Pathways of cholesterol oxidation via non-enzymatic mechanisms

Cholesterol has many functions, including those that affect biophysical properties of membranes, and is a precursor to hormone synthesis. These actions are governed by enzymatic pathways that modify the sterol nucleus or the isooctyl tail. The addition of oxygen to the cholesterol backbone produces its derivatives known as oxysterols. In addition to having an enzymatic origin, oxysterols can be formed in the absence of enzymatic catalysis in a pathway usually termed “autoxidation,” which has been known for almost a century and observed under various experimental conditions. Autoxidation of cholesterol can occur through reactions initiated by free radical species, such as those arising from the superoxide/hydrogen peroxide/hydroxyl radical system and by non-radical highly reactive oxygen species such as singlet oxygen, HOCl, and ozone. The susceptibility of cholesterol to non-enzymatic oxidation has raised considerable interest in the function of oxysterols as biological effectors and potential biomarkers for the non-invasive study of oxidative stress in vivo.

• Cholesterol has many functions.
• Addition of oxygen into the cholesterol backbone produces derivatives known as oxysterols.
• Oxysterols are produced by enzymatic mechanisms or by autoxidation.
• Autoxidation of cholesterol occurs via free radical or non-radical pathways.