Eicosanoid synthesis pathway enzymes involved in platelet aggregation

The eicosanoid synthesis pathway in platelets is a critical enzymatic cascade that converts membrane-derived arachidonic acid into potent bioactive lipids, primarily thromboxane A2 (TXA2), which drives platelet activation and aggregation (StatPearls, 2025; Creative Proteomics, 2020). The process begins with the release of arachidonic acid by cytosolic phospholipase A2 (cPLA2), followed by its conversion to prostaglandin H2 (PGH2) by cyclooxygenase-1 (COX-1), and finally to TXA2 by thromboxane synthase (TXAS) (NIH, 2024; Pharmacy180, 2025). TXA2 acts as an autocrine and paracrine signal, binding to thromboxane receptors (TP) to amplify platelet responses and promote vasoconstriction (Wikipedia, 2025; NIH, 2021). This pathway is the primary target for antiplatelet therapy, most notably through the use of low-dose aspirin, which irreversibly inhibits COX-1 to prevent thrombotic events (NIH, 2021; StatPearls, 2025). Dysregulation of this pathway is central to the pathogenesis of cardiovascular diseases such as myocardial infarction and stroke, making these enzymes vital therapeutic targets (Wikipedia, 2025; Creative Proteomics, 2020).

Other names

Platelet eicosanoid synthesis pathwayArachidonic acid cascade in plateletsProstaglandin-endoperoxide synthase 1 (COX-1)Thromboxane-A synthase (TBXAS1)Cytosolic phospholipase A2 (cPLA2)Arachidonate 12-lipoxygenase (12-LOX)COX-1/TXAS pathway

Inhibition of key enzymes in the eicosanoid cascade, primarily the irreversible acetylation of COX-1 by aspirin to block thromboxane A2 production, or the inhibition of thromboxane synthase to prevent the conversion of PGH2 to TXA2.