This chapter discusses the formation and measurement of cholesterol epoxides. The isomeric cholesterol (1) 5,6-epoxides 5,6α-epoxy-5α-cholestan-3β-ol (cholesterol α-oxide, 1) and (2) 5,6β-epoxy-5β-cholestan-3β-ol (cholesterol β-oxide, 2) are found in human tissues and foods and on bioassay exhibit diverse toxic effects in vitro. Both are formed together from cholesterol (cholest-5-en-3β-ol, 3) by many defined oxidants, including air oxidation, and by the actions of soybean lipoxygenases and of liver microsomal lipid peroxidation systems in vitro. Of all the recognized oxidation products of cholesterol formed by attack on cholesterol of defined active oxygen species, the 5,6-epoxides (1 and 2) are the most broadly formed, being formed by ground state dioxygen (3O2), electronically excited (singlet) dioxygen (1O2), peroxide (O22+), ozone (O3), dioxygen cation (O2+), and hydroxyl radical (HO·). The ratio of product 5,6-epoxides (1:2) favors the 5β,6β-epoxide in most cases, the 5α,6α-epoxide predominating only in oxidations involving the specific 5α,6α-epoxidase, HO·, and peracids. In new experimental systems generating the 5,6-epoxides, it is of importance that the products be properly identified and the 5,6-epoxide ratio (1:2) ascertained. The 5α,6α epoxide alone has been posed as the 5,6-epoxide formed in biological systems and as the active agent in numerous bioassays but without adequate supporting evidence.
ASJC Scopus subject areas
- Molecular Biology