PTGS1

PTGS1

Prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase)
PDB rendering based on 1diy.
Available structures
PDB Ortholog search: RCSB
Identifiers
1.14.99.1
RNA expression pattern
"COX-1" redirects here. COX-1 may also refer to mitochondrial cytochrome c oxidase subunit 1 (cox1).

Cyclooxygenase-1 (COX-1), also known as prostaglandin G/H synthase 1, prostaglandin-endoperoxide synthase 1 or prostaglandin H2 synthase 1, is an enzyme that in humans is encoded by the PTGS1 gene.[1][2]

History

Cyclooxygenase (COX) is the central enzyme in the biosynthetic pathway to prostaglandins from arachidonic acid. This protein was purified more than 20 years ago and cloned in 1988.[3][4]

Gene and isozymes

There are two isozymes of COX encoded by distinct gene products: a constitutive COX-1 (this enzyme) and an inducible COX-2, which differ in their regulation of expression and tissue distribution. The expression of these two transcripts is differentially regulated by relevant cytokines and growth factors.[5] A splice variant of COX-1 termed COX-3 was identified in the CNS of dogs, but does not result in a functional protein in humans. Two smaller COX-1-derived proteins (the partial COX-1 proteins PCOX-1A and PCOX-1B) have also been discovered, but their precise roles are yet to be described.[6]

Function

Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase (COX), is the key enzyme in prostaglandin biosynthesis. It converts free arachidonic acid, released from membrane phospholipids at the sn-2 ester binding site by the enzymatic activity of phospholipase A2, to prostaglandin (PG) H2. The reaction involves both cyclooxygenase (dioxygenase) and hydroperoxidase (peroxidase) activity. The cyclooxygenase activity incorporates two oxygen molecules into arachidonic acid or alternate polyunsaturated fatty acid substrates, such as linoleic acid and eicosapentaenoic acid. Metabolism of arachidonic acid forms a labile intermediate peroxide, PGG2, which is reduced to the corresponding alcohol, PGH2, by the enzyme’s hydroperoxidase activity. There are two isozymes of COX encoded by distinct gene products: a constitutive COX-1 (this enzyme) and an inducible COX-2, which differ in their regulation of expression and tissue distribution. (A splice variant of COX-1, initially termed COX-3 was identified in the CNS of dogs, but does not result in a functional protein in humans.) This gene encodes COX-1, which regulates angiogenesis in endothelial cells. COX-1 is also involved in cell signaling and maintaining tissue homeostasis.

COX-1 promotes the production of the natural mucus lining that protects the inner stomach and contribute to reduced acid secretion and reduced pepsin content.[7][8] COX-1 is normally present in a variety of areas of the body, including not only the stomach but any site of inflammation.[9][7]

Clinical significance

COX-1 is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin. TXA2, the major product of COX-1 in platelets, induces platelet aggregation.[10][11] Research has shown that the inhibition of COX-1 is sufficient to explain why aspirin is effective at reducing cardiac events.

See also

References

Further reading