PLA2s

Phospholipase A2 (PLA2) enzymes constitute a diverse superfamily that catalyzes the hydrolysis of the fatty acid at the sn-2 position of glycerophospholipids, yielding a free fatty acid and a lysophospholipid. This reaction provides precursors for eicosanoid signaling and participates in membrane remodeling, inflammation, and host defense. PLA2s are widespread across organisms and vary in localization, calcium dependence, substrate preference, and sequence.

In vertebrates, major classes include secreted PLA2 (sPLA2), which are small calcium-dependent enzymes secreted into the extracellular space; cytosolic PLA2 (cPLA2), particularly the PLA2G4 family, which preferentially liberates arachidonic acid for eicosanoid production; and calcium-independent PLA2 (iPLA2, including PLA2G6 and related groups), involved in membrane maintenance and remodeling. A separate enzyme, lipoprotein-associated PLA2 (Lp-PLA2, encoded by PLA2G7), circulates with lipoproteins and hydrolyzes oxidized phospholipids and platelet-activating factor in plasma.

PLA2 enzymes are also present in a wide range of organisms, including bacteria and venomous snakes, where venom PLA2s are studied for their enzymes’ properties and pharmacological applications.

Physiological roles include supply of arachidonic acid for prostaglandin and leukotriene synthesis, modulation of membrane properties, and intracellular signaling. Dysregulation of PLA2 activity has been associated with inflammatory conditions, cardiovascular diseases, and metabolic disorders. Inhibitors and modulators of PLA2 activity have been explored in research and therapeutic contexts, though clinical outcomes have been varied.