Diverse Functions of Secretory Phospholipases A₂

Phospholipase A 2 enzymes (PLA 2 s) catalyze the hydrolysis of glycerophospholipids at their sn-2 position releasing free fatty acids and lysophospholipids. Mammalian PLA 2 s are classified into several categories of which important groups include secreted PLA 2 s (sPLA 2 s) and cytosolic PLA 2 s (cPLA 2 s) that are calcium-dependent for their catalytic activity and calcium-independent cytosolic PLA 2 s (iPLA 2 s). Platelet-activating factor acetylhydrolases (PAF-AHs), lysosomal PLA 2 s, and adipose-specific PLA 2 also belong to the class of PLA 2 s. Generally, cPLA 2 enzymes are believed to play a major role in the metabolism of arachidonic acid, the iPLA 2 family to membrane homeostasis and energy metabolism, and the sPLA 2 family to various biological processes. The focus of this review is on recent research developments in the sPLA 2 field. sPLA 2 s are secreted enzymes with low molecular weight (with the exception of GIII sPLA 2 ), Ca 2+ -requiring enzymes with a His-Asp catalytic dyad. Ten enzymatically active sPLA 2 s and one devoid of enzymatic activity have been identified in mammals. Some of these sPLA 2 s are potent in arachidonic acid release from cellular phospholipids for the biosynthesis of eicosanoids, especially during inflammation. Individual sPLA 2 enzymes exhibit unique tissue and cellular localizations and specific enzymatic properties, suggesting their distinct biological roles. Recent studies indicate that sPLA 2 s are involved in diverse pathophysiological functions and for most part act nonredundantly.