Current Knowledge on Mammalian Phospholipase A(1), Brief History, Structures, Biochemical and Pathophysiological Roles

Phospholipase A(1) (PLA(1)) is an enzyme that cleaves an ester bond at the sn-1 position of glycerophospholipids, producing a free fatty acid and a lysophospholipid. PLA(1) activities have been detected both extracellularly and intracellularly, which are well conserved in higher eukaryotes, including fish and mammals. All extracellular PLA(1)s belong to the lipase family. In addition to PLA(1) activity, most mammalian extracellular PLA(1)s exhibit lipase activity to hydrolyze triacylglycerol, cleaving the fatty acid and contributing to its absorption into the intestinal tract and tissues. Some extracellular PLA(1)s exhibit PLA(1) activities specific to phosphatidic acid (PA) or phosphatidylserine (PS) and serve to produce lysophospholipid mediators such as lysophosphatidic acid (LPA) and lysophosphatidylserine (LysoPS). A high level of PLA(1) activity has been detected in the cytosol fractions, where PA-PLA(1)/DDHD1/iPLA(1) was responsible for the activity. Many homologs of PA-PLA(1) and PLA(2) have been shown to exhibit PLA(1) activity. Although much has been learned about the pathophysiological roles of PLA(1) molecules through studies of knockout mice and human genetic diseases, many questions regarding their biochemical properties, including their genuine in vivo substrate, remain elusive.