Cyclooxygenase-1, Cyclooxygenase-2, and Cyclooxygenase-3 (COX-1, COX-2, COX-3)

Cyclooxygenase enzymes, officially known as prostaglandin-endoperoxide synthases (PTGS), catalyze the conversion of arachidonic acid to prostaglandin H₂, a precursor of prostanoids such as prostaglandins, thromboxane, and prostacyclin. COX-1 is constitutively expressed in most tissues where it maintains physiological functions (e.g., gastric protection, platelet function), while COX-2 is inducible and upregulated primarily in inflammation, pain, and cancer. Both enzymes are membrane-bound homodimers with highly homologous three-dimensional structures, featuring distinct domains for membrane binding and catalytic activity. Pharmaceutical inhibition of these enzymes underlies the action of NSAIDs, which alleviate pain and inflammation but can produce notable side effects depending on the isoform targeted. The status of COX-3 as a functional enzyme is not supported in humans; it likely reflects alternative splicing found in other species[1][2][3][4][5][6][7][8].

Other names

PTGS1Prostaglandin G/H synthase 1Prostaglandin-endoperoxide synthase 1PHSPESPTGS2Prostaglandin G/H synthase 2Prostaglandin-endoperoxide synthase 2Often refers to an alternative splicing product of PTGS1 seen in some animals; not recognized as a functional enzyme in humans

Competitive inhibition of the cyclooxygenase active site (NSAIDs); Irreversible inhibition by acetylation (aspirin); Selective inhibition of COX-2 isoform (COXIBs, e.g., celecoxib); Possible central inhibition via splice variants (paracetamol)