6533b7d4fe1ef96bd1263498

RESEARCH PRODUCT

Purification of rat liver epoxide hydratase to apparent homogeneity.

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description

Epoxide hydratase (EC 4.2.1.63) is a microsomal enzyme which catalyses the conversion of epoxides to trans-dihydrodiols. Epoxides, produced by the action of microsomal monooxygenases (EC 1.14.1.1) from aromatic and olefinic compounds, are thought to be responsible for many of the harinful effects of polycyclic hydrocarbons and related compounds. Thus epoxide hydratase, together with glutathione 9transferases, (EC 2.5.1.18) may play an important role in the removal of carcinogenic and cytotoxic metabolites (for reviews see [l-3]). It has been reported [4,5] that dihydrodiols formed from some polycyclic hydrocarbons (benz(a)anthracene and benzo(a)pyrene) are reactivated by the microsomal monooxygenases to dihydrodiol epoxides which may represent ultimate carcinogens. If this is the case epoxide hydratase could play a critical role being responsible both for forming the proximate carcinogen and removing the ultimate carcinogen. Indeed an inverse correlation between susceptibility to carcinogenesis by polycyclic hydrocarbons and inducibility of epoxide hydratase by the same agents at different developmental stages of the same animal species has been observed [6], A thorough knowledge of the properties of the enzymes involved in the metabolic activation and inactivation processes is essential for an understanding of the mechanisms of cytotoxicity and carcinogenesis by polycyclic hydrocarbons. Many research groups have studied the monooxygenases and several have recently reported a purification of cytochromes I’450 and ph4s [7-91. However, although many inhibitors, activators, and inducers of epoxide hydratase exhibiting various degrees of specificity are known [2] , pure