γ-Hydroxyalkenals Are Oxidatively Cleaved through Michael Addition of Acylperoxy Radicals and Fragmentation of Intermediate β-Hydroxyperesters

摘要

Oxidative cleavage of arachidonate (C_(20)) and linoleate (C_(18)) phospholipids generates truncated C_8 or C_(12) γ-hydroxyalkenal phospholipids as well as C_5 or C_9 carboxyalkanoate phospholipids, which are abundant in atherosclerotic plaques. The γ-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 γ-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 β-hydroxyperester.