PTGS1


 * "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 is_associated_with::enzyme that in humans is encoded by the PTGS1 is_associated_with::gene.

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

Gene and isozymes
There are two is_associated_with::isozymes of COX encoded by distinct gene products: a constitutive COX-1 (this enzyme) and an inducible is_associated_with::COX-2, which differ in their regulation of expression and tissue distribution. The expression of these two transcripts is differentially regulated by relevant is_associated_with::cytokines and is_associated_with::growth factors. A splice variant of COX-1 termed is_associated_with::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.

Function
is_associated_with::Prostaglandin-endoperoxide is_associated_with::synthase (PTGS), also known as is_associated_with::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 (is_associated_with::dioxygenase) and hydroperoxidase (is_associated_with::peroxidase) activity. The cyclooxygenase activity incorporates two oxygen molecules into arachidonic acid or alternate polyunsaturated fatty acid substrates, such as is_associated_with::linoleic acid and is_associated_with::eicosapentaenoic acid. Metabolism of is_associated_with::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 is_associated_with::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. This gene encodes COX-1, which regulates is_associated_with::angiogenesis in is_associated_with::endothelial cells. COX-1 is also involved in is_associated_with::cell signaling and maintaining tissue homeostasis.

While metabolizing arachidonic acid primarily to PGG2, COX-1 also converts this fatty acid to small amounts of a racemic mixture of is_associated_with::15-Hydroxyicosatetraenoic acids (i.e., 15-HETEs) composed of ~22% 15(R)-HETE and ~78% 15(S)-HETE is_associated_with::stereoisomers as well as a small amount of 11(R)-HETE. The two 15-HETE stereoisomers have intrinsic biological activities but, perhaps more impotantly, can be further metabolized to a major class of anti-inflammatory agents, the is_associated_with::lipoxins. In addition, PGG2 and PGH2 rearrange non-enzymatically to a mixture of is_associated_with::12-Hydroxyheptadecatrienoic acids viz.,1 2-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (i.e. 12-HHT) and 12-(S)-hydroxy-5Z,8Z,10E-heptadecatrienoic acid plus is_associated_with::Malonyldialdehyde. and can be metabolized by a is_associated_with::Cytochrome, cytochrome P4520S1 to 12-HHT (see is_associated_with::12-Hydroxyheptadecatrienoic acid). These alternate metabolites of COX-1 may contribute to its activities

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

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