Cyclooxygenase (COX) enzyme (COX (includes COX-1 and COX-2 isoforms))

Cyclooxygenases are key enzymes in the eicosanoid pathway that catalyze the conversion of arachidonic acid into prostaglandins and thromboxanes—lipid mediators involved in inflammation, pain signaling, vascular homeostasis, and other physiological processes. There are two main isoforms: **cyclooxygenase 1** (*COX‑1*) is constitutively expressed for normal physiological functions such as gastric protection and platelet aggregation; **cyclooxygenase 2** (*COX‑2*) is inducible during inflammation. Eicosapentaenoic acid (**EPA**) and docosahexaenoic acid (**DHA**)—long-chain omega‑3 polyunsaturated fatty acids—modulate this pathway by acting as alternative substrates for both COX‑1 and especially **COX‑2**, competitively inhibiting arachidonic acid metabolism. This results in reduced synthesis of pro-inflammatory prostaglandins like PGE₂ while promoting formation of less inflammatory or even anti-inflammatory lipid mediators such as resolvins and protectins[3][4]. This competitive substrate inhibition underlies many observed benefits of EPA/DHA supplementation—including reduced inflammation, improved cardiovascular outcomes, modulation of immune responses—and forms the basis for therapeutic strategies targeting these enzymes with both dietary lipids and pharmacologic agents like NSAIDs or icosapent ethyl[5][3]. The original query refers to "eicosanoid pathway modulation via competitive substrate inhibition at cyclooxygenases by EPA/DHA," which is a description of a mechanism rather than a single molecular target. The correct canonical targets here are **cyclooxygenases**, specifically *prostaglandin-endoperoxide synthase 1* (*PTGS1*, COX‑1) and *prostaglandin-endoperoxide synthase 2* (*PTGS2*, COX‑2).

Other names

Prostaglandin-endoperoxide synthasePTGSCyclooxygenase-1 (COX-1)Cyclooxygenase-2 (COX-2)PGHS

– Competitive substrate inhibition by EPA/DHA at cyclooxygenases reduces production of pro-inflammatory prostaglandins and increases anti-inflammatory/pro-resolving mediators[2][3][4]. – NSAIDs inhibit cyclooxygenases to block prostaglandin synthesis.