Gamma-hydroxyalkenals are oxidatively cleaved through Michael addition of acylperoxy radicals and fragmentation of intermediate beta-hydroxyperesters.

Oxidative cleavage of arachidonate (C(20)) and linoleate (C(18)) phospholipids generates truncated C(8) or C(12) gamma-hydroxyalkenal phospholipids as well as C(5) or C(9) carboxyalkanoate phospholipids, which are abundant in atherosclerotic plaques. The gamma-hydroxyalkenals promote foam cell formation by scavenger receptor CD36-mediated endocytosis. The carboxyalkanoates are potent regulators of endothelial cell functions that may promote atherogenesis. We now report an unexpected biosynthetic interconnection; the carboxyalkanoates can be generated through oxidative cleavage of the gamma-hydroxyalkenals with the loss of three carbons. This unprecedented transformation is shown to involve Michael addition of an acylperoxy radical and fragmentation of the resulting beta-hydroxyperester.