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Pathway Description
Fish oil Prostaglandin G/H synthase 1 and 2 anti-inflammatory Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-07-26
Last Updated: 2023-11-27
Fish oil is made of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). It is an essential source of fatty acid (omega-3) indicated primarily as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia (FDA). Also, this molecule is indicated by the EMA as an adjuvant treatment in secondary prevention after myocardial infarction, in addition to other standard therapy (ie. statins, antiplatelet medicinal products, beta-blockers, ACE inhibitors). EPA and DHA do competition with arachidonic acids for both COX-1 and COX-2 enzymes. These are responsible for the conversion of arachidonic acid (an omega-6 fatty acid) into prostaglandins and thromboxanes, which are important mediators of inflammation and pain. Like DHA, EPA also interacts with the cyclooxygenase (COX) enzymes. EPA, as an omega-3 fatty acid, can competitively inhibit the activity of both COX-1 and COX-2 enzymes. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 convert arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase, or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. EPA and DHA inhibit the action of COX-1 and COX-2 on the endoplasmic reticulum membrane by doing competition with the normal substrate (arachidonic acid). This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. Fish oil is administered as an oral capsule or tablet, it can also be found as a parenteral emulsion when oral or enteral nutrition is not possible, insufficient, or contraindicated for different reasons.
References
Fish oil Prostaglandin G/H synthase 1 and 2 anti-inflammatory Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Weitz D, Weintraub H, Fisher E, Schwartzbard AZ: Fish oil for the treatment of cardiovascular disease. Cardiol Rev. 2010 Sep-Oct;18(5):258-63. doi: 10.1097/CRD.0b013e3181ea0de0.
Pubmed: 20699674
Visioli F, Giordano E, Nicod NM, Davalos A: Molecular targets of omega 3 and conjugated linoleic Fatty acids - "micromanaging" cellular response. Front Physiol. 2012 Feb 29;3:42. doi: 10.3389/fphys.2012.00042. eCollection 2012.
Pubmed: 22393325
Kremer JM: Fish Oil and Inflammation - A Fresh Look. J Rheumatol. 2017 Jun;44(6):713-716. doi: 10.3899/jrheum.161551.
Pubmed: 28572471
AlAmmar WA, Albeesh FH, Ibrahim LM, Algindan YY, Yamani LZ, Khattab RY: Effect of omega-3 fatty acids and fish oil supplementation on multiple sclerosis: a systematic review. Nutr Neurosci. 2021 Jul;24(7):569-579. doi: 10.1080/1028415X.2019.1659560. Epub 2019 Aug 28.
Pubmed: 31462182
Ellulu MS, Khaza'ai H, Abed Y, Rahmat A, Ismail P, Ranneh Y: Role of fish oil in human health and possible mechanism to reduce the inflammation. Inflammopharmacology. 2015 Jun;23(2-3):79-89. doi: 10.1007/s10787-015-0228-1. Epub 2015 Feb 14.
Pubmed: 25676565
Quin C, Vollman DM, Ghosh S, Haskey N, Estaki M, Pither J, Barnett JA, Jay MN, Birnie BW, Gibson DL: Fish oil supplementation reduces maternal defensive inflammation and predicts a gut bacteriome with reduced immune priming capacity in infants. ISME J. 2020 Aug;14(8):2090-2104. doi: 10.1038/s41396-020-0672-9. Epub 2020 May 12.
Pubmed: 32398661
Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B: A model for p53-induced apoptosis. Nature. 1997 Sep 18;389(6648):300-5. doi: 10.1038/38525.
Pubmed: 9305847
Jakobsson PJ, Thoren S, Morgenstern R, Samuelsson B: Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7220-5. doi: 10.1073/pnas.96.13.7220.
Pubmed: 10377395
Forsberg L, Leeb L, Thoren S, Morgenstern R, Jakobsson P: Human glutathione dependent prostaglandin E synthase: gene structure and regulation. FEBS Lett. 2000 Apr 7;471(1):78-82. doi: 10.1016/s0014-5793(00)01367-3.
Pubmed: 10760517
Miyata A, Hara S, Yokoyama C, Inoue H, Ullrich V, Tanabe T: Molecular cloning and expression of human prostacyclin synthase. Biochem Biophys Res Commun. 1994 May 16;200(3):1728-34. doi: 10.1006/bbrc.1994.1652.
Pubmed: 8185632
Chevalier D, Cauffiez C, Bernard C, Lo-Guidice JM, Allorge D, Fazio F, Ferrari N, Libersa C, Lhermitte M, D'Halluin JC, Broly F: Characterization of new mutations in the coding sequence and 5'-untranslated region of the human prostacylcin synthase gene (CYP8A1). Hum Genet. 2001 Feb;108(2):148-55. doi: 10.1007/s004390000444.
Pubmed: 11281454
Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. doi: 10.1038/414865a.
Pubmed: 11780052
Yokoyama C, Miyata A, Ihara H, Ullrich V, Tanabe T: Molecular cloning of human platelet thromboxane A synthase. Biochem Biophys Res Commun. 1991 Aug 15;178(3):1479-84. doi: 10.1016/0006-291x(91)91060-p.
Pubmed: 1714723
Ohashi K, Ruan KH, Kulmacz RJ, Wu KK, Wang LH: Primary structure of human thromboxane synthase determined from the cDNA sequence. J Biol Chem. 1992 Jan 15;267(2):789-93.
Pubmed: 1730669
Miyata A, Yokoyama C, Ihara H, Bandoh S, Takeda O, Takahashi E, Tanabe T: Characterization of the human gene (TBXAS1) encoding thromboxane synthase. Eur J Biochem. 1994 Sep 1;224(2):273-9. doi: 10.1111/j.1432-1033.1994.00273.x.
Pubmed: 7925341
Clark JD, Lin LL, Kriz RW, Ramesha CS, Sultzman LA, Lin AY, Milona N, Knopf JL: A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP. Cell. 1991 Jun 14;65(6):1043-51. doi: 10.1016/0092-8674(91)90556-e.
Pubmed: 1904318
Sharp JD, White DL, Chiou XG, Goodson T, Gamboa GC, McClure D, Burgett S, Hoskins J, Skatrud PL, Sportsman JR, et al.: Molecular cloning and expression of human Ca(2+)-sensitive cytosolic phospholipase A2. J Biol Chem. 1991 Aug 15;266(23):14850-3.
Pubmed: 1869522
Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. doi: 10.1038/nature04727.
Pubmed: 16710414
Yokoyama C, Tanabe T: Cloning of human gene encoding prostaglandin endoperoxide synthase and primary structure of the enzyme. Biochem Biophys Res Commun. 1989 Dec 15;165(2):888-94. doi: 10.1016/s0006-291x(89)80049-x.
Pubmed: 2512924
Funk CD, Funk LB, Kennedy ME, Pong AS, Fitzgerald GA: Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment. FASEB J. 1991 Jun;5(9):2304-12.
Pubmed: 1907252
Takahashi Y, Ueda N, Yoshimoto T, Yamamoto S, Yokoyama C, Miyata A, Tanabe T, Fuse I, Hattori A, Shibata A: Immunoaffinity purification and cDNA cloning of human platelet prostaglandin endoperoxide synthase (cyclooxygenase). Biochem Biophys Res Commun. 1992 Jan 31;182(2):433-8. doi: 10.1016/0006-291x(92)91750-k.
Pubmed: 1734857
Kosaka T, Miyata A, Ihara H, Hara S, Sugimoto T, Takeda O, Takahashi E, Tanabe T: Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2. Eur J Biochem. 1994 May 1;221(3):889-97. doi: 10.1111/j.1432-1033.1994.tb18804.x.
Pubmed: 8181472
Jones DA, Carlton DP, McIntyre TM, Zimmerman GA, Prescott SM: Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. J Biol Chem. 1993 Apr 25;268(12):9049-54.
Pubmed: 8473346
Hla T, Neilson K: Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7384-8. doi: 10.1073/pnas.89.16.7384.
Pubmed: 1380156
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