2.02012-05-31 13:52:00 -06002015-09-13 12:56:11 -0600ECMDB01409M2MDB000375dUMPdUMP is formed by the reduction of ribonucleotides to deoxyribonucleotides by ribonucleoside diphosphate reductase [EC 1.17.4.1]. dUMP by the action of by thymidylate synthetase [EC 2.1.1.45] produces dTMP (5,10-Methylene-5,6,7,8-tetrahydrofolate is a cofactor for the reaction). The nuclear form of uracil-DNA glycosylase (UNG2), that its major role is to remove misincorporated dUMP residues (cells deficient in removal of misincorporated dUMP accumulate uracil residues). (PMID 11554311)2'-Deoxy-5'-uridylate2'-Deoxy-5'-uridylic acid2'-Deoxyuridine 5'-monophosphate2'-Deoxyuridine 5'-monophosphoric acid2'-Deoxyuridine 5'-phosphate2'-Deoxyuridine 5'-phosphoric acid2'-Deoxyuridine-5'-phosphate2'-Deoxyuridine-5'-phosphoric acid2'-Deoxyuridine-5-monophosphate2'-Deoxyuridine-5-monophosphoric acid2'-Deoxyuridylate2'-Deoxyuridylic acidDeoxy-UMPDeoxyurdine-phosphateDeoxyurdine-phosphoric acidDeoxyuridine 5'-monophosphateDeoxyuridine 5'-monophosphoric acidDeoxyuridine 5'-phosphateDeoxyuridine 5'-phosphoric acidDeoxyuridine monophosphateDeoxyuridine monophosphoric acidDeoxyuridine-phosphateDeoxyuridine-phosphoric acidDeoxyuridylateDeoxyuridylic acidDUMPUC9H13N2O8P308.1819308.040951914{[(2R,3S,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy}phosphonic acid2'-deoxyuridylic acid964-26-1O[C@H]1C[C@@H](O[C@@H]1COP(O)(O)=O)N1C=CC(=O)NC1=OInChI=1S/C9H13N2O8P/c12-5-3-8(11-2-1-7(13)10-9(11)14)19-6(5)4-18-20(15,16)17/h1-2,5-6,8,12H,3-4H2,(H,10,13,14)(H2,15,16,17)/t5-,6+,8+/m0/s1JSRLJPSBLDHEIO-SHYZEUOFSA-NSolidCytosolExtra-organismPeriplasmlogp-1.42logs-1.59solubility7.97e+00 g/llogp-1.6pka_strongest_acidic1.23pka_strongest_basic-3.2iupac{[(2R,3S,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy}phosphonic acidaverage_mass308.1819mono_mass308.040951914smilesO[C@H]1C[C@@H](O[C@@H]1COP(O)(O)=O)N1C=CC(=O)NC1=OformulaC9H13N2O8PinchiInChI=1S/C9H13N2O8P/c12-5-3-8(11-2-1-7(13)10-9(11)14)19-6(5)4-18-20(15,16)17/h1-2,5-6,8,12H,3-4H2,(H,10,13,14)(H2,15,16,17)/t5-,6+,8+/m0/s1inchikeyJSRLJPSBLDHEIO-SHYZEUOFSA-Npolar_surface_area145.63refractivity61.93polarizability25.86rotatable_bond_count4acceptor_count7donor_count4physiological_charge-2formal_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.PW000942ec00240MetabolicOne carbon pool by folateDihydrofolic acid, a product of the folate biosynthesis pathway, can be metabolized by multiple enzymes.
Dihydrofolic acid can be reduced by a NADP-driven dihydrofolate reductase resulting in a NADPH, hydrogen ion and folic acid.
Dihydrofolic acid can also be reduced by an NADPH-driven dihydrofolate reductase resulting in a NADP and a tetrahydrofolic acid. Folic acid can also produce a tetrahydrofolic acid through a NADPH-driven dihydrofolate reductase.
Dihydrofolic acid also interacts with 5-thymidylic acid through a thymidylate synthase resulting in the release of dUMP and 5,10-methylene-THF
Tetrahydrofolic acid can be converted into 5,10-methylene-THF through two different reversible reactions.
Tetrahydrofolic acid interacts with a S-Aminomethyldihydrolipoylprotein through a aminomethyltransferase resulting in the release of ammonia, a dihydrolipoylprotein and 5,10-Methylene-THF
Tetrahydrofolic acid interacts with L-serine through a glycine hydroxymethyltransferase resulting in a glycine, water and 5,10-Methylene-THF.
The compound 5,10-methylene-THF reacts with an NADPH dependent methylenetetrahydrofolate reductase [NAD(P)H] resulting in NADP and 5-Methyltetrahydrofolic acid. This compound interacts with homocysteine through a methionine synthase resulting in L-methionine and tetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 10-formyltetrahydrofolate through 4 different enzymes:
1.- Tetrahydrofolic acid interacts with FAICAR through a phosphoribosylaminoimidazolecarboxamide formyltransferase resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide and a 10-formyltetrahydrofolate
2.-Tetrahydrofolic acid interacts with 5'-Phosphoribosyl-N-formylglycinamide through a phosphoribosylglycinamide formyltransferase 2 resulting in a Glycineamideribotide and a 10-formyltetrahydrofolate
3.-Tetrahydrofolic acid interacts with Formic acid through a formyltetrahydrofolate hydrolase resulting in water and a 10-formyltetrahydrofolate
4.-Tetrahydrofolic acid interacts with N-formylmethionyl-tRNA(fMet) through a 10-formyltetrahydrofolate:L-methionyl-tRNA(fMet) N-formyltransferase resulting in a L-methionyl-tRNA(Met) and a 10-formyltetrahydrofolate
10-formyltetrahydrofolate can interact with a hydrogen ion through a bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in water and
5,10-methenyltetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 5,10-methenyltetrahydrofolic acid by reacting with a
5'-phosphoribosyl-a-N-formylglycineamidine through a phosphoribosylglycinamide formyltransferase 2 resulting in water, glycineamideribotide and 5,10-methenyltetrahydrofolic acid. The latter compound can either interact with water through an aminomethyltransferase resulting in a N5-Formyl-THF, or it can interact with a NADPH driven bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in a NADP and 5,10-Methylene THF.
PW000773ec00670MetabolicMetabolic pathwayseco01100One Carbon Pool by Folate IDihydrofolic acid, a product of the folate biosynthesis pathway, can be metabolized by multiple enzymes.
Dihydrofolic acid can be reduced by a NADP-driven dihydrofolate reductase resulting in a NADPH, hydrogen ion and folic acid.
Dihydrofolic acid can also be reduced by an NADPH-driven dihydrofolate reductase resulting in a NADP and a tetrahydrofolic acid. Folic acid can also produce a tetrahydrofolic acid through a NADPH-driven dihydrofolate reductase.
Dihydrofolic acid also interacts with 5-thymidylic acid through a thymidylate synthase resulting in the release of dUMP and 5,10-methylene-THF
Tetrahydrofolic acid can be converted into 5,10-methylene-THF through two different reversible reactions.
Tetrahydrofolic acid interacts with a S-Aminomethyldihydrolipoylprotein through a aminomethyltransferase resulting in the release of ammonia, a dihydrolipoylprotein and 5,10-Methylene-THF
Tetrahydrofolic acid interacts with L-serine through a glycine hydroxymethyltransferase resulting in a glycine, water and 5,10-Methylene-THF.
The compound 5,10-methylene-THF reacts with an NADPH dependent methylenetetrahydrofolate reductase [NAD(P)H] resulting in NADP and 5-Methyltetrahydrofolic acid. This compound interacts with homocysteine through a methionine synthase resulting in L-methionine and tetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 10-formyltetrahydrofolate through 4 different enzymes:
1.- Tetrahydrofolic acid interacts with FAICAR through a phosphoribosylaminoimidazolecarboxamide formyltransferase resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide and a 10-formyltetrahydrofolate
2.-Tetrahydrofolic acid interacts with 5'-Phosphoribosyl-N-formylglycinamide through a phosphoribosylglycinamide formyltransferase 2 resulting in a Glycineamideribotide and a 10-formyltetrahydrofolate
3.-Tetrahydrofolic acid interacts with Formic acid through a formyltetrahydrofolate hydrolase resulting in water and a 10-formyltetrahydrofolate
4.-Tetrahydrofolic acid interacts with N-formylmethionyl-tRNA(fMet) through a 10-formyltetrahydrofolate:L-methionyl-tRNA(fMet) N-formyltransferase resulting in a L-methionyl-tRNA(Met) and a 10-formyltetrahydrofolate
10-formyltetrahydrofolate can interact with a hydrogen ion through a bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in water and
5,10-methenyltetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 5,10-methenyltetrahydrofolic acid by reacting with a
5'-phosphoribosyl-a-N-formylglycineamidine through a phosphoribosylglycinamide formyltransferase 2 resulting in water, glycineamideribotide and 5,10-methenyltetrahydrofolic acid. The latter compound can either interact with water through an aminomethyltransferase resulting in a N5-Formyl-THF, or it can interact with a NADPH driven bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in a NADP and 5,10-Methylene THF.
PW001735Metabolicsalvage 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 deoxyribonucleotidesPWY0-181formylTHF biosynthesis I1CMET2-PWYpyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis IPWY0-166Specdb::CMs2436Specdb::CMs38059Specdb::CMs137674Specdb::CMs145408Specdb::NmrOneD1701Specdb::NmrOneD95958Specdb::NmrOneD95959Specdb::NmrOneD95960Specdb::NmrOneD95961Specdb::NmrOneD95962Specdb::NmrOneD95963Specdb::NmrOneD95964Specdb::NmrOneD95965Specdb::NmrOneD95966Specdb::NmrOneD95967Specdb::NmrOneD95968Specdb::NmrOneD95969Specdb::NmrOneD95970Specdb::NmrOneD95971Specdb::NmrOneD95972Specdb::NmrOneD95973Specdb::NmrOneD95974Specdb::NmrOneD95975Specdb::NmrOneD95976Specdb::NmrOneD95977Specdb::MsMs1562Specdb::MsMs1563Specdb::MsMs1564Specdb::MsMs5285Specdb::MsMs178140Specdb::MsMs178141Specdb::MsMs178142Specdb::MsMs180456Specdb::MsMs180457Specdb::MsMs180458Specdb::MsMs439046Specdb::MsMs1470864Specdb::MsMs1470900Specdb::MsMs1470901Specdb::MsMs1470902Specdb::MsMs2236310Specdb::MsMs2237054Specdb::MsMs2238477Specdb::MsMs2239122Specdb::MsMs2240567Specdb::MsMs2241119Specdb::MsMs2242636Specdb::MsMs2243238Specdb::MsMs2244330Specdb::MsMs2245759Specdb::NmrTwoD1642HMDB014096506358574C0036517622DUMPUMPdUMPKeseler, 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 370:17-25.17765195Krokan, H. E., Otterlei, M., Nilsen, H., Kavli, B., Skorpen, F., Andersen, S., Skjelbred, C., Akbari, M., Aas, P. A., Slupphaug, G. (2001). "Properties and functions of human uracil-DNA glycosylase from the UNG gene." Prog Nucleic Acid Res Mol Biol 68:365-386.11554311Richards RG, Sowers LC, Laszlo J, Sedwick WD: The occurrence and consequences of deoxyuridine in DNA. Adv Enzyme Regul. 1984;22:157-85.6147963http://hmdb.ca/system/metabolites/msds/000/001/271/original/HMDB01409.pdf?1358461795Deoxyuridine 5'-triphosphate nucleotidohydrolaseP06968DUT_ECOLIduthttp://ecmdb.ca/proteins/P06968.xmlProtein ushAP07024USHA_ECOLIushAhttp://ecmdb.ca/proteins/P07024.xmlThymidylate kinaseP0A720KTHY_ECOLItmkhttp://ecmdb.ca/proteins/P0A720.xmlMultifunctional protein surEP0A840SURE_ECOLIsurEhttp://ecmdb.ca/proteins/P0A840.xmlThymidylate synthaseP0A884TYSY_ECOLIthyAhttp://ecmdb.ca/proteins/P0A884.xml5'-nucleotidase yjjGP0A8Y1YJJG_ECOLIyjjGhttp://ecmdb.ca/proteins/P0A8Y1.xmlClass B acid phosphataseP0AE22APHA_ECOLIaphAhttp://ecmdb.ca/proteins/P0AE22.xmlProtein mazGP0AEY3MAZG_ECOLImazGhttp://ecmdb.ca/proteins/P0AEY3.xmlThymidine kinaseP23331KITH_ECOLItdkhttp://ecmdb.ca/proteins/P23331.xmlNucleoside triphosphatase nudIP52006NUDI_ECOLInudIhttp://ecmdb.ca/proteins/P52006.xmlNucleoside-triphosphatase rdgBP52061RDGB_ECOLIrdgBhttp://ecmdb.ca/proteins/P52061.xml5'-nucleotidase yfbRP76491YFBR_ECOLIyfbRhttp://ecmdb.ca/proteins/P76491.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.xmldUMP + Water > Deoxyuridine + PhosphateDeoxyuridine triphosphate + Water <> dUMP + Hydrogen ion + PyrophosphateR02100DUTP-PYROP-RXNAdenosine triphosphate + Deoxyuridine > ADP + dUMP + Hydrogen ionR02099DURIDKI-RXNdUMP + 5,10-Methylene-THF <> Dihydrofolic acid + 5-Thymidylic acidR02101THYMIDYLATESYN-RXNAdenosine triphosphate + dUMP <> ADP + dUDPR02098Adenosine triphosphate + Deoxyuridine <> ADP + dUMPR02099Deoxyuridine triphosphate + Water <> dUMP + PyrophosphateR02100Deoxyuridine triphosphate + Water > Hydrogen ion + dUMP + PyrophosphateDUTP-PYROP-RXNdUMP + 5,10-Methylene-THF > 5-Thymidylic acid + Dihydrofolic acidTHYMIDYLATESYN-RXNDeoxyuridine triphosphate + Water > dUMP + PyrophosphateDihydrofolic acid + 5-Thymidylic acid + Dihydrofolic acid > 5,10-Methylene-THF + dUMP + 5,10-Methylene-THFPW_R002540dUMP + 5,10-methenyltetrahydrofolate mono-L-glutamate + 5,10-methenyltetrahydrofolate mono-L-glutamate > Dihydrofolic acid + 5-Thymidylic acid + Dihydrofolic acidPW_R003540Deoxyuridine triphosphate + Water > Phosphate + Hydrogen ion + dUMPPW_R003539dUMP + 5 5,10-Methylene-THF <> Dihydrofolic acid +5 5-Thymidylic acidAdenosine triphosphate + dUMP <> ADP + dUDPDeoxyuridine triphosphate + Water <> dUMP + Hydrogen ion + PyrophosphatedUMP + 5 5,10-Methylene-THF <> Dihydrofolic acid +5 5-Thymidylic acidDeoxyuridine triphosphate + Water <> dUMP + Hydrogen ion + Pyrophosphate