Phospholipase A2 (PLA2) (PLA2)

The arachidonic acid release machinery refers to the enzymatic system, predominantly centered on the Phospholipase A2 (PLA2) family, responsible for liberating arachidonic acid from the sn-2 position of membrane phospholipids (UniProt P47712). Cytosolic phospholipase A2 (cPLA2) is the primary isoform involved in this process during inflammatory signaling, activated by increases in intracellular calcium and phosphorylation by MAP kinases (PubMed PMID: 21532552). Once released, arachidonic acid acts as the rate-limiting precursor for the eicosanoid pathway, leading to the production of prostaglandins, leukotrienes, and thromboxanes (StatPearls, Arachidonic Acid Metabolism). This machinery is a critical focal point in the inflammatory response, making it a major target for anti-inflammatory therapy. Glucocorticoids are the most well-known class of drugs that modulate this system, primarily by inducing the expression of annexins (lipocortins) which inhibit PLA2 activity (PubMed PMID: 15914678). While direct inhibitors of PLA2 isoforms like varespladib and darapladib have been developed, achieving clinical success has been difficult due to the complex redundancy and physiological roles of different PLA2 enzymes in cellular homeostasis.

Other names

cPLA2Cytosolic phospholipase A2PLA2G4APhosphatidylcholine 2-acylhydrolaseArachidonyl-specific phospholipase A2sPLA2Secretory phospholipase A2

Inhibition of the enzymatic hydrolysis of membrane phospholipids at the sn-2 position, preventing the liberation of arachidonic acid and subsequent production of pro-inflammatory eicosanoids.