Prostaglandin-endoperoxide synthase (COX) (COX)

The arachidonic acid cyclooxygenase pathway is a central biochemical route responsible for the biosynthesis of prostanoids, which include prostaglandins, thromboxanes, and prostacyclin (StatPearls, "NSAIDs", 2023). This pathway is primarily governed by two enzyme isoforms, Prostaglandin-endoperoxide synthase 1 (COX-1) and Prostaglandin-endoperoxide synthase 2 (COX-2), which catalyze the conversion of arachidonic acid into prostaglandin H2 (UniProt, P23219, P35354). COX-1 is constitutively expressed and maintains essential homeostatic functions such as gastric mucosal integrity and platelet aggregation, while COX-2 is an inducible enzyme primarily associated with the mediation of inflammation, fever, and pain (PubMed, PMID: 11591437). This pathway is the primary therapeutic target for non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (NIH, "Arachidonic Acid Metabolism"). While effective for treating chronic inflammatory conditions and pain, pharmacological inhibition of this pathway carries risks, including gastrointestinal toxicity and adverse cardiovascular events due to the disruption of the prostanoid balance (PubMed, PMID: 12185250). Additionally, the pathway plays a significant role in oncogenesis, particularly in the development and progression of colorectal cancer (PubMed, PMID: 15507612).

Other names

CyclooxygenaseArachidonate cyclooxygenasePTGSArachidonic acid cyclooxygenase pathwayProstaglandin H2 synthaseProstaglandin G/H synthase

Inhibition of the cyclooxygenase active site (COX-1 and/or COX-2), preventing the oxygenation of arachidonic acid to prostaglandin G2 and subsequent reduction to prostaglandin H2, thereby limiting the production of pro-inflammatory and homeostatic prostanoids.