Formation and metabolism in vitro of 5,6-epoxides of cholesterol and β-sitosterol

Abstract

The formation of 5α,6α- and 5β,6β-epoxides of cholesterol and β-sitosterol in rat liver subcellular fractions has been studied. The results show that the epoxidation seems to occur only in connection with the nonspecific tissue oxidation of the sterols. The β-epoxides were formed in three- to fourfold excess over the α-epoxides. Both cholesterol epoxides were efficiently converted by a microsomal hydrolase into the 3β,5α,6β-triol. The conversion was less extensive with β-sitosterol epoxides, especially the β-epoxide. The possible biological significance in the formation of the sterol epoxides and the triols was evaluated by their ability to inhibit the microsomal cholesterol 7α-hydroxylase. Only the cholesterol epoxides and especially the β-epoxide were active in this respect.

Keywords

• lipid peroxidation
• epoxide hydrolase
• cholestane-3β,5α,6β-triol
• cholesterol-7α-hydroxylase
• inhibition by 5,6-epoxysterols and 3β,5α,6β-trihydroxysterols
• hydroxyalkylated Sephadex LH-20