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.
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. 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. 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. COX-1 is normally present in a variety of areas of the body, including not only the stomach but any site of inflammation.
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. Research has shown that the inhibition of COX-1 is sufficient to explain why aspirin is effective at reducing cardiac events.
^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. PMID2512924.
Richards JA, Petrel TA, Brueggemeier RW (2002). "Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells". J. Steroid Biochem. Mol. Biol.80 (2): 203–12. doi:10.1016/S0960-0760(01)00187-X. PMID11897504.
Diaz A, Reginato AM, Jimenez SA (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". J. Biol. Chem.267 (15): 10816–22. PMID1587858.
Takahashi Y, Ueda N, Yoshimoto T, et al. (1992). "Immunoaffinity purification and cDNA cloning of human platelet prostaglandin endoperoxide synthase (cyclooxygenase)". Biochem. Biophys. Res. Commun.182 (2): 433–8. doi:10.1016/0006-291X(92)91750-K. PMID1734857.
Vane JR, Mitchell JA, Appleton I, et al. (1994). "Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation". Proc. Natl. Acad. Sci. U.S.A.91 (6): 2046–50. doi:10.1073/pnas.91.6.2046. PMC43306. PMID7510883.
Mollace V, Colasanti M, Rodino P, et al. (1994). "HIV coating gp 120 glycoprotein-dependent prostaglandin E2 release by human cultured astrocytoma cells is regulated by nitric oxide formation". Biochem. Biophys. Res. Commun.203 (1): 87–92. doi:10.1006/bbrc.1994.2152. PMID7521167.
Inoue H, Yokoyama C, Hara S, et al. (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". J. Biol. Chem.270 (42): 24965–71. doi:10.1074/jbc.270.42.24965. PMID7559624.
Ren Y, Loose-Mitchell DS, Kulmacz RJ (1995). "Prostaglandin H synthase-1: evaluation of C-terminus function". Arch. Biochem. Biophys.316 (2): 751–7. doi:10.1006/abbi.1995.1100. PMID7864630.
Picot D, Loll PJ, Garavito RM (1994). "The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1". Nature367 (6460): 243–9. doi:10.1038/367243a0. PMID8121489.
Otto JC, DeWitt DL, Smith WL (1993). "N-glycosylation of prostaglandin endoperoxide synthases-1 and -2 and their orientations in the endoplasmic reticulum". J. Biol. Chem.268 (24): 18234–42. PMID8349699.
Corasaniti MT, Melino G, Navarra M, et al. (1996). "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 : a journal for neurodegenerative disorders, neuroprotection, and neuroregeneration4 (3): 315–21. PMID8581564.
Ballif BA, Mincek NV, Barratt JT, et al. (1996). "Interaction of cyclooxygenases with an apoptosis- and autoimmunity-associated protein". Proc. Natl. Acad. Sci. U.S.A.93 (11): 5544–9. doi:10.1073/pnas.93.11.5544. PMC39283. PMID8643612.