cyclooxygenaseen

Cyclooxygenases, commonly referred to as COX enzymes, are a family of enzymes that catalyze the first step of prostanoid biosynthesis. They convert arachidonic acid to prostaglandin G2 (PGG2), which is subsequently reduced to prostaglandin H2 (PGH2). PGH2 serves as the common precursor for various prostanoids, including prostaglandins, prostacyclin (PGI2), and thromboxane A2 (TXA2). In humans, the two main isoforms are COX-1 (PTGS1) and COX-2 (PTGS2). A third, less well characterized variant has been described in some tissues, but its clinical relevance remains uncertain.

COX-1 is generally expressed constitutively in many tissues and mediates baseline production of prostanoids that regulate normal physiological functions such as gastric mucosal protection, renal blood flow, and platelet aggregation. COX-2 is inducible and upregulated in response to inflammatory stimuli, cytokines, and growth factors, and it predominates at sites of inflammation and in certain tumors.

Mechanistically, COX enzymes possess two catalytic activities within a single active site: a cyclooxygenase reaction that converts arachidonic acid to PGG2, followed by a peroxidase reaction that reduces PGG2 to PGH2. The generated PGH2 is then converted by tissue-specific synthases into various downstream prostanoids with diverse biological effects, including modulation of inflammation, pain, fever, vascular tone, and hemostasis.

Pharmacologically, NSAIDs inhibit COX enzymes to reduce prostanoid production. Nonselective NSAIDs inhibit both COX-1 and COX-2, whereas selective COX-2 inhibitors aim to reduce inflammation with fewer gastrointestinal side effects but may carry higher cardiovascular risk. Aspirin acetylates COX-1 in platelets, diminishing TXA2 production and platelet aggregation. Genetic regulation involves the PTGS1 and PTGS2 genes encoding the respective enzymes. Cyclooxygenases thus play a central role in inflammation, homeostasis, and analgesia.

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