Search results for "Epoxide"
showing 10 items of 251 documents
Studies on the Biosynthesis of Microsomal Membrane Proteins. Site of Synthesis and Mode of Insertion of Cytochrome b5, Cytochrome b5 Reductase, Cytoc…
1982
The site of synthesis and mechanism of insertion into membranes of several microsomal polypeptides was studied using translation system programmed in vitro with polysomes or with mRNA extracted from free and membrane-bound rat liver polysomes. Primary translation products of cytochrome b5, NADH: cytochrome b5 oxidoreductase, NADPH: cytochrome P-450 oxidoreductase and epoxide hydrolase were isolated by specific immunoprecipitation and compared with the mature proteins. The following observations were made: 1 While cytochrome b5 and NADH: cytochrome b5 oxidoreductase are synthesized in free polysomes, NADPH: cytochrome P-450 oxidoreductase and epoxide hydrolase are made in membrane-bound poly…
Endogenous role of epoxide-hydratase. Development of a steroid epoxide-hydratase assay and properties of the enzyme.
1979
A highly sensitive and rapid radiometric assay for the determination of specific epoxide hydratase activity with a steroid epoxide (16α, 17α-epoxy-1,3,5(10)-estratrien-3-ol, ‘estroxide’) has been developed. The unreacted substrate was separated from the product 1,3,5(10)-estratrien-3,16β,17α-triol by extraction into light petroleum. The product was then extracted into ethyl acetate and measured by scintillation spectrometry. Radiochromatography established that after subtraction of the blank the entire radioactivity measured in the ethyl acetate phase resulted from the product 1,3,5(10)-estratrien-3,16,17-triol, whilst high performance liquid chromatography with the four possible isomers of…
The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase
2003
The mammalian soluble epoxide hydrolase (sEH) is an enzyme with multiple functions, being implicated in detoxification of xenobiotic epoxides as well as in regulation of physiological processes such as blood pressure. The enzyme is a homodimer, in which each subunit is composed of two domains. The 35-kDa C-terminal domain has an α/β hydrolase fold and harbors the catalytic center for the EH activity. The 25-kDa N-terminal domain has a different α/β fold and belongs to the haloacid dehalogenase superfamily of enzymes. The catalytic properties of the enzyme reported so far can all be explained by the action of the C-terminal domain alone. The function of the N-terminal domain, other than in …
Effects of desipramine and alprazolam in the forced swim test in rats after long-lasting termination of chronic exposure to picrotoxin and pentylenet…
1993
Abstract Rats were treated for 5 weeks with three subconvulsant doses of picrotoxin (PTX) and pentylenetetrazol (PTZ) per week to induce a persistent reduction of the GABA A receptor function which results in chemical kindling. Fifteen days after termination of this treatment schedule, the effect of desipramine (DMI) and alpraxolam (ALP) on immobility time in the forced swim test (FST) was evaluated. Chronic PTX and PTZ did not alter the immobility time. Acute PTX and PTZ reduced the immobility of rats chronically treated with vehicle but not of those exposed chronically to PTX and PTZ. Chronic PTX did not influence the anti-immobility effect of DMI, but blocked that of ALP. Chronic PTZ mar…
Use of monoclonal and polyclonal antibodies as structural and topographical probes for hepatic epoxide hydrolase
1983
AbstractMonoclonal antibodies have been prepared against rat liver epoxide hydrolase (EH), some of which gave precipitation lines on immunodiffusion against pure EH suggesting the presence of repetitive structural domains on the enzyme. Using ELISA, with polyclonal antibodies to rat and rabbit liver EH, reactivity and therefore structural similarities between EH of all species tested, including human, were observed. This was in contrast to immunodiffusion results demonstrating the limitations of the latter technique. Using monoclonal antibodies in ELISA, greatest structural similarity was between rat, mouse, and Syrian hamster EH and relatively little between rat and human. Two of the antib…
Mechanism-based predictions of interactions.
1994
Abstract Exposure to more than one toxic compound is common in real life. The resulting toxic effects are often more than the simple sum of the effects of the individual compounds. It is unlikely that it will ever be possible to test all combinations. It is therefore highly desirable to improve or develop means for reasonably approximating predictions of interactions. In order to be valid and extrapolatable, these predictions are most promising if they are mechanism-based. Examples will be given for possibilities of mechanism-based predictions of interactions which exceed trivialities of simple increases by enzyme induction of enzymatic rates of a given biotransformation pathway leading to …
Species differences in activating and inactivating enzymes related to the control of mutagenic metabolites
1977
Microsomal monooxygenases catalyze the biosynthesis of epoxides from olefinic and aromatic compounds whilst microsomal epoxide hydratase and cytoplasmic glutathione S-transferases are responsible for their further biotransformation. Although catalytically very efficient the cytoplasmic glutathione S-transferases play, due to their subcellular localization, a minor role in the inactivation of epoxides derived from large lipophilic compounds and were, therefore, not included in this study. It was shown with such a lipophilic compound, benzo(a)pyrene, as a model substance and with liver enzyme mediated bacterial mutagenesis as biological endpoint that species and strain differences in epoxide …
Antimutagenic activity of organosulfur compounds from Allium is associated with phase II enzyme induction
2001
In a previous study, we showed that naturally occurring organosulfur compounds (OSCs) from garlic and onion modulated the activation of carcinogen via the alteration of cytochromes P450. The present study was undertaken to determine the incidence of the in vivo induction of phase II enzymes by individual OSCs on the genotoxicity of several carcinogens. Diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS), were administered by gavage (1mmol/kg) to male SPF Wistar rats for 4 consecutive days. The effects of treatments on phase II enzymes and on the genotoxicity of carcinogens were evaluated with hepatic cytosols and microsomes from OSCs-treated…
cis- and trans-1,2-diphenylaziridines: induction of xenobiotic-metabolizing enzymes in rat liver and mutagenicity in Salmonella typhimurium.
1986
trans-Stilbene imine (trans-1,2-diphenylaziridine) is the nitrogen analog of trans-stilbene oxide, a potent inducer of several microsomal and cytosolic xenobiotic-metabolizing enzymes. Although the acute toxicity of cis- and trans-stilbene imines prevents their application at the usual dose for trans-stilbene oxide (400 mg/kg/day), it is apparent that the imines nevertheless potently induce several xenobiotic-metabolizing enzymes in rat liver. The IP administration of trans-stilbene imine resulted in statistically significant increases in the activities of aminopyrine N-demethylase, microsomal epoxide hydrolase, glutathione transferase (toward 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nit…
Microsomal Biotransformation of Benzo[ghi]perylene, a Mutagenic Polycyclic Aromatic Hydrocarbon without a “Classic” Bay Region
2005
Carcinogenic polycyclic aromatic hydrocarbons (PAH), e.g., benzo[a]pyrene (BaP), possess a bay region comprising an ortho-fused benzene ring. Benzo[ghi]perylene (BghiP) represents the group of PAHs lacking such a "classic" bay region and hence cannot be metabolically converted like BaP to bay region dihydrodiol epoxides considered as ultimate mutagenic and carcinogenic metabolites of PAH. BghiP exhibits bacterial mutagenicity in strains TA98 (1.3 his(+)-revertant colonies/nmol) and TA100 (4.3 his(+)-revertant colonies/nmol) of Salmonella typhimurium after metabolic activation by the postmitochondrial hepatic fraction of CD rats treated with 3-methylcholanthrene. Inhibition of microsomal epo…