PLA2enzymen

PLA2 enzymes, short for phospholipase A2 enzymes, are a diverse family of hydrolases that cleave the sn-2 ester bond of glycerophospholipids. The hydrolysis releases a free fatty acid, often arachidonic acid, and a lysophospholipid. This reaction provides substrates for the production of lipid mediators such as prostaglandins, thromboxanes, and leukotrienes, and also participates in membrane remodeling and signaling.

Classification among animals covers several major groups. Secreted PLA2s (sPLA2) are small, calcium-dependent enzymes released into extracellular spaces or the secretory pathway; they include several vertebrate groups and many venom PLA2s with toxic effects. Cytosolic PLA2s (cPLA2) are larger, intracellular enzymes that typically require calcium and show preference for arachidonic acid release, linking directly to eicosanoid biosynthesis. Calcium-independent PLA2s (iPLA2) function without Ca2+ and contribute to membrane homeostasis, remodeling, and lipid signaling.

Mechanistically, many PLA2 enzymes use a catalytic dyad or triad that includes a histidine residue and an aspartate residue, with a calcium-binding loop in secreted forms that coordinates Ca2+. The precise active-site configuration varies by class but converges on efficient hydrolysis of the phospholipid sn-2 bond.

Physiological and clinical relevance is broad. In mammals, cPLA2s regulate inflammatory and immune responses through arachidonic acid release, while sPLA2s participate in host defense and lipid turnover. Venom PLA2s are potent toxins that disrupt cell membranes. Pharmacological inhibitors of PLA2 activity have been explored for inflammatory and cardiovascular diseases, with mixed clinical outcomes and ongoing research into selective targeting.

See also: phospholipase A2, arachidonic acid, eicosanoids.