Phospholipase A2 enzymes in eicosanoid generation

Phospholipase A(2) (PLA(2)) enzymes cleave esterified fatty acids from membrane glycerophospholipids. The 20-carbon polyunsaturated fatty acid, arachidonic acid, is used as substrate by intermediate enzymes For the generation of eicosanoids, including leukotrienes and prostanoid products. An expanding number of PLA(2) enzymes has now been identified that may participate in arachidonic acid release and thus serve a rate-limiting role in eicosanoid biosynthesis. Cellular PLA(2) function for various members is regulated by constitutive or elicited expression, as well as by posttranslational events such as phosphorylation. In addition, the function of some cellular PLA(2) enzymes is regulated by a requirement for calcium or by localization to a particular subcellular compartment. Finally, some PLA(2) enzymes are secreted from the cell where they may directly interact with plasma membrane or transmembrane receptors to function as autocrine or paracrine mediators. Evaluating the roles of a number of these functionally similar PLA(2) enzymes in the biosynthesis of leukotrienes and other eicosanoids is the focus of this review.