Search results for "Microsomal epoxide hydrolase"

Stereochemical features of the hydrolysis of 9,10-epoxystearic acid catalysed by plant and mammalian epoxide hydrolases

2002

cis-9,10-Epoxystearic acid was used as a tool to probe the active sites of epoxide hydrolases (EHs) of mammalian and plant origin. We have compared the stereochemical features of the hydrolysis of this substrate catalysed by soluble and membrane-bound rat liver EHs, by soluble EH (purified to apparent homogeneity) obtained from maize seedlings or celeriac roots, and by recombinant soybean EH expressed in yeast. Plant EHs were found to differ in their enantioselectivity, i.e. their ability to discriminate between the two enantiomers of 9,10-epoxystearic acid. For example, while the maize enzyme hydrated both enantiomers at the same rate, the EH from soybean exhibited very high enantioselecti…

Human liver cytosolic epoxide hydrolases.

1988

Human liver epoxide hydrolases were characterized by several criteria and a cytosolic cis-stilbene oxide hydrolase (cEHcso) was purified to apparent homogeneity. Styrene oxide and five phenylmethyloxiranes were tested as substrates for human liver epoxide hydrolases. With microsomes activity was highest with trans-2-methylstyrene oxide, followed by styrene 7, 8-oxide, cis-2-With methylstyrene oxide, cis-1,2-dimethylstyrene oxide, trans-1, 2-dimethylstyrene oxide and 2, 2-dimethylstyrene oxide. With cytosol the same order was obtained for the first three substrates, whereas activity with 2, 2-dimethylstyrene oxide was higher than with cis-1,2-dimethylstyrene oxide and no hydrolysis occurred …

Studies on the importance of microsomal epoxide hydrolase in the detoxification of arene oxides using the heterologous expression of the enzyme in ma…

1994

In order to investigate the role of the microsomal epoxide hydrolase (mEH) in the detoxification of arene oxides in the presence of a high endogenous glutathione S-transferase (GST) activity-a situation found in several organs--we expressed the rat mEH cDNA in BHK21 Syrian hamster cells. These cells have high GST activities but contain an extremely low endogenous mEH enzyme activity. We obtained several cell clones which expressed the mEH heterologously, as determined by immunoblotting. The cell clone BHK21-mEH/Mz1 had the highest level of mEH protein. Immunofluorescence showed that the level of expression was almost homogeneous throughout the cell population. Total protein isolated from th…

Genotoxicity characteristics of reverse diol-epoxides of chrysene.

2017

Trans-3,4-dihydroxy-3,4-dihydrochrysene (chrysene-3,4-diol), a major metabolite of chrysene, is further metabolized by rat liver enzymes to products which effectively revert the his- Salmonella typhimurium strain TA98 to histidine prototrophy, but are only weakly mutagenic in strain TA100 and in Chinese hamster V79 cells (acquisition of resistance to 6-thioguanine). The liver enzyme mediated mutagenicity of chrysene-3,4-diol is substantially enhanced in the presence of 1,1,1-trichloropropene 2,3-oxide, an inhibitor of microsomal epoxide hydrolase. The predominant metabolites of chrysene-3,4-diol, namely the anti- and syn-isomers of its 1,2-oxide (termed reverse diol-epoxides), proved to be …

Isoenzyme-specific phosphorylation of cytochromes P-450 and other drug metabolizing enzymes.

1987

Abstract A series of fourteen cytochrome P-450 isoenzymes was treated with three different protein kinases and found to devide into isoenzymes phosphorylated (i) by both the cyclic AMP-dependent kinase and the calcium-phospholipid-dependent kinase (P-450 PB 3a and PB 2e), (ii) by none of these kinases (P-450 PB 1b, MC 1b, UT 1, and thromboxane synthase), and (iii) by either the cyclic AMP-dependent kinase (P-450 LM 2, PB 2d, and PB 3b) or the calcium-phospholipid-dependent kinase (P-450 PB 1a, PB 2a, MC 1a, LM 3c, and LM 4). Other components of the monooxygenase system, cytochrome P-450 reductase, cytochrome b5, cytochrome b5 reductase as well as microsomal epoxide hydrolase, were poor subs…

An insect juvenile hormone-specific epoxide hydrolase is related to vertebrate microsomal epoxide hydrolases.

1996

Abstract We describe the first cDNA sequence encoding a juvenile hormone-specific epoxide hydrolase from an insect. A full-length cDNA clone revealed a 462-amino-acid open reading frame encoding an amino acid sequence with 44% identity and 64% similarity to human microsomal epoxide hydrolase. All residues in the catalytic triad (residues Asp 227 -His 428 -Asp 350 in the M. sexta protein) were present, as was the conserved Trp 154 corresponding to the oxyanion hole. The surprising similarity of insect juvenile hormone epoxide hydrolase to vertebrate microsomal epoxide hydrolases, coupled with the ancient lineage of the epoxide hydrolases and haloalkane dehalogenases, suggests that this catab…

Mechanisms of Toxification and Detoxification which Challenge Drug Candidates and Drugs

2007

Almost all drugs are metabolized in the human organism. In most cases this changes the toxicity, sometimes by toxification, sometimes by detoxification. For obvious ethical reasons, the toxicity cannot be experimentally studied in human beings. In systems available for toxicity studies such as whole animals or human or animal cells in culture, the drug metabolism is substantially different from that in the human organism. Risk assessment for human therefore requires knowledge of drug metabolism, its differences between systems, and the consequences for toxicity. In phase 1 of drug metabolism (oxidoreductions and hydrolyses) drugs are often toxified. This is especially the case if the result…

‘Threshold effect’ of increasing tocopherol ingestion upon the microsomal epoxide hydrolase activity of rat liver

1990

Specificity of mouse liver cytosolic epoxide hydrolase for K-region epoxides derived from polycyclic aromatic hydrocarbons

1980

Mouse liver cytosol epoxide hydrolase, known to be very active for certain alkene oxides, had a specific activity which was 2.1-, 11- and 160-fold lower than that of the microsomal epoxide hydrolase for the arene oxides 7-methylbenz[a]anthracene 5,6-oxide, benz[a]anthracene 5,6-oxide and phenanthrene 9,10-oxide, respectively. For benzo[a]pyrene 4,5-oxide no activity (less than 10 pmol product/mg protein/min) of cytoplasmic epoxide hydrolase was detectable. The specific activity of cytoplasmic epoxide hydrolase was much lower for all K-region epoxides investigated, compared to trans-stilbene oxide used as a positive control and for which a new assay is described. It is concluded from these r…

Evidence for Several Hepatic Proteins Related to Microsomal Epoxide Hydrolase

1989

Epoxide hydrolases catalyze the conversion of epoxides, some of which have been shown to be carcinogenic, to dihydrodiols (Guenthner and Oesch 1981). At least three forms of epoxide hydrolases exist in rats, two of which, namely mEHb and mEHch, are associated mainly with the microsomal fraction (Oesch et al 1984; Levin et al 1983) whereas one form namely cEH is found to a large extent in the cytosolic fraction (Gill and Hammock 1981). These three forms differ in their immunological and catalytic properties quite considerably (Guenthner et al 1981). In the case of mEHb the existence of several closely related isoenzymes with an identical apparent subunit molecular weight (Mrs) of 50,000 was …