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Chemico-Biological Interactions 150 (2004) 149159 Functional analysis of human microsomal epoxide hydrolase

Summary: Chemico-Biological Interactions 150 (2004) 149­159
Functional analysis of human microsomal epoxide hydrolase
genetic variants
Vinayak P. Hosagraharaa,1, Allan E. Rettieb, Christopher Hassettc,
Curtis J. Omiecinskic,
a Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA
b Department of Medicinal Chemistry, University of Washington, Seattle, WA 98105, USA
c Center for Molecular Toxicology, 115 Henning, The Pennsylvania State University, University Park, PA 16802, USA
Received 14 June 2004; received in revised form 30 July 2004; accepted 30 July 2004
Human microsomal epoxide hydrolase (EPHX1) is active in the metabolism of many potentially carcinogenic or otherwise
genotoxic epoxides, such as those derived from the oxidation of polyaromatic hydrocarbons. EPHX1 is polymorphic and
encodes allelic variation at least two amino acid positions, Y113H and H139R. In a number of recent molecular epidemiological
investigations, EPHX1 polymorphism has been suggested as a susceptibility factor for several human diseases. To better evaluate
the functional contribution of EPHX1 genetic polymorphism, we characterized the enzymatic properties associated with each
of the respective variant proteins. Enzymatic profiles were evaluated with cis-stilbene oxide (cSO) and benzo[a]pyrene-4,5-
epoxide (BaPO), two prototypical substrates for the hydrolase. In one series of experiments, activities of recombinant EPHX1
proteins were analyzed subsequent to their expression using the pFastbac®
baculovirus vector in Spodoptera frugiperda-9 (Sf9)
insect cells, and purification by column chromatography. In parallel studies, EPHX1 activities were evaluated with human liver


Source: Andrews, Anne M. - Huck Institutes of the Life Sciences, Pennsylvania State University
Omiecinski, Curtis - Department of Veterinary and Biomedical Sciences, Pennsylvania State University


Collections: Biology and Medicine