Prostaglandin-endoperoxide synthase 1 (Cyclooxygenase-1) (COX-1)

Prostaglandin-endoperoxide synthase 1 (Cyclooxygenase-1 or COX-1) is a constitutively expressed enzyme that catalyzes the rate-limiting step in the synthesis of prostanoids from arachidonic acid (UniProt P23219). In platelets, COX-1 is the sole isoform present and is responsible for producing thromboxane A2 (TXA2), a potent mediator of platelet activation, aggregation, and vasoconstriction (StatPearls, NSAIDs). Because mature platelets lack a nucleus and cannot synthesize new proteins, irreversible inhibition of COX-1 by low-dose aspirin leads to a permanent deficit in TXA2 production for the entire 7-10 day lifespan of the platelet (PubMed, PMID: 11812661). This pharmacological profile makes platelet COX-1 a critical target for the secondary prevention of arterial thrombotic events such as myocardial infarction and stroke (NIH, Aspirin). However, systemic inhibition of COX-1 also affects other tissues, most notably the gastric mucosa where it maintains protective prostaglandin levels, leading to potential side effects like gastrointestinal irritation and bleeding (DrugBank, DB00945).

Other names

PTGS1PGH synthase 1PGHS-1Prostaglandin G/H synthase 1Cyclooxygenase-1

Inhibition of the cyclooxygenase active site, preventing the conversion of arachidonic acid to prostaglandin H2 (PGH2). Aspirin specifically causes irreversible acetylation of Serine 529, while other NSAIDs act as reversible competitive inhibitors.