de Medina_2024_Adv.Exp.Med.Biol_1440_149

Cholesterol-5,6-epoxides (5,6-ECs) are oxysterols (OS) that have been linked to several pathologies including cancers and neurodegenerative diseases. 5,6-ECs can be produced from cholesterol by several mechanisms including reactive oxygen species, lipoperoxidation, and cytochrome P450 enzymes. 5,6-ECs exist as two different diastereoisomers: 5,6alpha-EC and 5,6beta-EC with different metabolic fates. They can be produced as a mixture or as single products of epoxidation. The epoxide ring of 5,6alpha-EC and 5,6beta-EC is very stable and 5,6-ECs are prone to hydration by the cholesterol-5,6-epoxide hydrolase (ChEH) to give cholestane-3beta,5alpha,6beta-triol, which can be further oxidized into oncosterone. 5,6alpha-EC is prone to chemical and enzymatic conjugation reactions leading to bioactive compounds such as dendrogenins, highlighting the existence of a new metabolic branch on the cholesterol pathway centered on 5,6alpha-EC. We will summarize in this chapter current knowledge on this pathway which is controlled by the ChEH.