2.0 2012-05-31 10:25:22 -0600 2015-09-13 12:56:07 -0600 ECMDB00273 M2MDB000114 Thymidine Thymidine is non-toxic and is a naturally occurring compound that exists in all living organisms and DNA viruses. 25% of DNA is composed of thymidine. RNA does not have thymidine and has uridine instead. Thymidine is a chemical compound which is a pyrimidine nucleoside. Thymidine is the DNA base T, which pairs with adenosine in double stranded DNA. 1-(2-Deoxy-b-D-erythro-pentofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione 1-(2-Deoxy-b-delta-erythro-pentofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione 1-(2-Deoxy-b-δ-erythro-pentofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione 1-(2-Deoxy-beta-delta-erythro-pentofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione 1-(2-Deoxy-β-δ-erythro-pentofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione 1-[4-Hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-pyrimidine-2,4-dione 2'-Deoxy-5-methyl-Uridine 2'-Deoxythymidine 5-Methyl-2'-deoxyuridine 5-Methyldeoxyuridine Deoxyribothymidine Deoxythymidine DT DThyd Thymidin Thymidine Thymine 2-desoxyriboside Thymine deoxyriboside Thymine-1 2-deoxy-b-D-Ribofuranoside Thymine-1 2-deoxy-b-delta-ribofuranoside Thymine-1 2-deoxy-b-δ-ribofuranoside Thymine-1 2-deoxy-beta-delta-Ribofuranoside Thymine-1 2-deoxy-β-δ-ribofuranoside C10H14N2O5 242.2286 242.090271568 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione thymidine 50-89-5 CC1=CN([C@H]2C[C@H](O)[C@@H](CO)O2)C(=O)NC1=O InChI=1S/C10H14N2O5/c1-5-3-12(10(16)11-9(5)15)8-2-6(14)7(4-13)17-8/h3,6-8,13-14H,2,4H2,1H3,(H,11,15,16)/t6-,7+,8+/m0/s1 IQFYYKKMVGJFEH-XLPZGREQSA-N Solid Cytosol Extra-organism Periplasm logp -1.32 ALOGPS logs -0.56 ALOGPS solubility 6.68e+01 g/l ALOGPS logp -1.1 ChemAxon pka_strongest_acidic 9.96 ChemAxon pka_strongest_basic -3 ChemAxon iupac 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione ChemAxon average_mass 242.2286 ChemAxon mono_mass 242.090271568 ChemAxon smiles CC1=CN([C@H]2C[C@H](O)[C@@H](CO)O2)C(=O)NC1=O ChemAxon formula C10H14N2O5 ChemAxon inchi InChI=1S/C10H14N2O5/c1-5-3-12(10(16)11-9(5)15)8-2-6(14)7(4-13)17-8/h3,6-8,13-14H,2,4H2,1H3,(H,11,15,16)/t6-,7+,8+/m0/s1 ChemAxon inchikey IQFYYKKMVGJFEH-XLPZGREQSA-N ChemAxon polar_surface_area 99.1 ChemAxon refractivity 55.41 ChemAxon polarizability 23.06 ChemAxon rotatable_bond_count 2 ChemAxon acceptor_count 5 ChemAxon donor_count 3 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Pyrimidine metabolism The metabolism of pyrimidines begins with L-glutamine interacting with water molecule and a hydrogen carbonate through an ATP driven carbamoyl phosphate synthetase resulting in a hydrogen ion, an ADP, a phosphate, an L-glutamic acid and a carbamoyl phosphate. The latter compound interacts with an L-aspartic acid through a aspartate transcarbamylase resulting in a phosphate, a hydrogen ion and a N-carbamoyl-L-aspartate. The latter compound interacts with a hydrogen ion through a dihydroorotase resulting in the release of a water molecule and a 4,5-dihydroorotic acid. This compound interacts with an ubiquinone-1 through a dihydroorotate dehydrogenase, type 2 resulting in a release of an ubiquinol-1 and an orotic acid. The orotic acid then interacts with a phosphoribosyl pyrophosphate through a orotate phosphoribosyltransferase resulting in a pyrophosphate and an orotidylic acid. The latter compound then interacts with a hydrogen ion through an orotidine-5 '-phosphate decarboxylase, resulting in an release of carbon dioxide and an Uridine 5' monophosphate. The Uridine 5' monophosphate process to get phosphorylated by an ATP driven UMP kinase resulting in the release of an ADP and an Uridine 5--diphosphate. Uridine 5-diphosphate can be metabolized in multiple ways in order to produce a Deoxyuridine triphosphate. 1.-Uridine 5-diphosphate interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in the release of a water molecule and an oxidized thioredoxin and an dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate. 2.-Uridine 5-diphosphate interacts with a reduced NrdH glutaredoxin-like protein through a Ribonucleoside-diphosphate reductase 1 resulting in a release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate. 3.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate. The latter compound interacts with a reduced flavodoxin through ribonucleoside-triphosphate reductase resulting in the release of an oxidized flavodoxin, a water molecule and a Deoxyuridine triphosphate 4.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate interacts with a reduced flavodoxin through a ribonucleoside-triphosphate reductase resulting in the release of a water molecule, an oxidized flavodoxin and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. 5.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP then interacts with a reduced NrdH glutaredoxin-like protein through a ribonucleoside-diphosphate reductase 2 resulting in the release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. 6.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in a release of a water molecule, an oxidized thioredoxin and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. The deoxyuridine triphosphate then interacts with a water molecule through a nucleoside triphosphate pyrophosphohydrolase resulting in a release of a hydrogen ion, a phosphate and a dUMP. The dUMP then interacts with a methenyltetrahydrofolate through a thymidylate synthase resulting in a dihydrofolic acid and a 5-thymidylic acid. Then 5-thymidylic acid is then phosphorylated through a nucleoside diphosphate kinase resulting in the release of an ADP and thymidine 5'-triphosphate. PW000942 ec00240 Metabolic Drug metabolism - other enzymes ec00983 Metabolic pathways eco01100 pyrimidine deoxyribonucleosides degradation The degradation of deoxycytidine starts with deoxycytidine being introduced into the cytosol through either a nupG or nupC symporter. Once inside, it can can be degrade through water,a hydrogen ion and a deoxycytidien deaminsa resultin in the release of a ammonium and a a deoxyuridine. The deoxyuridine is then degraded through a uracil phosphorylase resulting in the release of a deoxyribose 1-phosphate and a uracil. The degradation of thymidine starts with thymidine being introduced into the cytosol through either a nupG or nupC symporter. Thymidine is then degrades through a phosphorylase resulting in the release of a thymine and a deoxyribose 1-phosphate. PW002063 Metabolic salvage pathways of pyrimidine deoxyribonucleotides The pathway begins with the introduction of deoxycytidine into the cytosol, either through a nupG symporter or a nupC symporter. Once inside it is deaminated when reacting with a water molecule, a hydrogen ion and a deoxycytidine deaminase resulting in the release of an ammonium and a deoxyuridine. Deoxyuridine can also be imported through a nupG symporter or a nupC symporter. Deoxyuridine can react with an ATP through a deoxyuridine kinase resulting in the release of a ADP , a hydrogen ion and a dUMP. Deoxyuridine can also react with a phosphate through a uracil phosphorylase resulting in the release of a uracil and a deoxy-alpha-D-ribose 1-phosphate. This compound in turn reacts with a thymine through a thymidine phosphorylase resulting in the release of a phosphate and a thymidine. Thymidine in turn reacts with an ATP through a thymidine kinase resulting in a release of an ADP, a hydrogen ion and a dTMP PW002061 Metabolic salvage pathways of pyrimidine deoxyribonucleotides PWY0-181 pyrimidine deoxyribonucleosides degradation PWY0-1298 Specdb::CMs 1960 Specdb::CMs 1993 Specdb::CMs 2811 Specdb::CMs 31112 Specdb::CMs 31113 Specdb::CMs 32286 Specdb::CMs 32329 Specdb::CMs 32330 Specdb::CMs 37397 Specdb::CMs 157927 Specdb::CMs 1056510 Specdb::CMs 1056512 Specdb::CMs 1056514 Specdb::CMs 1056516 Specdb::CMs 1056518 Specdb::CMs 1056519 Specdb::CMs 1056521 Specdb::CMs 1056523 Specdb::CMs 1056525 Specdb::CMs 1056527 Specdb::CMs 1056529 Specdb::EiMs 1979 Specdb::NmrOneD 1309 Specdb::NmrOneD 4904 Specdb::NmrOneD 4905 Specdb::NmrOneD 6382 Specdb::NmrOneD 6383 Specdb::NmrOneD 6384 Specdb::NmrOneD 6385 Specdb::NmrOneD 6386 Specdb::NmrOneD 6387 Specdb::NmrOneD 6388 Specdb::NmrOneD 6389 Specdb::NmrOneD 6390 Specdb::NmrOneD 6391 Specdb::NmrOneD 6392 Specdb::NmrOneD 6393 Specdb::NmrOneD 6394 Specdb::NmrOneD 6395 Specdb::NmrOneD 6396 Specdb::NmrOneD 6397 Specdb::NmrOneD 6398 Specdb::NmrOneD 6399 Specdb::NmrOneD 6400 Specdb::NmrOneD 6401 Specdb::MsMs 478 Specdb::MsMs 479 Specdb::MsMs 480 Specdb::MsMs 3904 Specdb::MsMs 3905 Specdb::MsMs 3906 Specdb::MsMs 3907 Specdb::MsMs 3908 Specdb::MsMs 3909 Specdb::MsMs 3910 Specdb::MsMs 3911 Specdb::MsMs 3912 Specdb::MsMs 3913 Specdb::MsMs 3914 Specdb::MsMs 3915 Specdb::MsMs 3916 Specdb::MsMs 3917 Specdb::MsMs 178890 Specdb::MsMs 178891 Specdb::MsMs 178892 Specdb::MsMs 181215 Specdb::MsMs 181216 Specdb::MsMs 181217 Specdb::MsMs 438495 Specdb::MsMs 438496 Specdb::NmrTwoD 1012 Specdb::NmrTwoD 1252 HMDB00273 5789 5585 C00214 17748 THYMIDINE THM Thymidine Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. 21097882 Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. 22080510 van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. 17765195 Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. 18331064 Eells JT, Spector R: Purine and pyrimidine base and nucleoside concentrations in human cerebrospinal fluid and plasma. Neurochem Res. 1983 Nov;8(11):1451-7. 6656991 Zhao R, Zhang S, Hanscom M, Chattopadhyay S, Goldman ID: Loss of reduced folate carrier function and folate depletion result in enhanced pemetrexed inhibition of purine synthesis. Clin Cancer Res. 2005 Feb 1;11(3):1294-301. 15709201 Robins HI, Tutsch K, Katschinski DM, Jacobson E, Mehta M, Olsen M, Cohen JD, Tiggelaar CL, Arzoomanian RZ, Alberti D, Feierabend C, Wilding G: Phase I trial of intravenous thymidine and carboplatin in patients with advanced cancer. J Clin Oncol. 1999 Sep;17(9):2922-31. 10561372 Vogel W, Schempp W, Sigwarth I: Comparison of thymidine, fluorodeoxyuridine, hydroxyurea, and methotrexate blocking at the G1/S phase transition of the cell cycle, studied by replication patterns. Hum Genet. 1978 Dec 18;45(2):193-8. 153886 Schill WB, Miska W: Possible effects of the kallikrein-kinin system on male reproductive functions. Andrologia. 1992 Mar-Apr;24(2):69-75. 1318646 Grinlinton FM, Skinner MA, Birchall NM, Tan PL: Gamma delta + T cells from patients with psoriatic and rheumatoid arthritis respond to streptococcal antigen. J Rheumatol. 1993 Jun;20(6):982-7. 8350335 Schulz CA, Mehta MP, Badie B, McGinn CJ, Robins HI, Hayes L, Chappell R, Volkman J, Binger K, Arzoomanian R, Simon K, Alberti D, Feierabend C, Tutsch KD, Kunugi KA, Wilding G, Kinsella TJ: Continuous 28-day iododeoxyuridine infusion and hyperfractionated accelerated radiotherapy for malignant glioma: a phase I clinical study. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):1107-15. 15234045 Isoda K, Kim H, Hamamoto Y: A study on the mesothelial cell kinetics in pleural effusions by DNA cytophotometry and autoradiography with tritiated thymidine. Acta Pathol Jpn. 1984 Jul;34(4):775-83. 6485796 Ashkenazi S, Cleary KR, Pickering LK, Murray BE, Cleary TG: The association of Shiga toxin and other cytotoxins with the neurologic manifestations of shigellosis. J Infect Dis. 1990 May;161(5):961-5. 2324546 Abelson HT, Fosburg MT, Beardsley GP, Goorin AM, Gorka C, Link M, Link D: Methotrexate-induced renal impairment: clinical studies and rescue from systemic toxicity with high-dose leucovorin and thymidine. J Clin Oncol. 1983 Mar;1(3):208-16. 6607976 Svendsen LB, Stener Jorgensen F, Hart Hansen O, Johansen A, Horn T, Larsen JK: Influence of the prostaglandin E1 analogue Rioprostil on the human gastric mucosa. Digestion. 1987;37(1):29-34. 3111919 Herdewijn, P.; Kerremans, L.; Wigerinck, P.; Vandendriessche, F.; Van Aerschot, A. Synthesis of thymidine from 5-iodo-2'-deoxyuridine. Tetrahedron Letters (1991), 32(34), 4397-400. http://hmdb.ca/system/metabolites/msds/000/000/201/original/HMDB00273.pdf?1358896048 Protein ushA P07024 USHA_ECOLI ushA http://ecmdb.ca/proteins/P07024.xml Thymidine phosphorylase P07650 TYPH_ECOLI deoA http://ecmdb.ca/proteins/P07650.xml Multifunctional protein surE P0A840 SURE_ECOLI surE http://ecmdb.ca/proteins/P0A840.xml 5'-nucleotidase yjjG P0A8Y1 YJJG_ECOLI yjjG http://ecmdb.ca/proteins/P0A8Y1.xml Class B acid phosphatase P0AE22 APHA_ECOLI aphA http://ecmdb.ca/proteins/P0AE22.xml Thymidine kinase P23331 KITH_ECOLI tdk http://ecmdb.ca/proteins/P23331.xml 5'-nucleotidase yfbR P76491 YFBR_ECOLI yfbR http://ecmdb.ca/proteins/P76491.xml Xanthosine permease P45562 XAPB_ECOLI xapB http://ecmdb.ca/proteins/P45562.xml Nucleoside permease nupC P0AFF2 NUPC_ECOLI nupC http://ecmdb.ca/proteins/P0AFF2.xml Nucleoside permease nupG P0AFF4 NUPG_ECOLI nupG http://ecmdb.ca/proteins/P0AFF4.xml Nucleoside permease nupX P33021 NUPX_ECOLI nupX http://ecmdb.ca/proteins/P33021.xml Outer membrane protein N P77747 OMPN_ECOLI ompN http://ecmdb.ca/proteins/P77747.xml Outer membrane pore protein E P02932 PHOE_ECOLI phoE http://ecmdb.ca/proteins/P02932.xml Outer membrane protein F P02931 OMPF_ECOLI ompF http://ecmdb.ca/proteins/P02931.xml Outer membrane protein C P06996 OMPC_ECOLI ompC http://ecmdb.ca/proteins/P06996.xml 5-Thymidylic acid + Water > Phosphate + Thymidine Adenosine triphosphate + Thymidine <> ADP + 5-Thymidylic acid + Hydrogen ion R01567 THYKI-RXN Phosphate + Thymidine <> Deoxyribose 1-phosphate + Thymine R01570 Adenosine triphosphate + Thymidine <> ADP + 5-Thymidylic acid R01567 5-Thymidylic acid + Water <> Thymidine + Phosphate R01569 Thymidine + Adenosine triphosphate > Hydrogen ion + 5-Thymidylic acid + ADP THYKI-RXN Thymidine + Phosphate <> deoxyribose-1-phosphate + Thymine THYM-PHOSPH-RXN Adenosine triphosphate + Thymidine > ADP + 5-Thymidylic acid Thymidine + Inorganic phosphate > Thymine + 2-deoxy-alpha-D-ribose 1-phosphate Deoxyribose 1-phosphate + Thymine > Phosphate + Thymidine PW_R006019 5 5-Thymidylic acid + Water > Phosphate + Thymidine