Plasmalogens: Their metabolism and central role in the production of lipid mediators

Considerable interest in plasmalogens has recently been rekindled because of their important linkage to the production of potent bioactive lipid mediators such as platelet-activating factor (PAF) and the various oxygenated metabolites of arachidonic acid. Moreover, much progress has been made towards attaining a better understanding of the metabolism and functional role of plasmalogens in mammalian cells, including the establishment of the direct metabolic relationship between the ethanolamine- and choline-containing plasmalogens. This chapter reviews the early studies that established the enzymatic reactions leading to the synthesis of the ethanolamine plasmalogens by a Δl-alkyl desaturase and discusses more recent results that have shown the O-alk-1-enyl linkage in choline plasmalogens can be derived from the ethanolamine plasmalogens by enzymatic reactions involving the remodeling of substituents at both the sn-2 and/or n-3 positions. Other topics covered include a critical discussion of criteria and methods required for establishing proof of the plasmalogenic structure isolated from biological materials and an updated view of how plasmalogens participate in the trafficking of arachidonate among membrane phospholipids. A number of studies suggest the ethanolamine plasmalogens serve as a repository for arachidonate and other polyunsaturates in that they appear to be the final destination in the movement of polyenoic acids through the choline and ethanolamine-containing subclasses of glycerophospholipids. Ethanolamine-containing lysoplasmalogens have been shown to be involved in the biosynthesis of PAF by serving as acyl acceptors for the arachidonoyl moiety from alkylarachidonoyl-glycerophosphocholine (a membrane precursor of PAF) in a reaction catalyzed by a CoA-independent transacylase. The lyso-PAF intermediate formed by the transacylase can then be acetylated to form PAF by an acetyl-CoA acetyltransferase. The coupled phospholipase A 2 /transacylase pathway also is closely associated with the production of eicosanoid mediators since arachidonic acid and other polyenoic fatty acids are released from the ethanolamine plasmalogens in the initial hydrolytic step that forms the lyso plasmalogen acceptor.