cyclooxygenase

Cyclooxygenase (COX) refers to a family of enzymes that catalyze the rate-limiting step in prostanoid biosynthesis, converting arachidonic acid to prostaglandin G2 (PGG2) and then to prostaglandin H2 (PGH2). PGH2 is the common substrate for a suite of synthases that generate prostaglandins, thromboxanes, and prostacyclin, which regulate inflammation, pain, fever, hemostasis, renal function, and vascular tone.

In humans, the two principal isoforms are COX-1 and COX-2. COX-1 is typically expressed constitutively in many tissues and supports homeostatic functions such as protecting the gastric mucosa, maintaining renal blood flow, and facilitating platelet aggregation. COX-2 is inducible and upregulated during inflammation; it contributes to inflammatory pain and fever, although it is also expressed at lower levels in some tissues for normal physiological roles.

Biochemically, COX enzymes are homodimeric, membrane-bound proteins associated with the endoplasmic reticulum and, in some contexts, the nuclear envelope. Each monomer contains a cyclooxygenase domain and a peroxidase domain and requires a heme prosthetic group for activity.

Inhibition of COX activity underpins the mechanism of nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin irreversibly acetylates COX-1 and COX-2, while many other NSAIDs inhibit COX reversibly. Selective COX-2 inhibitors were developed to reduce gastrointestinal toxicity but have been linked to cardiovascular risks. The balance of COX-1– and COX-2–derived prostanoids influences bleeding, gastric protection, inflammation, and thrombosis.