Cytosolic phospholipase A2 alpha (cPLA2α) (cPLA2α)

Cytosolic phospholipase A2 alpha (cPLA2α) is a critical enzyme in the inflammatory response, responsible for the hydrolysis of membrane phospholipids to release arachidonic acid (UniProt: P47712). This release is the rate-limiting step in the production of pro-inflammatory eicosanoids, such as prostaglandins and leukotrienes. The C2 domain of cPLA2α is a 120-amino acid regulatory domain that mediates the enzyme's translocation from the cytosol to intracellular membranes in response to elevated calcium levels (PubMed: 10734107). This membrane binding is essential for the enzyme to access its substrate and exert its catalytic activity. Due to its central role in initiating inflammation, cPLA2α is a major therapeutic target for conditions like rheumatoid arthritis, asthma, and cardiovascular disease (PubMed: 15548708). Pharmacological strategies include the development of small-molecule inhibitors that either block the catalytic site or specifically target the C2 domain to prevent membrane translocation (PubMed: 22411015). Inhibiting this enzyme offers a broader anti-inflammatory effect compared to downstream inhibitors like NSAIDs, though it presents challenges regarding homeostatic lipid balance (PubMed: 18416573).

Other names

Cytosolic phospholipase A2 alpha C2 domainPLA2G4AGroup IVA phospholipase A2cPLA2-alphaPhospholipase A2 group IVACalcium-dependent phospholipid-binding protein

Inhibition of arachidonic acid release by blocking the enzyme's catalytic site or preventing its calcium-dependent membrane translocation via the C2 domain (PubMed: 22411015).