On the Prevalence and Role of Addition Reactions in Lipid Peroxidation

Abstract

Plasmalogens have been reported to possess antioxidant activity; a paradoxical finding given that plasmalogens often comprise highly oxidizable polyunsaturated fatty acids esterified to the central position of the glycerol backbone. However a reasonable mechanism accounting for plasmenyl lipid activity has yet to be advanced, despite the fact that other monounsaturated lipids including cholesterol and oleate have been extensively studied. Plasmenylcholine was synthesized de novo to resolve its antioxidant activity as well as to carry out mechanistic studies to understand its basis. Autoxidation of a vinyl ether model substrate yielded a kp of 6 M-1 s-1, which affirmed it was as slower than cholesterol. However, corresponding experiments with a deuterated substrate yielded a value of 89 M-1 s-1, questioning the reliability of these studies. Our studies of plasmenyl lipid peroxidation inspired us to look into the mechanism of autoxidation of the monounsaturated lipid, oleate (using LC-MS/MS with APCI+), which was reported to proceed exclusively via H-atom transfer (HAT). Herein we have shown for the first time that oleate epoxides are formed in the autoxidation of the monounsaturated lipid.