Biosynthesis of plasmalogens in mammalian cells and their accelerated catabolism during cellular activation

Plasmalogens are specialized phospholipids which have a unique conformation, possess distinct molecular dynamics, and serve as the major endogenous phospholipid storage depot for arachidonic acid in many mammalian cells. Recently, several novel intracellular phospholipases A₂ have been identified which selectively hydrolyze plasmalogen substrate. Quantitative analysis of phospholipid molecular species in several cell types demonstrate that plasmalogen molecular species containing arachidonic acid are selectively hydrolyzed during cell stimulation and serve as the major source of arachidonic acid mass released during cellular activation. Collectively, these results underscore the importance of plasmalogen hydrolysis as a major mechanism for the release of eicosanoid metabolites during agonist stimulation. Accordingly, this chapter will review recent insights on the de novo synthesis of plasmalogens, address the molecular mechanisms responsible for the enrichment of arachidonic acid in plasmalogen molecular species and, finally, will focus on the mechanisms which mediate accelerated plasmalogen catabolism and the release of arachidonic acid during cellular activation.