"COX-1" redirects here. For mitochondrial cytochrome c oxidase subunit 1 (cox1), see MT-CO1.
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 PTGS1gene. In humans it is one of two cyclooxygenases.
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. This gene encodes COX-1, which regulates angiogenesis in endothelial cells. COX-1 is also involved in cell signaling and maintaining tissue homeostasis. 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.
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.
While metabolizing arachidonic acid primarily to PGG2, COX-1 also converts this fatty acid to small amounts of a racemic mixture of 15-Hydroxyicosatetraenoic acids (i.e., 15-HETEs) composed of ~22% 15(R)-HETE and ~78% 15(S)-HETE stereoisomers as well as a small amount of 11(R)-HETE. The two 15-HETE stereoisomers have intrinsic biological activities but, perhaps more importantly, can be further metabolized to a major class of anti-inflammatory agents, the lipoxins. In addition, PGG2 and PGH2 rearrange non-enzymatically to a mixture of 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 Malonyldialdehyde. and can be metabolized by CYP2S1 to 12-HHT (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. COX-1 is normally present in a variety of areas of the body, including not only the stomach but any site of inflammation.
^Yokoyama C, Tanabe T (December 1989). "Cloning of human gene encoding prostaglandin endoperoxide synthase and primary structure of the enzyme". Biochemical and Biophysical Research Communications. 165 (2): 888–94. doi:10.1016/S0006-291X(89)80049-X. PMID2512924.
^Serhan CN (2005). "Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 73 (3–4): 141–62. doi:10.1016/j.plefa.2005.05.002. PMID16005201.
^Wlodawer P, Samuelsson B (August 1973). "On the organization and mechanism of prostaglandin synthetase". The Journal of Biological Chemistry. 248 (16): 5673–8. PMID4723909.
^Frömel T, Kohlstedt K, Popp R, Yin X, Awwad K, Barbosa-Sicard E, Thomas AC, Lieberz R, Mayr M, Fleming I (January 2013). "Cytochrome P4502S1: a novel monocyte/macrophage fatty acid epoxygenase in human atherosclerotic plaques". Basic Research in Cardiology. 108 (1): 319. doi:10.1007/s00395-012-0319-8. PMID23224081.
^Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J, eds. (2008). Harrison's Principles of Internal Medicine (17th ed.). New York: McGraw-Hill Medical. p. 661. ISBN978-0-07-146633-2.
^Parker KL, Brunton LL, Lazo JS (2005). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill Medical Publishing Division. p. 1126. ISBN0-07-142280-3.
^Weitz JI (2008). "Chapter 112. Antiplatelet, Anticoagulant, and Fibrinolytic Drugs". In Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison's Principles of Internal Medicine (17th ed.). New York: McGraw-Hill Medical. ISBN978-0-07-146633-2.
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. doi:10.1016/S0960-0760(01)00187-X. PMID11897504.
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. doi:10.1016/j.semcdb.2006.09.001. PMID17071117.
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. PMID1587858.
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. doi:10.1016/0006-291X(92)91750-K. PMID1734857.
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. doi:10.1006/bbrc.1994.2152. PMID7521167.
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. doi:10.1074/jbc.270.42.24965. PMID7559624.
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. doi:10.1006/abbi.1995.1100. PMID7864630.
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. doi:10.1038/367243a0. PMID8121489.
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 / FEBS. 221 (3): 889–97. doi:10.1111/j.1432-1033.1994.tb18804.x. PMID8181472.
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. PMID8349699.
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. doi:10.1016/1055-8330(95)90021-7. PMID8581564.
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. PMID9435560.