Cyclooxygenase (COX) pathway (COX pathway)

The cyclooxygenase (COX) or prostaglandin pathway is a central metabolic cascade that converts arachidonic acid into bioactive prostanoids, including prostaglandins, prostacyclin, and thromboxanes (StatPearls, 2023). This pathway is primarily governed by two enzymes: COX-1, which maintains physiological homeostasis such as gastric mucosal integrity and platelet function, and COX-2, which is rapidly induced by inflammatory stimuli (Nature Reviews Drug Discovery, 2003). Dysregulation of the COX pathway is fundamentally linked to the pathogenesis of inflammation, pain, and fever, and has been implicated in the development of colorectal cancer and cardiovascular disorders (PubMed, 2017). Therapeutic targeting of this pathway is achieved through nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, which alleviate symptoms by reducing the production of pro-inflammatory prostaglandins (NIH, 2022). These drugs work by binding to the active site of COX enzymes, thereby preventing the oxygenation of arachidonic acid. However, the clinical use of these agents is often limited by side effects, including gastrointestinal toxicity associated with COX-1 inhibition and increased cardiovascular risk associated with COX-2 selectivity (Journal of the American College of Cardiology, 2018). Understanding the balance between these isoforms is crucial for developing safer anti-inflammatory therapies. The pathway also serves as a target for low-dose aspirin in the prevention of secondary cardiovascular events due to its irreversible inhibition of platelet COX-1.

Other names

Arachidonic acid cascadeProstanoid biosynthetic pathwayProstaglandin-endoperoxide synthase pathwayCOX-1/COX-2 pathway

Inhibition of cyclooxygenase enzymes (COX-1 and COX-2), preventing the conversion of arachidonic acid to prostaglandin H2 (PGH2), which is the common precursor for all prostanoids including prostaglandins, prostacyclin, and thromboxanes.