Prostaglandin-endoperoxide synthase (PTGS) (PTGS)

Prostaglandin-endoperoxide synthase, commonly referred to as cyclooxygenase (COX), is a membrane-bound, heme-containing bifunctional enzyme that plays a central role in the biosynthesis of prostanoids (UniProt: P23219). It catalyzes two sequential reactions: the cyclooxygenase reaction, which converts arachidonic acid to prostaglandin G2 (PGG2), and the peroxidase reaction, which reduces PGG2 to prostaglandin H2 (PGH2) (PubChem: CID 5353528). There are two primary isoforms, COX-1 and COX-2; COX-1 is constitutively expressed and maintains physiological functions such as gastric protection and platelet homeostasis, whereas COX-2 is induced by inflammatory stimuli (StatPearls: NBK547742). Inhibition of the cyclooxygenase activity by nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen is a standard approach for managing pain and inflammation. Interestingly, the peroxidase activity is considered a potential target for drugs like acetaminophen, which may act by reducing the peroxide tone required for the enzyme's activation, particularly in environments with low peroxide concentrations (PubMed: 16086638). This dual-activity enzyme is critical in various pathological processes, including chronic inflammation, fever, and the development of certain cancers. Understanding the distinct roles of the cyclooxygenase and peroxidase sites remains vital for developing safer and more effective analgesic and anti-inflammatory agents.

Other names

CyclooxygenaseCOXProstaglandin G/H synthasePGHSCyclooxygenase peroxidase activityPTGS1PTGS2

Inhibition of the cyclooxygenase active site (NSAIDs) or interference with the peroxidase activity and redox state (Acetaminophen) to prevent the synthesis of pro-inflammatory prostaglandins (StatPearls: NBK547742; PubMed: 16086638).