Epoxide hydrolase (E.C. 3.3 2.3), a detoxifier enzyme of humans, plays a crucial role in biotransformation of epoxides. Epoxides are major chemical carcinogens of the vertebrate animals. It is a metabolite of xenobiotics resulting from the action of cytochrome P-450 on xenobiotics. Epoxide hydrolase catalyzes the hydration of epoxides at either the aromatic or olefinic double bonds. Epoxide hydrolase is localized in the smooth endoplasmic microsomal fraction of the liver of most vertebrates and in the cytoplasmic domain. The molecular weight ranges from 49,000 daltons to 59,000 daltons. Multiple forms of epoxide hydrolase have been purified in several laboratories. Some of these forms include two microsomal forms, epoxide hydrolase I and II with molecular weight of 49,000 and 59,000 daltons respectively. The cytosolic form is also 59,000 daltons. These forms show distinct substrate specificities and immunological differences. Many unanswered questions about the structure of the different forms of epoxide hydrolase still remain. Some of these unanswered questions include whether these forms are synthesized from the same gene transcripts or different genes. Using oligonucleotides and cDNA complementary to epoxide hydrolase mRNA as probes, it will be possible to identify and clone all the genes for the different forms of this enzyme. The use of Southern blot and in situ hybridization techniques, will lead to the identification and purification of the different forms of the gene(s). The purified genes will be sequenced. It is anticipated that the information obtained from the sequence analysis of the DNA will account for the differences in amino acid sequence of each form which might have resulted in the differences in their molecular weights.
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