Prostaglandin H synthase (PGHS)

Prostaglandin H synthase (PGHS) is a bifunctional enzyme that catalyzes the rate-limiting step in prostaglandin biosynthesis. It exists in two main isoforms: PGHS-1 (COX-1) and PGHS-2 (COX-2). COX-1 is constitutively expressed in most cells and is responsible for housekeeping functions, while COX-2 is primarily induced by inflammatory stimuli. The enzyme contains both cyclooxygenase and peroxidase activities. The cyclooxygenase activity incorporates two oxygen molecules into arachidonic acid (released from membrane phospholipids by phospholipase A2) to form prostaglandin G2 (PGG2). The peroxidase activity then reduces PGG2 to prostaglandin H2 (PGH2). PGH2 serves as the common precursor for various bioactive prostanoids, including prostaglandins (PGD2, PGE2, PGF2α), prostacyclin (PGI2), and thromboxane A2 (TXA2). These prostanoids act on specific G protein-coupled receptors to mediate diverse physiological and pathophysiological processes. Prostaglandins regulate numerous biological functions, including vascular tone, platelet aggregation, gastric mucosal protection, uterine contraction, and inflammatory responses. In the vascular system, prostacyclin (PGI2) promotes vasodilation and inhibits platelet aggregation, while thromboxane A2 causes vasoconstriction and promotes platelet aggregation. PGHS is the primary target of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit the enzyme's activity and thereby reduce prostaglandin synthesis. This mechanism underlies the analgesic, antipyretic, and anti-inflammatory effects of these widely used medications.

Other names

Cyclooxygenase (COX)Prostaglandin G/H synthaseProstaglandin endoperoxide synthasePTGS

Dual enzyme activity: cyclooxygenase and peroxidase functions. Converts arachidonic acid to prostaglandin G2 (PGG2) via cyclooxygenase activity. Reduces PGG2 to prostaglandin H2 (PGH2) via peroxidase activity. PGH2 serves as the precursor for various prostaglandins and thromboxanes.