Platelet-activating factor acetylhydrolases: An overview and update

Platelet-activating factor acetylhydrolases (PAF-AHs) are unique members of the phospholipase A2 family that can hydrolyze the acetyl group of PAF, a signaling phospholipid that has roles in diverse (patho)physiological processes. Three types of PAF-AH have been identified in mammals, one plasma type and two intracellular types [PAF-AH (I) and PAF-AH (II)]. Plasma PAF-AH and PAF-AH (II) are monomeric enzymes that are structurally similar, while PAF-AH (I) is a multimeric enzyme with no homology to other PAF-AHs. PAF-AH (I) shows a strong preference for an acetyl group, whereas plasma PAF-AH and PAF-AH (II) also hydrolyze phospholipids with oxidatively modified fatty acids. Plasma PAF-AH has been implicated in several diseases including cardiovascular disease. PAF-AH (I) is required for spermatogenesis and is increasingly recognized as an oncogenic factor. PAF-AH (II) was recently shown to act as a bioactive lipid-producing enzyme in mast cells and thus could be a drug target for allergic diseases. This article is part of a Special Issue entitled Novel functions of phospholipase A2 Guest Editors: Makoto Murakami and Gerard Lambeau.