Phospholipase A1:: structure, distribution and function

Phospholipase (PL)A, is an enzyme that hydrolyzes phospholipids and produces 2-acyl-lysophospholipids and fatty acids. Although PLA(1) activities have been detected in many organisms and tissues, their functions have not been elucidated until recently. Currently, six extracellular and three intracellular PLA(1) enzymes are known in mammals. The extracellular PLA(1)s consist of phosphatidylserine (PS)-specific PLA, (PS-PLA(1)), membrane-associated phosphatidic acid (PA)-selective PLA(1)s (mPA-PLA(1)alpha and mPA-PLA(1)beta), hepatic lipase (HL), endothelial lipase (EL) and pancreatic lipase-related protein (PLRP)-2, all of which belong to the lipase gene family. PS-PLA1, EL, mPA-PLA(1)alpha and mPA-PLA(1)beta prefer phospholipid substrates, whereas HL and PLRP-2 show both PLA, activity and lipase activity to hydrolyze triacylglycerol. EL has a role in high-density lipoprotein (HDL) metabolism by hydrolyzing phosphatidylcholine on HDL particles, PS-PLA(1), mPA-PLA(1)alpha and mPA-PLA(1)beta have distinct structural features in two surface loops (the lid and the beta 9 loop), which are implicated in substrate recognition, PS-PLA(1), mPA-PLA(1)alpha and mPA-PLAp specifically hydrolyze PS and PA, respectively, and produce their corresponding lysophospholipids (lysophosphatidylserine and lysophosphatidic acid), which have been defined as lipid mediators with multiple biological functions. Thus, these PLA(1)s may have a physiological role in the production of these lysophospholipid mediators. The intracellular PLA(1)s consist of PA-preferring PLA(1), KIAA0725p and p125 in mammals, all of which are conserved in a wide range of organisms and have been implicated in vesicular transport.