Two substrates, 1-(4'-ethylphenoxy)-3,7-dimethyl-6,7-epoxy-trans-2-octene and cis-epoxymethyl stearate were used to determine the distribution of epoxide hydrase activity in mammals. The highest epoxide hydrase activity in liver subcellular fractions was found in the 100,000 g supernatant and the mitochondrial fraction, while activity in washed microsomes is lower. The 100,000 g supernatant epoxide hydrase activity is present in all organs studied. This soluble epoxide hydrase activity which is highest in the liver and kidney of mice and rabbits is also present in the duodenum, muscle, colon, lung and spleen in decreasing order of activity. The level of soluble epoxide hydrase activity, although present in all mammalian species studied, is highest in female rabbits and male mice and in comparison, significantly lower in male rats. The level of epoxide hydrase activity varies with the strain of mice used and is higher in male mice than female mice. Epoxide hydrase activity in both male and female mice increases with age particularly after mice are 5 weeks old. The soluble epoxide hydrase activity requires no cofactor and has a molecular weight of approximately 130,000 as estimated by gel filtration on Sephacryl S-200. This molecular weight is about 2.5 times that reported for the solubilized microsomal epoxide hydrase. The soluble epoxide hydrase is inhibited by inorganic ions, particularly Cu2+ and stabilized by the addition of diisopropyl fluorophosphate to the incubation mixture. Based on this data the presence of at least two epoxide hydrases in most mammalian tissues, one in the soluble fraction and the other in the microsomal fraction, is evident.
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