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.
D000244:Adenosine Diphosphate; D000818:Animals; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005296:Ferrous Compounds; D008054:Lipid Peroxides / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D013267:Stilbenes / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D005296:Ferrous Compounds; D008054:Lipid Peroxides; D008563:Membrane Lipids; D010743:Phospholipids; D013267:Stilbenes; C002415:cholesterol alpha-oxide; D000244:Adenosine Diphosphate; D002784:Cholesterol