Cholesterol Autoxidation Revisited: Debunking the Dogma Associated with the Most Vilified of Lipids

摘要

The longstanding dogma that cholesterol (chol) autoxidation gives chol 7-hydroperoxide (7-OOH) as the sole primary product is shown to be invalid. In fact, the epimers of each of chol 4-OOH, 6-OOH, and 7-OOH are readily formed. Although the C4-H bond that must be cleaved to produce the chol 4-OOH and 6-OOH products is significantly stronger than the C7-H bond, H-atom abstraction from C4 is facilitated by H-bond formation between the attacking peroxyl radical and the 3β-OH. Chol 5α-OOH is also formed, but only in the presence of a good H-atom donor. Chol 5α-OOH and 6-OOH undergo Hock fragmentation to yield the secosterols implicated in cardiovascular and neurodegenerative diseases, suggesting that they are likely to arise simply from autoxidation and not from reactions with O_3 or ~1O_2.