Figure. Arachidonic acid metabolism and generation of eicosanoids. Phospholipase A₂ (PLA₂) catalyzes phosphatidyl choline into arachidonic acid when an agonist stimulates a G-protein-coupled receptor on the cell surface. Arachidonic acid is the key molecule for generation of lipid mediators of inflammation. Prostanoids (prostaglandins, thromboxanes) and prostacyclins are produced through cyclooxygenase (COX) activity, while leukotrienes are generated by the action of 5-lipoxygenase (LO). The lipoxygenase:lipoxygenase (LO:LO) pathway—activity of a combination of two LO, 5, 12, or 15 on the same arachidonic acid molecule—produces lipoxins. Aspirin can trigger the production of epimeric lipoxins through acetylation of COX-2, yielding 15-epi-H(p)ETEs, which are then converted to lipoxins by transcellular biosynthesis using 5-LO from neutrophils.