A mechanism for epoxidation of cholesterol by hepatic microsomal lipid hydroperoxides.

Evidence was obtained, using cis-stilbene as a model substrate, for the participation of peroxy and/or oxy radicals in epoxidation of cholesterol by rat liver microsomal phospholipid hydroperoxides and a ferrous ion-ADP complex. Under the conditions used, cholesterol was epoxidised to the alpha- and beta-epoxides in the ratio 1:2-4, and cis-stilbene to trans-stilbene oxide without concomitant formation of the cis-oxide. Microsomal phospholipid hydroperoxides could be replaced with methyllinoleate monohydroperoxide for the epoxidation of both substrates. The hydroperoxide-mediated epoxidations were completely inhibited by alpha-tocopherol and t-butylhydroxyanisole. A GLC study suggested that highly polyunsaturated fatty acyl constituents of the microsomal phospholipids might play an important role in epoxidation of the olefinic substrates.