Fig. 2.
Major pathways for the biosynthesis of eicosanoids in platelets. Arachidonic acid (AA), esterified in membrane phospholipids, can be released upon platelet activation by different stimuli via the action of phospholipases (PLs), including the cytosolic phospholipase A2 (cPLA2). In platelets, AA is transformed to PGH2 by the activity of COX-1; then, PGH2 is the substrate of different synthases, thus leading to the formation of the prostanoids: TXA2, PGE2, PGD2, PGF2α. Thromboxane synthase (TXAS), cytosolic PGE synthase (cPGES), microsomal PGE synthase-2 (mPGES-2), lipocalin-type prostaglandin D synthase (L-PGDS), hematopoietic prostaglandin D synthase (H-PGDS) and PGF synthase (PGFS) are the downstream synthases involved in the production of prostanoids. AA is also transformed to 12(S)-HETE by the activity of p12-LOX. The enzyme produces 12(S)-hydroperoxy-eicosatetraenoic acid [12(S)-HPETE] which is, then, converted to 12(S)-HETE by glutathione reductase (GR). PGE2, PGD2 and 12(S)-HETE can be esterified into membrane phospholipids by the action of fatty acid CoA ligase (FACL) to produce new lipid mediators, i.e., the phospholipid esterified eicosanoids