Authors: Arand, Michael
Cronin, Annette
Hengstler, Jan G.
Herrero Plana, Maria Elena
Lohmann, Matthias
Oesch, Franz
Title: Detoxification Strategy of Epoxide Hydrolase
Other Titles: The Basis for a Threshold in Chemical Carcinogenesis
Language (ISO): en
Abstract: The human microsomal epoxide hydrolase, a single enzyme, has to detoxify a broad range of structurally diverse, potentially genotoxic epoxides that are formed in the course of xenobiotic metabolism. The enzyme has developed a unique strategy to combine a broad substrate specificity with a high detoxification efficacy, by immediately trapping the reactive compounds as covalent intermediates and by being expressed at high levels for high trapping capacity. Computer simulation and experimental data as well as existing epidemiologic studies reveal this detoxification strategy as the mechanistic basis for a threshold in the tumorigenesis of mutagenic carcinogens.
Subject Headings: computer simulation
enzyme kinetics
genotoxic
mechanism
structure
URI: http://hdl.handle.net/2003/25628
http://dx.doi.org/10.17877/DE290R-117
Issue Date: 2003-03-13
Appears in Collections:Original Articles

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