Abstract

Human liver microsomal epoxide hydrolase was purified to apparent homogeneity as judged by a single protein-staining band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Sheep antibody to human liver epoxide hydrolase reacted with the enzyme in detergent-solubilized human liver microsomes, giving a single immunoprecipitin band which formed a line of identity with the pure human enzyme. Antibody against the human enzyme reacted well with epoxide hydrolase in detergent-solubilized monkey liver microsomes by the Ouchterlony test but less strongly cross-reacted with the enzyme from rat liver and several other species. The antibody produced against purified human liver epoxide hydrolase precipitated the enzyme but did not inhibit catalytic activity, reminiscent of the relationship of rat liver epoxide hydrolase to its antibody. The absolute level of epoxide hydrolase in liver microsomal samples from 11 human subjects, as measured by a radial immunodiffusion assay, varied 3.4-fold whereas the rate of hydration of octene oxide varied 2.9-fold. The excellent correlation of the amounts of epoxide hydrolase determined catalytically or immunochemically (r = 0.99) indicated that interindividual variation in octene oxide hydration rates by human liver microsomes is a consequence of differences in amount of epoxide hydrolase protein which is present, and not the result of differences in levels of endogenous modulators of catalytic activity.