Search results for "epoxide hydrolase"

Role of the Well-Known Basic and Recently Discovered Acidic Glutathione S-Transferases in the Control of Genotoxic Metabolites

1991

Glutathione S-transferases (GSTs; E.C. 2. 5. 1. 18) are a family of enzymes which have increasingly attracted the interest of toxicologists, pharmacologists, biochemists and clinicians since their discovery in 1961 (1). Initially, GSTs were believed to serve as intracellular transport proteins for endogenous compounds with limited solubility in water, thus acting as an intracellular equivalent to albumin in blood plasma. In this assumed capacity of reversible binding and transport of various ligands, the corresponding protein was named ligandin (2). Following the discovery of abundant GST occurrence in most forms of aerobic life including plants, and the GST-catalysed conjugation of a wide …

Dihydrodiol Dehydrogenase: Substrate Specificity, Inducibility and Tissue Distribution

1982

The present study shows that: Dihydrodiol dehydrogenase activity is present in the 100,000 g supernatant fraction of extrahepatic tissues. Dihydrodiol dehydrogenase is able to oxidize the hydroxy group and to reduce the keto group of a number of xenobiotics including quinones derived from polycyclic aromatic hydrocarbons. Dihydrodiol dehydrogenase was not inducible by various substances including hormones, polycyclic aromatic hydrocarbons, substrates of the enzyme and potent inducers of monooxygenases, epoxide hydrolase and glutathione S-transferases. Only in the case of thyroxine was a weak induction with a high dose of the hormone observed.

Mammalian Xenobiotic Epoxide Hydrolases

2002

Fate of Epdxides

1982

One of the most important reactions of epoxides appears to be the covalent binding to DNA which can lead to mutagenicity and is strongly suspected to be the primary lesion ultimately leading to initiation of cancer (Miller and Miller, 1974; Oesch, 1973; Jerina and Daly, 1974; Sims and Grover, 1974; Heidelberger, 1975; Gelboin et al., 1972). This review first describes structure-activity relationships for the mutagenicity of some epoxides and then outlines some findings on the metabolic control of the concentration of such epoxides by a number of enzymes.

Species Differences in Enzymes Controlling Reactive Epoxides

1987

Activities of enzymes involved in the metabolic formation and catabolism of epoxides were determined in liver subcellular preparations from 11 mammalian species and various strains of mice. The most conspicuous finding was that the activities of the microsomal epoxide hydrolase were clearly lower in the mouse than in the other species. This invited the working hypothesis that epoxides may be involved in mouse liver carcinogenesis. The carcinogens may be metabolised themselves to reactive epoxides or they may modify the metabolism of epoxides formed from endogenous or other foreign compounds. To examine the former point, phenobarbital, DDT (1,1-bis(p- chlorophenyl)-2,2,2-trichloroethane), li…

Epoxide Hydrolase Isoenzymes and their Individual Contribution to the Control of Toxic Metabolites

1991

Epoxides are highly strained three membered cyclic ethers which are formed in vivo by the microsomal cytochrome P450 dependent monooxygenases as intermediates of several important biosynthetic pathways (leukotriene A4, squalene 2, 3-oxide) and as metabolites of numerous xenobiotic compounds containing olefinic or aromatic double bonds. Further transformation of these epoxides may occur by either, rearrangement to phenols, aliphatic aldehydes, or ketones; by cytochrome P450 dependent reduction to the parent compound; or by spontaneous or enzymatic conjugation to gluta-thione. Epoxides may also bind covalently to cellular nucleophiles, such as proteins and nucleic acids thus eliciting carcino…

Expression and characterization of the recombinant juvenile hormone epoxide hydrolase (JHEH) from Manduca sexta.

1998

The cDNA of the microsomal Juvenile Hormone Epoxide Hydrolase (JHEH) from Manduca sexta was expressed in vitro in the baculovirus system. In insect cell culture, the recombinant enzyme (Ms-JHEH) was produced at a high level (100 fold over background EH catalytic activity). As expected, Ms-JHEH was localized in the microsomal fraction with a molecular mass of approximately 50 kDa. Ms-JHEH showed a substrate and inhibitor spectrum similar to the wild type JHEH isolated from eggs of M. sexta. Its enzymatic activity was the highest for Juvenile Hormone III. Ms-JHEH hydrolyzed several trans-epoxides faster than cis-epoxides. A putative hydroxyl-acyl enzyme intermediate was isolated suggesting a …

Focal elevation of liver microsomal epoxide hydrolase in early preneoplastic stages and its behaviour in the further course of hepatocarcinogenesis.

1981

Abstract Treatment of rats with N-nitrosomorpholine (NNM) for 7 weeks led to a focal increase in liver microsomal epoxide hydrolase (EH) as early as 2 weeks after withdrawal of the carcinogen. This treatment also leads to hyperplastic nodules and liver tumors, but much later. At the same early time point, ATPase activity was decreased in the same islands. Most of these areas already had increased γ-glutamyltranspeptidase activity. The increase in EH at this early time point was more distinct than the decrease in ATPase which has thus far been considered a suitable marker of the earliest stages in hepatocarcinogenesis. The focal increase in EH was also observed in all benign hepatomas, but n…