Cyclooxygenase-1
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PTGS1
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| Location (UCSC) | Chr 9: 122.37 – 122.4 Mb | Chr 2: 36.12 – 36.14 Mb | |||||||
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Cyclooxygenase 1 (COX-1), also known as prostaglandin-endoperoxide synthase 1 (HUGO PTGS1), is an enzyme that in humans is encoded by the PTGS1 gene.[5][6] In humans it is one of two cyclooxygenases.
History
Cyclooxygenase (COX) is the central enzyme in the biosynthetic pathway to prostaglandins from
Gene and isozymes
There are two
COX-3 was identified in the central nervous system 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.[10]
Function
PGG2
, which is reduced to the corresponding alcohol, PGH2, by the enzyme's hydroperoxidase activity.
While metabolizing arachidonic acid primarily to PGG2, COX-1 also converts this fatty acid to small amounts of a racemic mixture of
Malonyldialdehyde.[13][14][15] and can be metabolized by CYP2S1 to 12-HHT[16][17] (see 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.[18][19] 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. Thromboxane A2, the major product of COX-1 in platelets, induces platelet aggregation.[20][21] The inhibition of COX-1 is sufficient to explain why low dose aspirin is effective at reducing cardiac events.
See also
- Arachidonic acid
- Cyclooxygenase
- Cyclooxygenase 2
- NSAID
- Discovery and development of COX-2 selective inhibitors
- COX-2 selective inhibitor
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000095303 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000047250 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 2512924.
- S2CID 46147389.
- PMID 12973429.
- S2CID 9407329.
- ^ "Entrez Gene: PTGS1 prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase)".
- PMID 12242329.
- PMID 19752399.
- PMID 16005201.
- PMID 4723909.
- PMID 4215079.
- PMID 9785378.
- PMID 21068195.
- S2CID 9158244.
- PMID 18549814.
- ISBN 978-0-07-146633-2.
- ISBN 0-07-142280-3.
- ISBN 978-0-07-146633-2.
Further reading
- Richards JA, Petrel TA, Brueggemeier RW (February 2002). "Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells". The Journal of Steroid Biochemistry and Molecular Biology. 80 (2): 203–12. S2CID 12728545.
- Wu T, Wu H, Wang J, Wang J (2011). "Expression and cellular localization of cyclooxygenases and prostaglandin E synthases in the hemorrhagic brain". Journal of Neuroinflammation. 8: 22. PMID 21385433.
- Jain S, Khuri FR, Shin DM (2004). "Prevention of head and neck cancer: current status and future prospects". Current Problems in Cancer. 28 (5): 265–86. PMID 15375804.
- Bingham S, Beswick PJ, Blum DE, Gray NM, Chessell IP (October 2006). "The role of the cylooxygenase pathway in nociception and pain". Seminars in Cell & Developmental Biology. 17 (5): 544–54. PMID 17071117.
- Diaz A, Reginato AM, Jimenez SA (May 1992). "Alternative splicing of human prostaglandin G/H synthase mRNA and evidence of differential regulation of the resulting transcripts by transforming growth factor beta 1, interleukin 1 beta, and tumor necrosis factor alpha". The Journal of Biological Chemistry. 267 (15): 10816–22. PMID 1587858.
- Takahashi Y, Ueda N, Yoshimoto T, Yamamoto S, Yokoyama C, Miyata A, Tanabe T, Fuse I, Hattori A, Shibata A (January 1992). "Immunoaffinity purification and cDNA cloning of human platelet prostaglandin endoperoxide synthase (cyclooxygenase)". Biochemical and Biophysical Research Communications. 182 (2): 433–8. PMID 1734857.
- Vane JR, Mitchell JA, Appleton I, Tomlinson A, Bishop-Bailey D, Croxtall J, Willoughby DA (March 1994). "Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation". Proceedings of the National Academy of Sciences of the United States of America. 91 (6): 2046–50. PMID 7510883.
- Mollace V, Colasanti M, Rodino P, Lauro GM, Nistico G (August 1994). "HIV coating gp 120 glycoprotein-dependent prostaglandin E2 release by human cultured astrocytoma cells is regulated by nitric oxide formation". Biochemical and Biophysical Research Communications. 203 (1): 87–92. PMID 7521167.
- Inoue H, Yokoyama C, Hara S, Tone Y, Tanabe T (October 1995). "Transcriptional regulation of human prostaglandin-endoperoxide synthase-2 gene by lipopolysaccharide and phorbol ester in vascular endothelial cells. Involvement of both nuclear factor for interleukin-6 expression site and cAMP response element". The Journal of Biological Chemistry. 270 (42): 24965–71. PMID 7559624.
- Ren Y, Loose-Mitchell DS, Kulmacz RJ (February 1995). "Prostaglandin H synthase-1: evaluation of C-terminus function". Archives of Biochemistry and Biophysics. 316 (2): 751–7. PMID 7864630.
- Picot D, Loll PJ, Garavito RM (January 1994). "The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1". Nature. 367 (6460): 243–9. S2CID 4340064.
- Kosaka T, Miyata A, Ihara H, Hara S, Sugimoto T, Takeda O, Takahashi E, Tanabe T (May 1994). "Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2". European Journal of Biochemistry. 221 (3): 889–97. PMID 8181472.
- Otto JC, DeWitt DL, Smith WL (August 1993). "N-glycosylation of prostaglandin endoperoxide synthases-1 and -2 and their orientations in the endoplasmic reticulum". The Journal of Biological Chemistry. 268 (24): 18234–42. PMID 8349699.
- O'Neill GP, Ford-Hutchinson AW (September 1993). "Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues". FEBS Letters. 330 (2): 156–60. S2CID 26397839.
- Corasaniti MT, Melino G, Navarra M, Garaci E, Finazzi-Agrò A, Nisticò G (September 1995). "Death of cultured human neuroblastoma cells induced by HIV-1 gp120 is prevented by NMDA receptor antagonists and inhibitors of nitric oxide and cyclooxygenase". Neurodegeneration. 4 (3): 315–21. PMID 8581564.
- Ballif BA, Mincek NV, Barratt JT, Wilson ML, Simmons DL (May 1996). "Interaction of cyclooxygenases with an apoptosis- and autoimmunity-associated protein". Proceedings of the National Academy of Sciences of the United States of America. 93 (11): 5544–9. PMID 8643612.
- Hla T (January 1996). "Molecular characterization of the 5.2 KB isoform of the human cyclooxygenase-1 transcript". Prostaglandins. 51 (1): 81–5. PMID 8900446.
- Mahida YR, Beltinger J, Makh S, Göke M, Gray T, Podolsky DK, Hawkey CJ (December 1997). "Adult human colonic subepithelial myofibroblasts express extracellular matrix proteins and cyclooxygenase-1 and -2". The American Journal of Physiology. 273 (6 Pt 1): G1341-8. PMID 9435560.
- Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN (May 1998). "Cyclooxygenase regulates angiogenesis induced by colon cancer cells". Cell. 93 (5): 705–16. S2CID 12704830.
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