Epoxide hydrolase, its function and determination of its activity in rat liver

Epoxides are a group of reactive intermediates formed by the cytochrome P-450-mediated monooxygenation of unsaturated xenobiotics. Epoxide hydrolase inactivates these epoxides by addition of water to form diols. Commonly the function of epoxide hydrolase is finally followed by excretion of the diols. However, reactivation of certain diols by a second epoxidation may happen. Epoxide hydrolase inactivates also the epoxides existing in the metabolism of endogenous compounds. The determination of the activity of epoxide hydrolase by the addition of water to styrene oxide (1,2-epoxyethylbenzene) and measurement of the concentration of the produced phenylglycol (1-phenyl-1,2-ethandiol) with subsequent separation of the 2 substances by HPLC is described. Lipophilic xenobiotics tend to accumulate into tissues, and they must be transformed to water soluble compounds to enable the excretion. In this transformation process reactive intermediates are produced. If biotransformation fails to detoxify these reactive intermediates, they may react covalently with critical targets like the genetic material, or start harmful reaction chains like lipid peroxidation. As a result of this carcinogenicity, mutagenicity etc. may ensue Miller and Miller (1976). Depending on the chemical structure of the molecule, different kinds of reactive substances are generated. Epoxides originate from oxidation of an aliphatic or aromatic double bond by the action of cytochrome P-450-mediated monooxygenases (Leibmann et al. 1979). One detoxifying pathway is the addition of water to form diols, which are of low reactivity; this reaction is catalyzed by epoxide hydrolase. Other possible pathways are the formation of glutathione conjugates or the rearrangement to aldehydes or ketones (Habig et al. 1974; Oesch 1979).(ABSTRACT TRUNCATED AT 250 WORDS)