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Pathway Description
Etodolac Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2013-08-04
Last Updated: 2022-10-17
Etodolac is a non-steroidal anti-inflammatory drug (NSAID) that can be used to treat rheumatoid arthritis and osteoarthritis. Most NSAIDs are non-selective prostaglandin G/H synthase (a.k.a. cyclooxygenase or COX) inhibitors that act on both prostaglandin G/H synthase 1 and 2 (COX-1 and -2). Prostaglandin G/H synthase catalyzes the conversion of arachidonic acid to a number of prostaglandins involved in fever, pain, swelling, inflammation, and platelet aggregation. NSAIDs antagonize COX by binding to the upper portion of the active site, preventing its substrate, arachidonic acid, from entering the active site. The analgesic, antipyretic and anti-inflammatory effects of NSAIDs occur as a result of decreased prostaglandin synthesis. Etodolac was previously thought to be a non-selective COX inhibitor; however, it is now know that it is five to fifty times more selective for COX-2 than COX-1. The first part of this figure depicts the anti-inflammatory, analgesic and antipyretic pathway of etodolac. The latter portion of this figure depicts etodolac’s potential involvement in platelet aggregation. Prostaglandin synthesis varies across different tissue types. Platelets, anuclear cells derived from fragmentation from megakaryocytes, contain COX-1, but not COX-2. COX-1 activity in platelets is required for thromboxane A2 (TxA2)-mediated platelet aggregation. Platelet activation and coagulation do not normally occur in intact blood vessels. After blood vessel injury, platelets adhere to the subendothelial collagen at the site of injury. Activation of collagen receptors initiates phospholipase C (PLC)-mediated signaling cascades resulting in the release of intracellular calcium from the dense tubula system. The increase in intracellular calcium activates kinases required for morphological change, transition to procoagulant surface, secretion of granular contents, activation of glycoproteins, and the activation of phospholipase A2 (PLA2). Activation of PLA2 results in the liberation of arachidonic acid, a precursor to prostaglandin synthesis, from membrane phospholipids. The accumulation of TxA2, ADP and thrombin mediates further platelet recruitment and signal amplification. TxA2 and ADP stimulate their respective G-protein coupled receptors, thomboxane A2 receptor and P2Y purinoreceptor 12, and inhibit the production of cAMP via adenylate cyclase inhibition. This counteracts the adenylate cyclase stimulatory effects of the platelet aggregation inhibitor, PGI2, produced by neighbouring endothelial cells. Platelet adhesion, cytoskeletal remodeling, granular secretion and signal amplification are independent processes that lead to the activation of the fibrinogen receptor. Fibrinogen receptor activation exposes fibrinogen binding sites and allows platelet cross-linking and aggregation to occur. Neighbouring endothelial cells found in blood vessels express both COX-1 and COX-2. COX-2 in endothelial cells mediates the synthesis of PGI2, an effective platelet aggregation inhibitor and vasodilator, while COX-1 mediates vasoconstriction and stimulates platelet aggregation. PGI2 produced by endothelial cells encounters platelets in the blood stream and binds to the G-protein coupled prostacyclin receptor. This causes G-protein mediated activation of adenylate cyclase, which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic AMP (cAMP). Four cAMP molecules then bind to the regulatory subunits of the inactive cAMP-dependent protein kinase holoenzyme causing dissociation of the regulatory subunits and leaving two active catalytic subunit monomers. The active subunits of cAMP-dependent protein kinase catalyze the phosphorylation of a number of proteins. Phosphorylation of inositol 1,4,5-trisphosphate receptor type 1 on the endoplasmic reticulum (ER) inhibits the release of calcium from the ER. This in turn inhibits the calcium-dependent events, including PLA2 activation, involved in platelet activation and aggregation. Inhibition of PLA2 decreases intracellular TxA2 and inhibits the platelet aggregation pathway. cAMP-dependent kinase also phosphorylates the actin-associated protein, vasodilator-stimulated phosphoprotein. Phosphorylation inhibits protein activity, which includes cytoskeleton reorganization and platelet activation. Etodolac preferentially inhibits COX-2 with little activity against COX-1. COX-2 inhibition in endothelial cells decreases the production of PGI2 and the ability of these cells to inhibit platelet aggregation and stimulate vasodilation. These effects are thought to be responsible for the adverse cardiovascular effects observed with other selective COX-2 inhibitors, such as rofecoxib, which has since been withdrawn from the market.
References
Etodolac Pathway References
Apo-Etodolac. (2009). e-CPS (online version of Compendium of Pharmaceuticals and Specialties). Retrieved August 15, 2009.
Botting, R., & Botting, J. Cyclooxygenases. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology. (2004) p.279-283. Berlin, Germany: Springer.
Breyer, R.M., & Breyer, M.D. Prostanoids. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology. (2004) p. 752-757. Berlin, Germany: Springer.
Offermanns, S. Antiplatelet drugs. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology. (2004) p.106-109. Berlin, Germany: Springer.
Andelman SY: Etodolac, aspirin, and placebo in patients with degenerative joint disease: a twelve-week study. Clin Ther. 1983;5(6):651-61.
Pubmed: 6226358
Edwards W: Etodolac, aspirin, and placebo in patients with rheumatoid arthritis: a 12-week study. Clin Ther. 1983;5(5):495-503.
Pubmed: 6225520
Balfour JA, Buckley MM: Etodolac. A reappraisal of its pharmacology and therapeutic use in rheumatic diseases and pain states. Drugs. 1991 Aug;42(2):274-99. doi: 10.2165/00003495-199142020-00008.
Pubmed: 1717225
Bellamy N: Etodolac in the management of pain: a clinical review of a multipurpose analgesic. Inflammopharmacology. 1997;5(2):139-52. doi: 10.1007/s10787-997-0023-8.
Pubmed: 17694363
Bacon PA: An overview of the efficacy of etodolac in arthritic disorders. Eur J Rheumatol Inflamm. 1990;10(1):22-34.
Pubmed: 2146130
Inoue K, Motonaga A, Nishimura T, Yokota M, Miki N, Fujisawa H, Ueda F, Shibata Y, Kimura K: Mechanism of anti-inflammatory action of etodolac. Arzneimittelforschung. 1991 Mar;41(3):235-9.
Pubmed: 1714278
Rao CV, Reddy BS: NSAIDs and chemoprevention. Curr Cancer Drug Targets. 2004 Feb;4(1):29-42.
Pubmed: 14965265
Takayama T, Nagashima H, Maeda M, Nojiri S, Hirayama M, Nakano Y, Takahashi Y, Sato Y, Sekikawa H, Mori M, Sonoda T, Kimura T, Kato J, Niitsu Y: Randomized double-blind trial of sulindac and etodolac to eradicate aberrant crypt foci and to prevent sporadic colorectal polyps. Clin Cancer Res. 2011 Jun 1;17(11):3803-11. doi: 10.1158/1078-0432.CCR-10-2395. Epub 2011 Mar 8.
Pubmed: 21385928
Wang S, Dai Y, Kogure Y, Yamamoto S, Zhang W, Noguchi K: Etodolac activates and desensitizes transient receptor potential ankyrin 1. J Neurosci Res. 2013 Dec;91(12):1591-8. doi: 10.1002/jnr.23274. Epub 2013 Aug 30.
Pubmed: 24027177
Ishiguro N, Hanaoka A, Okada T, Ito M: Efficacy and safety of celecoxib compared with placebo and etodolac for acute postoperative pain: a multicenter, double-blind, randomized, parallel-group, controlled trial. Nagoya J Med Sci. 2015 Feb;77(1-2):81-93.
Pubmed: 25797973
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
Kikuta Y, Miyauchi Y, Kusunose E, Kusunose M: Expression and molecular cloning of human liver leukotriene B4 omega-hydroxylase (CYP4F2) gene. DNA Cell Biol. 1999 Sep;18(9):723-30. doi: 10.1089/104454999315006.
Pubmed: 10492403
Zhang X, Chen L, Hardwick JP: Promoter activity and regulation of the CYP4F2 leukotriene B(4) omega-hydroxylase gene by peroxisomal proliferators and retinoic acid in HepG2 cells. Arch Biochem Biophys. 2000 Jun 15;378(2):364-76. doi: 10.1006/abbi.2000.1836.
Pubmed: 10860554
Kikuta Y, Kusunose E, Kusunose M: Characterization of human liver leukotriene B(4) omega-hydroxylase P450 (CYP4F2). J Biochem. 2000 Jun;127(6):1047-52. doi: 10.1093/oxfordjournals.jbchem.a022696.
Pubmed: 10833273
Minami M, Ohno S, Kawasaki H, Radmark O, Samuelsson B, Jornvall H, Shimizu T, Seyama Y, Suzuki K: Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase. Complete primary structure of an enzyme involved in eicosanoid synthesis. J Biol Chem. 1987 Oct 15;262(29):13873-6.
Pubmed: 3654641
Funk CD, Radmark O, Fu JY, Matsumoto T, Jornvall H, Shimizu T, Samuelsson B: Molecular cloning and amino acid sequence of leukotriene A4 hydrolase. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6677-81. doi: 10.1073/pnas.84.19.6677.
Pubmed: 2821541
Mancini JA, Evans JF: Cloning and characterization of the human leukotriene A4 hydrolase gene. Eur J Biochem. 1995 Jul 1;231(1):65-71. doi: 10.1111/j.1432-1033.1995.tb20671.x.
Pubmed: 7628486
Lam BK, Penrose JF, Freeman GJ, Austen KF: Expression cloning of a cDNA for human leukotriene C4 synthase, an integral membrane protein conjugating reduced glutathione to leukotriene A4. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7663-7. doi: 10.1073/pnas.91.16.7663.
Pubmed: 8052639
Welsch DJ, Creely DP, Hauser SD, Mathis KJ, Krivi GG, Isakson PC: Molecular cloning and expression of human leukotriene-C4 synthase. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9745-9. doi: 10.1073/pnas.91.21.9745.
Pubmed: 7937884
Penrose JF, Spector J, Baldasaro M, Xu K, Boyce J, Arm JP, Austen KF, Lam BK: Molecular cloning of the gene for human leukotriene C4 synthase. Organization, nucleotide sequence, and chromosomal localization to 5q35. J Biol Chem. 1996 May 10;271(19):11356-61. doi: 10.1074/jbc.271.19.11356.
Pubmed: 8626689
Rajpert-De Meyts E, Heisterkamp N, Groffen J: Cloning and nucleotide sequence of human gamma-glutamyl transpeptidase. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8840-4. doi: 10.1073/pnas.85.23.8840.
Pubmed: 2904146
Sakamuro D, Yamazoe M, Matsuda Y, Kangawa K, Taniguchi N, Matsuo H, Yoshikawa H, Ogasawara N: The primary structure of human gamma-glutamyl transpeptidase. Gene. 1988 Dec 15;73(1):1-9. doi: 10.1016/0378-1119(88)90307-1.
Pubmed: 2907498
Pitot HC, Goodspeed D, Dunn T, Hendrich S, Maronpot RR, Moran S: Regulation of the expression of some genes for enzymes of glutathione metabolism in hepatotoxicity and hepatocarcinogenesis. Toxicol Appl Pharmacol. 1989 Jan;97(1):23-34. doi: 10.1016/0041-008x(89)90052-5.
Pubmed: 2563599
Forsberg L, de Faire U, Morgenstern R: Low yield of polymorphisms from EST blast searching: analysis of genes related to oxidative stress and verification of the P197L polymorphism in GPX1. Hum Mutat. 1999;13(4):294-300. doi: 10.1002/(SICI)1098-1004(1999)13:4<294::AID-HUMU6>3.0.CO;2-5.
Pubmed: 10220143
Kote-Jarai Z, Durocher F, Edwards SM, Hamoudi R, Jackson RA, Ardern-Jones A, Murkin A, Dearnaley DP, Kirby R, Houlston R, Easton DF, Eeles R: Association between the GCG polymorphism of the selenium dependent GPX1 gene and the risk of young onset prostate cancer. Prostate Cancer Prostatic Dis. 2002;5(3):189-92. doi: 10.1038/sj.pcan.4500569.
Pubmed: 12496980
Sukenaga Y, Ishida K, Takeda T, Takagi K: cDNA sequence coding for human glutathione peroxidase. Nucleic Acids Res. 1987 Sep 11;15(17):7178. doi: 10.1093/nar/15.17.7178.
Pubmed: 3658677
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
Nagata A, Suzuki Y, Igarashi M, Eguchi N, Toh H, Urade Y, Hayaishi O: Human brain prostaglandin D synthase has been evolutionarily differentiated from lipophilic-ligand carrier proteins. Proc Natl Acad Sci U S A. 1991 May 1;88(9):4020-4. doi: 10.1073/pnas.88.9.4020.
Pubmed: 1902577
White DM, Mikol DD, Espinosa R, Weimer B, Le Beau MM, Stefansson K: Structure and chromosomal localization of the human gene for a brain form of prostaglandin D2 synthase. J Biol Chem. 1992 Nov 15;267(32):23202-8.
Pubmed: 1385416
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Penning TM, Burczynski ME, Jez JM, Lin HK, Ma H, Moore M, Ratnam K, Palackal N: Structure-function aspects and inhibitor design of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3). Mol Cell Endocrinol. 2001 Jan 22;171(1-2):137-49. doi: 10.1016/s0303-7207(00)00426-3.
Pubmed: 11165022
Lovering AL, Ride JP, Bunce CM, Desmond JC, Cummings SM, White SA: Crystal structures of prostaglandin D(2) 11-ketoreductase (AKR1C3) in complex with the nonsteroidal anti-inflammatory drugs flufenamic acid and indomethacin. Cancer Res. 2004 Mar 1;64(5):1802-10.
Pubmed: 14996743
Qin KN, New MI, Cheng KC: Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Biol. 1993 Dec;46(6):673-9.
Pubmed: 8274401
Arachidonic Acid Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (4th ed.) (2002) Amsterdam; Boston: Elsevier.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Kroetz DL, Zeldin DC: Cytochrome P450 pathways of arachidonic acid metabolism. Curr Opin Lipidol. 2002 Jun;13(3):273-83.
Pubmed: 12045397
Zeldin DC: Epoxygenase pathways of arachidonic acid metabolism. J Biol Chem. 2001 Sep 28;276(39):36059-62. doi: 10.1074/jbc.R100030200. Epub 2001 Jul 12.
Pubmed: 11451964
Ondrey FG: Arachidonic acid metabolism: a primer for head and neck surgeons. Head Neck. 1998 Jul;20(4):334-49.
Pubmed: 9588707
Sigal E: The molecular biology of mammalian arachidonic acid metabolism. Am J Physiol. 1991 Feb;260(2 Pt 1):L13-28. doi: 10.1152/ajplung.1991.260.2.L13.
Pubmed: 1899973
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
Kikuta Y, Miyauchi Y, Kusunose E, Kusunose M: Expression and molecular cloning of human liver leukotriene B4 omega-hydroxylase (CYP4F2) gene. DNA Cell Biol. 1999 Sep;18(9):723-30. doi: 10.1089/104454999315006.
Pubmed: 10492403
Zhang X, Chen L, Hardwick JP: Promoter activity and regulation of the CYP4F2 leukotriene B(4) omega-hydroxylase gene by peroxisomal proliferators and retinoic acid in HepG2 cells. Arch Biochem Biophys. 2000 Jun 15;378(2):364-76. doi: 10.1006/abbi.2000.1836.
Pubmed: 10860554
Kikuta Y, Kusunose E, Kusunose M: Characterization of human liver leukotriene B(4) omega-hydroxylase P450 (CYP4F2). J Biochem. 2000 Jun;127(6):1047-52. doi: 10.1093/oxfordjournals.jbchem.a022696.
Pubmed: 10833273
Minami M, Ohno S, Kawasaki H, Radmark O, Samuelsson B, Jornvall H, Shimizu T, Seyama Y, Suzuki K: Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase. Complete primary structure of an enzyme involved in eicosanoid synthesis. J Biol Chem. 1987 Oct 15;262(29):13873-6.
Pubmed: 3654641
Funk CD, Radmark O, Fu JY, Matsumoto T, Jornvall H, Shimizu T, Samuelsson B: Molecular cloning and amino acid sequence of leukotriene A4 hydrolase. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6677-81. doi: 10.1073/pnas.84.19.6677.
Pubmed: 2821541
Mancini JA, Evans JF: Cloning and characterization of the human leukotriene A4 hydrolase gene. Eur J Biochem. 1995 Jul 1;231(1):65-71. doi: 10.1111/j.1432-1033.1995.tb20671.x.
Pubmed: 7628486
Lam BK, Penrose JF, Freeman GJ, Austen KF: Expression cloning of a cDNA for human leukotriene C4 synthase, an integral membrane protein conjugating reduced glutathione to leukotriene A4. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7663-7. doi: 10.1073/pnas.91.16.7663.
Pubmed: 8052639
Welsch DJ, Creely DP, Hauser SD, Mathis KJ, Krivi GG, Isakson PC: Molecular cloning and expression of human leukotriene-C4 synthase. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9745-9. doi: 10.1073/pnas.91.21.9745.
Pubmed: 7937884
Penrose JF, Spector J, Baldasaro M, Xu K, Boyce J, Arm JP, Austen KF, Lam BK: Molecular cloning of the gene for human leukotriene C4 synthase. Organization, nucleotide sequence, and chromosomal localization to 5q35. J Biol Chem. 1996 May 10;271(19):11356-61. doi: 10.1074/jbc.271.19.11356.
Pubmed: 8626689
Rajpert-De Meyts E, Heisterkamp N, Groffen J: Cloning and nucleotide sequence of human gamma-glutamyl transpeptidase. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8840-4. doi: 10.1073/pnas.85.23.8840.
Pubmed: 2904146
Sakamuro D, Yamazoe M, Matsuda Y, Kangawa K, Taniguchi N, Matsuo H, Yoshikawa H, Ogasawara N: The primary structure of human gamma-glutamyl transpeptidase. Gene. 1988 Dec 15;73(1):1-9. doi: 10.1016/0378-1119(88)90307-1.
Pubmed: 2907498
Pitot HC, Goodspeed D, Dunn T, Hendrich S, Maronpot RR, Moran S: Regulation of the expression of some genes for enzymes of glutathione metabolism in hepatotoxicity and hepatocarcinogenesis. Toxicol Appl Pharmacol. 1989 Jan;97(1):23-34. doi: 10.1016/0041-008x(89)90052-5.
Pubmed: 2563599
Forsberg L, de Faire U, Morgenstern R: Low yield of polymorphisms from EST blast searching: analysis of genes related to oxidative stress and verification of the P197L polymorphism in GPX1. Hum Mutat. 1999;13(4):294-300. doi: 10.1002/(SICI)1098-1004(1999)13:4<294::AID-HUMU6>3.0.CO;2-5.
Pubmed: 10220143
Kote-Jarai Z, Durocher F, Edwards SM, Hamoudi R, Jackson RA, Ardern-Jones A, Murkin A, Dearnaley DP, Kirby R, Houlston R, Easton DF, Eeles R: Association between the GCG polymorphism of the selenium dependent GPX1 gene and the risk of young onset prostate cancer. Prostate Cancer Prostatic Dis. 2002;5(3):189-92. doi: 10.1038/sj.pcan.4500569.
Pubmed: 12496980
Sukenaga Y, Ishida K, Takeda T, Takagi K: cDNA sequence coding for human glutathione peroxidase. Nucleic Acids Res. 1987 Sep 11;15(17):7178. doi: 10.1093/nar/15.17.7178.
Pubmed: 3658677
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
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