Epoxide hydrolase activity in the mitochondrial fraction of mouse liver

Abstract

The intense interest in the metabolic fate of epoxidized xeno-biotics is due to several factors. For instance, epoxides are often intermediates in the lipophile to hydrophile conversions necessary for the excretion of olefinic and aromatic compounds by living systems¹, and are widely encountered in man's diet from both natural and man–made sources. Some of these epoxidized compounds may alkylate proteins and nucleic acids and thus include some of the most potent cytotoxins, mutagens and carcinogens known². In mammals, epoxides may rearrange, deoxygenate to olefins, react with glutathione to form conjugates, or be hydrolysed by water to yield 1,2–diols with or without enzymatic catalysis^1,3,4,. The enzymes which catalyse the formation of diols are known as epoxide hydrolases (EC 3.3.2.3), and their subcellular distribution is the subject of this report. Early data showed that styrene oxide hydrolase activity was associated with the microsomal subcellular fraction⁵. Epoxide hydrolase activity was subsequently demonstrated on the nuclear⁶, Golgi apparatus and plasma membranes⁷, and in the cytosol of the cell^8,9, leaving the mitochondria as the last major cellular organelle assumed to be devoid of epoxide hydrolase activity. We now report strong evidence for the occurrence of substantial epoxide hydrolase activity in the mitochondria.