Biological Reactive Intermediates V: Basic Mechanistic by Daniel Mansuy, Patrick M. Dansette (auth.), Robert Snyder,

By Daniel Mansuy, Patrick M. Dansette (auth.), Robert Snyder, I. Glenn Sipes, David J. Jollow, Terrence J. Monks, James J. Kocsis, George F. Kalf, Helmut Greim, Charlotte M. Witmer (eds.)

Much of natural chemistry relies at the skill of definitely based chemical compounds to bind jointly in the course of the formation of covalent bonds. Biochemistry is replete with examination­ ples of enzymatically catalyzed reactions during which general physique parts could be associated via covalent bonds throughout the strategy of middleman metabolism. The discovering that xenobiotic chemical substances that input the physique from the surroundings, are metabolized to hugely reactive species, after which covalently react with mobile macromolecules to urge poisonous and carcinogenic results used to be an commentary that spawned the study featured within the 5th foreign Symposium on organic Reactive Intermediates (BRI V). the crowd of investigators that grew to become eager about this approach and its signifi­ cance when it comes to human well-being all started their discussions in Turku, Finland (J 975), and endured them at Guildford, England (1980), collage Park, Maryland (1985), Tucson, Arizona (1990), and Munich, Germany (1995). one of the effects have been a chain of news indexed less than, in addition to the booklet for which this serves because the Preface. • Jollow, DJ., Kocsis, J.J., Snyder, R. and Vainio, H. (eds), organic Reactive Intermediates: Formation, Toxicity and Inactivation, Plenum Press, long island, 1975. • Snyder, R., Park, D.V., Kocsis, J.J., Jollow, D.V., Gibson, G.G. and Witmer, C.M. (eds), organic Reactive Intermediates II: Chemical Mechanisms and organic results, Plenum Press, N.Y., 1982.

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Extra info for Biological Reactive Intermediates V: Basic Mechanistic Research in Toxicology and Human Risk Assessment

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With this strategy it will be possible to investigate whether the membrane topology ofxenobiotic metabolizing enzymes is important for their role in chemical carcinogenesis . • This work was supported by the Deutsche Forschungsgemeinschaft (SFB 302). t Abbreviations: ER, endoplasmic reticulum; mEH. microsomal epoxide hydrolase; omEH, truncated epoxide hydrolase; CYP/EH; cytochrome P450 I mEH fusionprotein; PAGE, polyacrylamide gel electrophoresis; PMSF, phenylmehylsulfonylfluoride. : To whom correspondence should be addressed (Present address): Biomedical Research Centre, University of Dundee, Ninewells Hospital, Dundee DD I 9SY, UK; Tel: + 44 382 632621; FAX: + 44 382 69993.

202, 677-686. 12. , Amoui M. and Levy D. (1993) Bile acid transport into hepatocyte smooth endoplasmic reticulum vesicles is mediated by microsomal epoxide hydrolase, a membrane protein exhibiting two distinct topological orientations. J Bioi Chem, 268, 20148-20155. l3. W. B. (1986) Complementary DNA and amino acid sequence of rat liver microsomal, xenobiotic epoxide hydrolase. Arch. Biochem. , 248, 121-129. 14. , Shibata M. and Ohkawa H. (1988) Genetically engineered modification of P450 monooxygenases: Functional analysis of the amino-terminal hydrophobic region and hinge region of the P4S0/reductase fused enzyme.

And Burchell B. (1990) Membrane topology of epoxide hydrolase. Biochem. Biophys. Acta, 1046, 32-39. 24 T. Friedberg et al. II. , Oesch F. and Staubli W. (1982) Immuno-electron-microscopic studies on the subcellular distribution of rat liver epoxide hydrolase and the effect of phenobarbitone and 2-acetamidofluorene treatment. Biochem. , 202, 677-686. 12. , Amoui M. and Levy D. (1993) Bile acid transport into hepatocyte smooth endoplasmic reticulum vesicles is mediated by microsomal epoxide hydrolase, a membrane protein exhibiting two distinct topological orientations.

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