COX1COX2

COX-1 and COX-2, also known as cyclooxygenase-1 and cyclooxygenase-2, are two isoforms of the enzyme cyclooxygenase (COX) that catalyze the rate-limiting step in prostanoid synthesis. They convert arachidonic acid to prostaglandin H2, the precursor to prostaglandins, thromboxanes, and other eicosanoids. The human genes PTGS1 and PTGS2 encode COX-1 and COX-2, respectively. Both enzymes are cytosolic homodimers located on the endoplasmic reticulum and nuclear envelope of many cell types, sharing similar catalytic activities but differing in regulation and tissue distribution.

COX-1 expression is constitutive in many tissues and supports homeostatic functions such as gastric mucosal defense, renal function, and platelet aggregation via thromboxane A2. In contrast, COX-2 is largely inducible and upregulated by inflammatory stimuli, cytokines, growth factors, and endotoxins; it also has basal expression in some tissues like the brain and kidney. Through COX-2–derived prostaglandins, especially PGE2 and PGI2, COX-2 plays a central role in pain, fever, inflammation, and neoplastic processes.

Pharmacologically, NSAIDs inhibit COX enzymes to varying degrees. Nonselective NSAIDs block both COX-1 and COX-2, providing analgesia but increasing GI risk due to COX-1 inhibition. Selective COX-2 inhibitors (coxibs) reduce inflammatory symptoms with lower GI toxicity but have been associated with cardiovascular adverse effects stemming from imbalanced prostacyclin and thromboxane production. The COX pathway remains a common target for analgesic, anti-inflammatory, and chemopreventive strategies.