Cyclooxygenase-1 enzyme

The widely used platelet inhibitor aspirin or acetylsalicylic acid, by acetylating the enzyme cyclooxygenase, inhibits platelet function by preventing the formation of thromboxane A2 and the synthesis of prostaglandin I2 (PGI2) (68). Aspirin has been used in combination with other antiplatelet agents such as ticlopidine, which inhibits ADP-induced platelet aggregation (69). 

Studies in the 1970s revealed that an enzyme, cyclooxygenase (COX), converts arachidonic acid (4) to an intermediate, prostaglandin H2 (5), as shown below ... 

Competitive blocker of a-adrenergic receptors in heart and blood vessels Inhibits the enzyme HMG-CoA reductase and reduces the biosynthesis of cholesterol Acts as an angiotensin II receptor antagonist Inhibits the synthesis of prostaglandins via the selective inhibition of the enzyme cyclooxygenase-2... 

The cells in the hypothalamus that control body temperature respond to the cytokines by stimulating the activity of the membrane bound phospholipase, which results in the formation of arachidonic acid, the substrate for the enzyme cyclooxygenase-2 (COX-2) which is the rate-limiting step in the pathway for synthesis of prostaglandins. Prostaglandins influence cells in the hypothalamus that are responsible for temperature regulation. 

In Box 7.13 we saw that the widely used analgesic aspirin exerted its action by acetylating the enzyme cyclooxygenase (COX) which is involved in the production of prostaglandins. Prostaglandins are modified C20 fatty acids synthesized in animal tissues and they affect a wide variety of physiological processes, such as... 

In small doses aspirin inactivates irreversibly platelet enzyme cyclooxygenase, hence thromboxane A is not synthesised. 

Ibuprofen works by inhibiting the enzyme cyclooxygenase (COX), which in turn interferes with the synthesis of prostaglandins. COX exists as several coenzyme forms that are similar in structure COX-1, COX-2, COX-3 ibuprofen is a nonselective inhibitor of both COX-1... 

Aimer G., Guegan C., Teismann P., Naini A., Rosoklija G., Hays A. P., Chen C. P., and Przedborski S. (2001). Increased expression ofthe pro-inflammatory enzyme cyclooxygenase-2 in amyotrophic lateral sclerosis. Ann. Neurol. 49 176-185. 

After liberation, AA is converted into prostaglandin endoperoxides by the action of the enzyme cyclooxygenase. Endoperoxides are rapidly converted into either stable prostaglandins, PGE2, PGF2a, and PGD2, or thromboxane A2. AA can also be converted into lipoxygenase-dependent products such as 12-hydroperoxyeicosatetraenoic acid (12-HPETE) and 12-hydroxyeicosatet-raenoic acid (12-HETE). 

Stimulation of local prostaglandin production is possibly one protective mechanism as quercetin stimulates the enzyme cyclooxygenase and, in addition, the cyclooxygenase inhibitor, indomethacin, reverses me protective effect of quercetin on ethanol-induced ulceration. The increase in prostaglandin synthesis may explain me increase in the amount of mucus observed and its participation in ulcer prevention. Other possible mechanisms include me following ... 

Related Compounds, aspirin inhibits the synthesis of thromboxane A2 by irreversible acetylation of the enzyme cyclooxygenase. Other salicylates and nonsteroidal anti-inflammatory drugs also inhibit cyclooxygenase but have a shorter duration of inhibitory action because they cannot acetylate cyclooxygenase, ie, their action is reversible. 

Non-steroidal antiinflammatory drugs (NSAIDs) are the main therapeutic agents for the treatment of the symptoms of arthritis. The drugs seem to inhibit the enzyme cyclooxygenase and consequently the conversion of arachidoic acid into prostaglandins. The main drawbacks of NSAIDs are severe side effects, including gastrointestinal ulceration and... 

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