Abstract
Two modifiers of microsomal epoxide hydrase activity, metyrapone and cyclohexene oxide, are shown to exert differential effects on the catalytic activity of the purified enzyme from rat liver. The effects of these modifiers on rates of metabolism are dependent on the substrate studied. Metyrapone (6 mM) increases the rate of hydration of octene 1,2-oxide and benzo[a]anthracene 5,6-oxide by 210% and 40%, respectively, does not affect the rate of benzo[a]pyrene 4,5-oxide metabolism, and inhibits the rate of benzo[a]pyrene 11,12-oxide and dibenzo[a,h]-anthracene 5,6-oxide hydration by approximately 60%. At low concentrations (60-120 µM), cyclohexene oxide has no effect on the rate of metabolism of octene 1,2-oxide or benzo[a]anthracene 5,6-oxide, inhibits the rate of hydration of benzo[a]pyrene 4,5-oxide by 40%, and inhibits the rate of benzo[a]pyrene 11,12-oxide and dibenzo[a,h]-anthracene 5,6-oxide metabolism by 80%. Cyclohexene oxide is a competitive inhibitor of the metabolism of octene 1,2-oxide and is a noncompetitive inhibitor of benzo[a]pyrene 11,12-oxide metabolism. Anti-rat epoxide hydrase gamma globulin produced in goat, sheep, donkey, and rabbit forms an immunoprecipitate with rat liver epoxide hydrase but the immunoprecipitated enzyme retains full catalytic activity. Antibody produced in the goat appears to differentiate two sets of antigenic determinants in the rat enzyme. Antibody against rat liver epoxide hydrase does not cross-react with microsomal preparations of the enzyme from rabbit or human liver and shows poor cross-reactivity with guinea pig and hamster liver epoxide hydrase. These results indicate the presence of different forms of hepatic epoxide hydrase in several species and suggest that rat liver microsomal epoxide hydrase contains multiple regulatory sites. However, the possible existence of more than one form of the enzyme in rat liver cannot be excluded at the present time.
- Copyright © 1978 by Academic Press, Inc.
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