Prostaglandin biosynthesis pathway

The prostaglandin biosynthesis pathway is a fundamental metabolic cascade that produces bioactive lipid mediators known as prostanoids, which include prostaglandins, prostacyclin, and thromboxanes (PubMed: 15655524). The process begins with the release of arachidonic acid from membrane phospholipids by phospholipase A2, followed by the action of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) to form the unstable intermediate prostaglandin H2 (StatPearls: NBK499831). Various terminal synthases then convert PGH2 into specific tissue-dependent prostanoids that regulate a wide array of physiological functions including gastric mucosal protection, renal hemodynamics, and vascular tone (NIH: PMC3081099). In pathological states, an over-activation of this pathway, particularly via the inducible COX-2 enzyme, leads to the excessive production of Prostaglandin E2 (PGE2), a major mediator of inflammation, fever, and pain sensitization (PubMed: 25777443). Consequently, this pathway is one of the most clinically significant therapeutic targets, addressed primarily by nonsteroidal anti-inflammatory drugs (NSAIDs). While effective at reducing inflammation and pain, long-term inhibition of the pathway can lead to serious adverse effects, such as gastrointestinal bleeding or cardiovascular events, due to the suppression of physiologically protective prostanoids (PubChem: CID 5280360).

Other names

Prostanoid biosynthesis pathwayCyclooxygenase pathwayArachidonic acid metabolism (cyclooxygenase branch)Prostaglandin metabolic process

Drugs primarily target this pathway by inhibiting the cyclooxygenase enzymes (COX-1 and COX-2), which are responsible for converting arachidonic acid into prostaglandin H2 (PGH2). By blocking these enzymes, drugs reduce the production of downstream prostanoids such as PGE2 and TXA2, which mediate pain, fever, and inflammatory responses (StatPearls: NBK499831; PubMed: 11723464).