Stafforini_2015_Enzymes_38_71

This chapter is focused on the plasma form of PAF-acetylhydrolase (PAF-AH), a lipoprotein-bound, calcium-independent phospholipase A2 activity also referred to as lipoprotein-associated phospholipase A2 and PLA2G7. PAF-AH catalyzes the removal of the acyl group at the sn-2 position of PAF and truncated phospholipids generated in settings of inflammation and oxidant stress. Here, I discuss current knowledge related to the structural features of this enzyme, including the molecular basis for association with lipoproteins and susceptibility to oxidative inactivation. The circulating form of PAF-AH is constitutively active and its expression is upregulated by mediators of inflammation at the transcriptional level. Several new mechanisms of regulation have been identified in recent years, including effects mediated by PPARs, VEGFR, and the state of cellular differentiation. Moreover, I discuss recent studies describing significant variations in the structure and regulation of PAF-AH from diverse species, which is likely to have important implications for the function of this enzyme in vivo.