PTGS1

Prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase)

PDB rendering based on 1diy.
Identifiers
Symbols PTGS1; COX1; COX3; PCOX1; PGG/HS; PGHS-1; PGHS1; PHS1; PTGHS
External IDs OMIM176805 MGI97797 HomoloGene743 GeneCards: PTGS1 Gene
EC number 1.14.99.1
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 5742 19224
Ensembl ENSG00000095303 ENSMUSG00000047250
UniProt P23219 Q3TJN9
RefSeq (mRNA) NM_000962.2 NM_008969.3
RefSeq (protein) NP_000953.2 NP_032995.1
Location (UCSC) Chr 9:
125.13 – 125.16 Mb
Chr 2:
36.09 – 36.11 Mb
PubMed search [1] [2]
"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]

Contents

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

  1. ^ Yokoyama C, Tanabe T (December 1989). "Cloning of human gene encoding prostaglandin endoperoxide synthase and primary structure of the enzyme". Biochem. Biophys. Res. Commun. 165 (2): 888–94. doi:10.1016/S0006-291X(89)80049-X. PMID 2512924. 
  2. ^ Funk CD, Funk LB, Kennedy ME, Pong AS, Fitzgerald GA (June 1991). "Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment". FASEB J. 5 (9): 2304–12. PMID 1907252. 
  3. ^ Bakhle YS (1999). "Structure of COX-1 and COX-2 enzymes and their interaction with inhibitors". Drugs Today 35 (4-5): 237–50. PMID 12973429. 
  4. ^ Sakamoto C (October 1998). "Roles of COX-1 and COX-2 in gastrointestinal pathophysiology". J. Gastroenterol. 33 (5): 618–24. doi:10.1007/s005350050147. PMID 9773924. 
  5. ^ "Entrez Gene: PTGS1 prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5742. 
  6. ^ Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, Simmons DL (October 2002). "COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression". Proc. Natl. Acad. Sci. U.S.A. 99 (21): 13926–31. doi:10.1073/pnas.162468699. PMC 129799. PMID 12242329. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=129799. 
  7. ^ a b MedicineNet.com[Internet]. New York:WebMD. [updated 2003 March 3; cited 2010 February 1] Available from: http://www.medterms.com/script/main/art.asp?articlekey=7123
  8. ^ Bruton LL, Lazo JS, Parker KL. Goodman & Gilman’s: the pharmacological basis of therapeutics. 11th edition. New York: McGraw-Hill; 2006. p. 661.
  9. ^ AWS-Law.com [Internet]. Florida. [cited 2010 February 1] Available from: http://www.aws-law.com/about.asp.
  10. ^ Bruton LL, Lazo JS, Parker KL. Goodman & Gilman’s: the pharmacological basis of therapeutics. 11th edition. New York: McGraw-Hill; 2006. p. 1126.
  11. ^ Weitz Jeffrey I, "Chapter 112. Antiplatelet, Anticoagulant, and Fibrinolytic Drugs" (Chapter). Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles of Internal Medicine, 17e: http://www.accessmedicine.com/content.aspx?aID=2891975.

Further reading