"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

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 that in humans is encoded by the PTGS1 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

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.

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 cytokine

Cytokine

Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

s and growth factor

Growth factor

A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....

s. A splice variant of COX-1 termed COX-3

COX-3

COX-3 is an enzyme that is encoded by the PTGS1 gene, but is not functional in humans. COX-3 is the third and most recently discovered cyclooxygenase isozyme, the others being COX-1 and COX-2...

 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

Prostaglandin

Prostaglandin

A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....

-endoperoxide synthase

Synthase

In biochemistry, a synthase is an enzyme that catalyses a synthesis process.Following the EC number classification, they belong to the group of ligases, with lyases catalysing the reverse reaction....

 (PTGS), also known as cyclooxygenase

Cyclooxygenase

Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...

 (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

Dioxygenase

In molecular biology, a dioxygenase is an enzyme which catalyses the incorporation of both atoms of molecular oxygen into substrates using a variety of reaction mechanisms. Cleavage of aromatic rings is one of the most important functions of dioxygenases, which play key roles in the degradation of...

) and hydroperoxidase (peroxidase

Peroxidase

Peroxidases are a large family of enzymes that typically catalyze a reaction of the form:For many of these enzymes the optimal substrate is hydrogen peroxide, but others are more active with organic hydroperoxides such as lipid peroxides...

) activity. The cyclooxygenase activity incorporates two oxygen molecules into arachidonic acid or alternate polyunsaturated fatty acid substrates, such as linoleic acid

Linoleic acid

Linoleic acid is an unsaturated n-6 fatty acid. It is a colorless liquid at room temperature. In physiological literature, it has a lipid number of 18:2...

 and eicosapentaenoic acid

Eicosapentaenoic acid

Eicosapentaenoic acid is an omega-3 fatty acid. In physiological literature, it is given the name 20:5. It also has the trivial name timnodonic acid...

. Metabolism of arachidonic acid

Arachidonic acid

Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...

 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

COX-3

COX-3 is an enzyme that is encoded by the PTGS1 gene, but is not functional in humans. COX-3 is the third and most recently discovered cyclooxygenase isozyme, the others being COX-1 and COX-2...

 was identified in the CNS

Central nervous system

The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 of dogs, but does not result in a functional protein in humans.) This gene encodes COX-1, which regulates angiogenesis

Angiogenesis

Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...

 in endothelial cells. COX-1 is also involved in cell signaling

Cell signaling

Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...

 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. 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 nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin

Aspirin

Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

. 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 aspirin

Aspirin

Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

is effective at reducing cardiac events.

Further reading