Cyclooxygenase ( COX), officially known as prostaglandin-endoperoxide synthase ( PTGS), is an enzyme (specifically, a family of , ) that is responsible for biosynthesis of , including thromboxane and such as prostacyclin, from arachidonic acid. A member of the animal-type heme peroxidase family, it is also known as prostaglandin G/H synthase. The specific reaction catalyzed is the conversion from arachidonic acid to prostaglandin H2 via a short-lived prostaglandin G2 intermediate.
Pharmaceutical inhibition of COX can provide relief from the symptoms of inflammation and pain. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, exert their effects through inhibition of COX. Those that are specific to the COX-2 isozyme are called COX-2 inhibitors. The active metabolite (AM404) of paracetamol is a COX inhibitor, a fact to which some or all of its Analgesic has been attributed.
In medicine, the root symbol "COX" is encountered more often than "PTGS". In genetics, "PTGS" is officially used for this family of and because the root symbol "COX" was already used for the cytochrome c oxidase family. Thus, the two isozymes found in humans, PTGS1 and PTGS2, are frequently called COX-1 and COX-2 in medical literature. The names "prostaglandin synthase (PHS)", "prostaglandin synthetase (PHS)", and "prostaglandin-endoperoxide synthetase (PES)" are older terms still sometimes used to refer to COX.
Biology
Pharmacology
Classical NSAIDs
The classical COX inhibitors are not selective and inhibit all types of COX. The resulting inhibition of prostaglandin and thromboxane synthesis has the effect of reduced inflammation, as well as antipyretic, antithrombotic and analgesic effects. The most frequent adverse effect of NSAIDs is irritation of the gastric mucosa as prostaglandins normally have a protective role in the gastrointestinal tract. Some NSAIDs are also acidic which may cause additional damage to the gastrointestinal tract.
Newer NSAIDs
Natural COX inhibition
A variety of have been found to inhibit COX-2.
Fish oils provide alternative fatty acids to arachidonic acid. These acids can be turned into some anti-inflammatory prostacyclins by COX instead of pro-inflammatory prostaglandins.
Hyperforin has been shown to inhibit COX-1 around 3-18 times as much as aspirin.
Calcitriol (vitamin D) significantly inhibits the expression of the COX-2 gene.
Caution should be exercised in combining low dose aspirin with COX-2 inhibitors due to potential increased damage to the gastric mucosa. COX-2 is upregulated when COX-1 is suppressed with aspirin, which is thought to be important in enhancing mucosal defense mechanisms and lessening the erosion by aspirin.
Cardiovascular side-effects of COX inhibitors
This evidence, however, has been contradicted by the 2016 PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen) trial of 24,081 participants, which shows a lower incidence of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke for Celecoxib as compared to both Naproxen and Ibuprofen.
Fish oils (e.g., cod liver oil) have been proposed as a reasonable alternative for the treatment of rheumatoid arthritis and other conditions as a consequence of the fact that they provide less cardiovascular risk than other treatments including NSAIDs.
Effects of COX on the immune system
See also
- Cyclooxygenase-1
- Cyclooxygenase-2
- Cyclooxygenase-3 (not functional in humans)
- Discovery and development of COX-2 selective inhibitors
External links
- GONUTS Page: Cyclooxygenase
- Cyclooxygenase: Proteopedia, life in 3D
- A discussion of the enzymatic mechanism, including interactive 3D models
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