Cyclooxygenase-1 and Cyclooxygenase-2 enzymes (COX-1 and COX-2)

Cyclooxygenase-1 and Cyclooxygenase-2 are enzymes responsible for the initial committed step in the biosynthesis of prostanoids, including prostaglandins and thromboxanes, from arachidonic acid. COX-1 is constitutively expressed and primarily involved in normal homeostatic functions such as gastric mucosal protection and platelet aggregation. In contrast, COX-2 is inducible by inflammatory stimuli, growth factors, or cytokines, and is involved in pathological processes including inflammation, pain, fever, and tumorigenesis. Both are homodimers comprising an epidermal growth factor-like domain, a membrane binding domain that interacts with the lipid bilayer, and a catalytic domain with cyclooxygenase and peroxidase active sites. The enzymes are therapeutic targets for nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit COX activity to alleviate pain and inflammation. Selectivity between isoforms is clinically important for balancing efficacy and side-effect profiles, notably gastrointestinal protection versus cardiovascular risk. COX-2 overexpression is a marker and therapeutic target in many cancers.

Other names

Prostaglandin-endoperoxide synthase 1 (PTGS1)Prostaglandin-endoperoxide synthase 2 (PTGS2)Prostaglandin G/H synthaseCyclooxygenase-1 (COX-1)Cyclooxygenase-2 (COX-2)Prostanoid synthaseProstaglandin synthase (PHS)Prostaglandin synthetase (PHS)Prostaglandin-endoperoxide synthetase (PES)

Reversible or irreversible inhibition of cyclooxygenase (COX) active site, thus blocking conversion of arachidonic acid to prostaglandins and thromboxanes Selective inhibition (COX-2 inhibitors/coxibs for anti-inflammatory action but sparing gastric protection) Acetylation (aspirin irreversibly acetylates a serine residue in the active site)