Phospholipase A2, membrane associated (PLA2)

Phospholipase A², membrane associated, refers to a family of enzymes that hydrolyze the sn‑2 acyl bond in glycerophospholipids within biological membranes. This reaction releases free fatty acids such as arachidonic acid—a precursor for pro-inflammatory eicosanoids—and lysophospholipid products. These enzymes play critical roles in cell signaling pathways related to inflammation, immune response, host defense against pathogens by disrupting microbial membranes, lipid remodeling during cellular stress or injury, and regulation of vascular tone through bioactive lipids. The superfamily includes several groups based on structure and function: secreted sPLAs² act extracellularly; cytosolic cPLAs² translocate upon activation; calcium-independent iPLAs² function without Ca²⁺; while lipoprotein-associated Lp‑PLAs² circulate bound to LDL/HDL particles. Dysregulation has been implicated in numerous diseases including chronic inflammation, cardiovascular disorders like atherosclerosis, neurodegeneration, infection susceptibility, and cancer progression. Multiple small-molecule inhibitors have been developed targeting different isoforms either at their catalytic site or allosteric regulatory regions.

Other names

PLA₂Phosphatidylcholine 2-acylhydrolaseSecretory phospholipase A₂ (sPLA₂)Cytosolic phospholipase A₂ (cPLA₂)Calcium-dependent phospholipase A₂Group IV phospholipase A₂Group IIA/V/X etc. depending on isoform

– Competitive inhibition at the active site blocking substrate access or catalysis. – Allosteric inhibition preventing conformational activation upon membrane association. – Chelation/blockade of essential cofactors such as Ca²⁺ required for activity.