Origin,metabolism, and adverse health effects of cholesterol oxidation products

Cholesterol oxidation products (COP), also called oxysterols, enter the organism by intake of COP-containing foodstuff or are generated in vivo by enzymatic or non-enzymatic oxidation (peroxidation) of cholesterol. COP are transported in lymph and blood with lipoproteins (mainly fatty acyl monoesters at the 3β-position) or bound to albumin. As being substrates for acyl CoA: cholesterol acyltransferase (ACAT), lecithin:cholesterol acyltransferase (LCAT), and cholesteryl ester transfer protein (CETP), COP are esterified and exchanged between lipoproteins and are distributed in the whole organism. Kupffer cells and hepatocytes are the target cells for COP transformation and excretion via bile secretion. Regarding biological activities, COP reveal widespread effects on cholesterol metabolism as well as on structure and function of cellular membranes. Throughout their actions, COP were shown to be cytotoxic but they were also suggested to be regulatory agents. Their detrimental part in atherogenesis seems to be still underestimated, while valid data on the role of COP in carcinogenesis are still missing.