult ewes. Concerning glutathione S-transferase accepting 1-chloro-2,4-dinitrobenzene as substrate, similar values were obtained in the foetus and all young animals, whereas five- to tenfold higher values were obtained in both pregnant and adult female sheep. N-acetyltransferase using sulphamethazine did not significantly change from foetuses to adults but there were large differences in the capacity of hepatic acetylation between animals belonging to the same group.
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PMID:The development of drug-metabolizing enzymes in female sheep livers. 228 26


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