Cyclo

Cyclooxygenase (COX), also known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for the formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin, and thromboxane. These molecules are critical for various physiological functions such as inflammation, pain, fever regulation, and blood clotting. There are two main isoforms of the enzyme: COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and is involved in the maintenance of normal physiological functions, while COX-2 is inducible and mainly expressed in cells at sites of inflammation.

Function

Cyclooxygenase catalyzes the conversion of arachidonic acid, a fatty acid released from the cell membrane phospholipids, to prostaglandin H2 (PGH2), the precursor of other prostanoids. This reaction involves two steps: the cyclooxygenase activity, which introduces two oxygen molecules into arachidonic acid to form a cyclic endoperoxide, and the peroxidase activity, which reduces the endoperoxide to PGH2. The prostanoids produced by the action of COX have diverse roles in the body, including modulation of inflammation, pain perception, regulation of blood flow in the kidneys, and maintenance of a protective lining in the stomach.

Isoforms

COX-1

COX-1 is expressed constitutively in many tissues, including the stomach, kidneys, and platelets. It is involved in the production of prostanoids that regulate normal cellular processes, such as gastric protection, platelet aggregation, and vascular homeostasis.

COX-2

COX-2 is an inducible enzyme that is expressed in response to inflammatory stimuli, such as cytokines, growth factors, and tumor promoters. It is primarily found in macrophages, monocytes, and other cells involved in inflammation. The prostanoids produced by COX-2 are important mediators of inflammation and pain.

Inhibition

Inhibition of cyclooxygenase is a common mechanism of action for non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, ibuprofen, and naproxen. These drugs can reduce inflammation, pain, and fever by blocking the production of prostanoids. Selective COX-2 inhibitors, also known as COX-2 selective NSAIDs or coxibs, were developed to reduce gastrointestinal side effects associated with non-selective NSAID use by specifically inhibiting COX-2 activity.

Clinical Significance

Alterations in COX activity have been implicated in various diseases. Overexpression of COX-2 has been observed in several types of cancer, suggesting a role in tumorigenesis. Additionally, COX-2 inhibitors have been studied for their potential anti-cancer properties. The role of COX enzymes in cardiovascular diseases is complex, as inhibition of COX-2 can reduce the risk of colon cancer but may increase the risk of heart attack and stroke.

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