2.02012-05-31 10:25:22 -06002015-09-13 12:56:07 -0600ECMDB00273M2MDB000114ThymidineThymidine 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)-pyrimidinedione1-(2-Deoxy-b-delta-erythro-pentofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione1-(2-Deoxy-b-δ-erythro-pentofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione1-(2-Deoxy-beta-delta-erythro-pentofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione1-(2-Deoxy-β-δ-erythro-pentofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione1-[4-Hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-pyrimidine-2,4-dione2'-Deoxy-5-methyl-Uridine2'-Deoxythymidine5-Methyl-2'-deoxyuridine5-MethyldeoxyuridineDeoxyribothymidineDeoxythymidineDTDThydThymidinThymidineThymine 2-desoxyribosideThymine deoxyribosideThymine-1 2-deoxy-b-D-RibofuranosideThymine-1 2-deoxy-b-delta-ribofuranosideThymine-1 2-deoxy-b-δ-ribofuranosideThymine-1 2-deoxy-beta-delta-RibofuranosideThymine-1 2-deoxy-β-δ-ribofuranosideC10H14N2O5242.2286242.0902715681-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dionethymidine50-89-5CC1=CN([C@H]2C[C@H](O)[C@@H](CO)O2)C(=O)NC1=OInChI=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/s1IQFYYKKMVGJFEH-XLPZGREQSA-NSolidCytosolExtra-organismPeriplasmlogp-1.32logs-0.56solubility6.68e+01 g/llogp-1.1pka_strongest_acidic9.96pka_strongest_basic-3iupac1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dioneaverage_mass242.2286mono_mass242.090271568smilesCC1=CN([C@H]2C[C@H](O)[C@@H](CO)O2)C(=O)NC1=OformulaC10H14N2O5inchiInChI=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/s1inchikeyIQFYYKKMVGJFEH-XLPZGREQSA-Npolar_surface_area99.1refractivity55.41polarizability23.06rotatable_bond_count2acceptor_count5donor_count3physiological_charge0formal_charge0Pyrimidine metabolismThe 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.PW000942ec00240MetabolicDrug metabolism - other enzymesec00983Metabolic pathwayseco01100pyrimidine deoxyribonucleosides degradationThe 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.PW002063Metabolicsalvage pathways of pyrimidine deoxyribonucleotidesThe 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 PW002061Metabolicsalvage pathways of pyrimidine deoxyribonucleotidesPWY0-181pyrimidine deoxyribonucleosides degradationPWY0-1298Specdb::CMs1960Specdb::CMs1993Specdb::CMs2811Specdb::CMs31112Specdb::CMs31113Specdb::CMs32286Specdb::CMs32329Specdb::CMs32330Specdb::CMs37397Specdb::CMs157927Specdb::CMs1056510Specdb::CMs1056512Specdb::CMs1056514Specdb::CMs1056516Specdb::CMs1056518Specdb::CMs1056519Specdb::CMs1056521Specdb::CMs1056523Specdb::CMs1056525Specdb::CMs1056527Specdb::CMs1056529Specdb::EiMs1979Specdb::NmrOneD1309Specdb::NmrOneD4904Specdb::NmrOneD4905Specdb::NmrOneD6382Specdb::NmrOneD6383Specdb::NmrOneD6384Specdb::NmrOneD6385Specdb::NmrOneD6386Specdb::NmrOneD6387Specdb::NmrOneD6388Specdb::NmrOneD6389Specdb::NmrOneD6390Specdb::NmrOneD6391Specdb::NmrOneD6392Specdb::NmrOneD6393Specdb::NmrOneD6394Specdb::NmrOneD6395Specdb::NmrOneD6396Specdb::NmrOneD6397Specdb::NmrOneD6398Specdb::NmrOneD6399Specdb::NmrOneD6400Specdb::NmrOneD6401Specdb::MsMs478Specdb::MsMs479Specdb::MsMs480Specdb::MsMs3904Specdb::MsMs3905Specdb::MsMs3906Specdb::MsMs3907Specdb::MsMs3908Specdb::MsMs3909Specdb::MsMs3910Specdb::MsMs3911Specdb::MsMs3912Specdb::MsMs3913Specdb::MsMs3914Specdb::MsMs3915Specdb::MsMs3916Specdb::MsMs3917Specdb::MsMs178890Specdb::MsMs178891Specdb::MsMs178892Specdb::MsMs181215Specdb::MsMs181216Specdb::MsMs181217Specdb::MsMs438495Specdb::MsMs438496Specdb::NmrTwoD1012Specdb::NmrTwoD1252HMDB0027357895585C0021417748THYMIDINETHMThymidineKeseler, 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-D590.21097882Kanehisa, 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-D114.22080510van 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 370:17-25.17765195Winder, 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 80:2939-2948.18331064Eells JT, Spector R: Purine and pyrimidine base and nucleoside concentrations in human cerebrospinal fluid and plasma. Neurochem Res. 1983 Nov;8(11):1451-7.6656991Zhao 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):1294-301.15709201Robins 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):2922-31.10561372Vogel 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):193-8.153886Schill WB, Miska W: Possible effects of the kallikrein-kinin system on male reproductive functions. Andrologia. 1992 Mar-Apr;24(2):69-75.1318646Grinlinton 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):982-7.8350335Schulz 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):1107-15.15234045Isoda 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):775-83.6485796Ashkenazi 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):961-5.2324546Abelson 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):208-16.6607976Svendsen 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):29-34.3111919Herdewijn, 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?1358896048Protein ushAP07024USHA_ECOLIushAhttp://ecmdb.ca/proteins/P07024.xmlThymidine phosphorylaseP07650TYPH_ECOLIdeoAhttp://ecmdb.ca/proteins/P07650.xmlMultifunctional protein surEP0A840SURE_ECOLIsurEhttp://ecmdb.ca/proteins/P0A840.xml5'-nucleotidase yjjGP0A8Y1YJJG_ECOLIyjjGhttp://ecmdb.ca/proteins/P0A8Y1.xmlClass B acid phosphataseP0AE22APHA_ECOLIaphAhttp://ecmdb.ca/proteins/P0AE22.xmlThymidine kinaseP23331KITH_ECOLItdkhttp://ecmdb.ca/proteins/P23331.xml5'-nucleotidase yfbRP76491YFBR_ECOLIyfbRhttp://ecmdb.ca/proteins/P76491.xmlXanthosine permeaseP45562XAPB_ECOLIxapBhttp://ecmdb.ca/proteins/P45562.xmlNucleoside permease nupCP0AFF2NUPC_ECOLInupChttp://ecmdb.ca/proteins/P0AFF2.xmlNucleoside permease nupGP0AFF4NUPG_ECOLInupGhttp://ecmdb.ca/proteins/P0AFF4.xmlNucleoside permease nupXP33021NUPX_ECOLInupXhttp://ecmdb.ca/proteins/P33021.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xml5-Thymidylic acid + Water > Phosphate + ThymidineAdenosine triphosphate + Thymidine <> ADP + 5-Thymidylic acid + Hydrogen ionR01567THYKI-RXNPhosphate + Thymidine <> Deoxyribose 1-phosphate + ThymineR01570Adenosine triphosphate + Thymidine <> ADP + 5-Thymidylic acidR015675-Thymidylic acid + Water <> Thymidine + PhosphateR01569Thymidine + Adenosine triphosphate > Hydrogen ion + 5-Thymidylic acid + ADPTHYKI-RXNThymidine + Phosphate <> deoxyribose-1-phosphate + ThymineTHYM-PHOSPH-RXNAdenosine triphosphate + Thymidine > ADP + 5-Thymidylic acidThymidine + Inorganic phosphate > Thymine + 2-deoxy-alpha-D-ribose 1-phosphateDeoxyribose 1-phosphate + Thymine > Phosphate + ThymidinePW_R0060195 5-Thymidylic acid + Water > Phosphate + Thymidine