Cholesterol hydroperoxides and their degradation mechanism.

Cholesterol is one of the oxidizable lipids constituting biomembranes and plasma lipoproteins. Cholesterol hydroperoxides (Chol-OOH) are the primary products if cholesterol is subjected to attack by reactive oxygen species. In particular, singlet molecular oxygen reacts with cholesterol to yield cholesterol 5α-hydroperoxide as the major hydroperoxide species. Chol-OOH may accumulate in biological systems because of its resistance to glutathione-dependent enzymatic detoxification reactions. Their degradation products (including hydroxycholesterol and 7-ketocholesterol) participate in the pathophysiological functions of oxysterols. Highly reactive cholesterol 5,6-secosterol present in atherosclerotic lesions can be derived from the degradation of cholesterol 5α-hydroperoxide. Chol-OOH themselves may affect the lipid rafts of biomembranes, thereby leading to the modification of signal transduction pathways.