2.0 2012-05-31 10:27:15 -0600 2015-06-03 15:53:30 -0600 ECMDB00528 M2MDB000147 4,5-Dihydroorotic acid 4,5-Dihydroorotic acid is a substrate of the enzyme orotate reductase [EC 1.3.1.14], which is part of the pyrimidine metabolism pathway. (KEGG) Dihydroorotate is oxidized by Dihydroorotate dehydrogenases (DHODs) to orotate. These dehydrogenases use their FMN (flavin mononucleotide) prosthetic group to abstract a hydride equivalent from C6 to deprotonate C5 (+)-2,6-dioxo-hexahydro-pyrimidine-4-carboxylate (+)-2,6-dioxo-hexahydro-pyrimidine-4-carboxylic acid (S)-4,5-dihydroorotate (S)-4,5-dihydroorotic acid (S)-4-pyrimidinecarboxylic acid (S)-di-H-orotate (S)-hydroorotic acid (R)-2,6-dioxo-hexahydro-pyrimidine-4-carboxylate (R)-2,6-dioxo-hexahydro-pyrimidine-4-carboxylic acid (S)-2,6-dioxo-hexahydro-pyrimidine-4-carboxylate (S)-2,6-dioxo-hexahydro-pyrimidine-4-carboxylic acid (S)-4,5-Dihydroorotate (S)-4,5-dihydroorotic acid (S)-4-pyrimidinecarboxylate (S)-4-pyrimidinecarboxylic acid (S)-di-H-orotate (S)-di-H-orotic acid (S)-Dihydroorotate (S)-Dihydroorotic acid (S)-hydroorotate (S)-hydroorotic acid 2,6-dioxo-hexahydro-pyrimidine-4-carboxylate 2,6-dioxo-hexahydro-pyrimidine-4-carboxylic acid 4,5-Dihydro-L-orotate 4,5-Dihydro-L-orotic acid 4,5-Dihydroorotate 4,5-Dihydroorotic acid 5,6-Dihydroorotate 5,6-Dihydroorotic acid Dihydro-L-orotate Dihydro-L-orotic acid L-4,5-Dihydroorotate L-4,5-Dihydroorotic acid L-Dihydroorotate L-Dihydroorotic acid L-Hydroorotate L-Hydroorotic acid R,S-Hydroorotate R,S-Hydroorotic acid C5H6N2O4 158.1121 158.03275669 2,6-dioxo-1,3-diazinane-4-carboxylic acid dihydroorotic acid 155-54-4 OC(=O)C1CC(=O)NC(=O)N1 InChI=1S/C5H6N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h2H,1H2,(H,9,10)(H2,6,7,8,11) UFIVEPVSAGBUSI-UHFFFAOYSA-N Solid Cytosol logp -1.70 ALOGPS logs -1.10 ALOGPS solubility 1.27e+01 g/l ALOGPS logp -1.5 ChemAxon pka_strongest_acidic 3.28 ChemAxon pka_strongest_basic -8.2 ChemAxon iupac 2,6-dioxo-1,3-diazinane-4-carboxylic acid ChemAxon average_mass 158.1121 ChemAxon mono_mass 158.03275669 ChemAxon smiles OC(=O)C1CC(=O)NC(=O)N1 ChemAxon formula C5H6N2O4 ChemAxon inchi InChI=1S/C5H6N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h2H,1H2,(H,9,10)(H2,6,7,8,11) ChemAxon inchikey UFIVEPVSAGBUSI-UHFFFAOYSA-N ChemAxon polar_surface_area 95.5 ChemAxon refractivity 31.58 ChemAxon polarizability 13.09 ChemAxon rotatable_bond_count 1 ChemAxon acceptor_count 4 ChemAxon donor_count 3 ChemAxon physiological_charge -1 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 Metabolic pathways eco01100 uridine-5'-phosphate biosynthesis PWY-5686 Specdb::CMs 3068 Specdb::CMs 37598 Specdb::CMs 161353 Specdb::CMs 1065092 Specdb::CMs 1065094 Specdb::CMs 1065096 Specdb::CMs 1065098 Specdb::CMs 1065100 Specdb::NmrOneD 1406 Specdb::NmrOneD 144210 Specdb::NmrOneD 144211 Specdb::NmrOneD 144212 Specdb::NmrOneD 144213 Specdb::NmrOneD 144214 Specdb::NmrOneD 144215 Specdb::NmrOneD 144216 Specdb::NmrOneD 144217 Specdb::NmrOneD 144218 Specdb::NmrOneD 144219 Specdb::NmrOneD 144220 Specdb::NmrOneD 144221 Specdb::NmrOneD 144222 Specdb::NmrOneD 144223 Specdb::NmrOneD 144224 Specdb::NmrOneD 144225 Specdb::NmrOneD 144226 Specdb::NmrOneD 144227 Specdb::NmrOneD 144228 Specdb::NmrOneD 144229 Specdb::MsMs 746 Specdb::MsMs 747 Specdb::MsMs 748 Specdb::MsMs 182814 Specdb::MsMs 182815 Specdb::MsMs 182816 Specdb::MsMs 183162 Specdb::MsMs 183163 Specdb::MsMs 183164 Specdb::MsMs 2837022 Specdb::MsMs 2837023 Specdb::MsMs 2837024 Specdb::MsMs 2868024 Specdb::MsMs 2868025 Specdb::MsMs 2868026 Specdb::NmrTwoD 1350 HMDB00528 648 628 C00337 30865 DI-H-OROTATE 4,5-Dihydroorotic acid 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 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. 19212411 Burger, Klaus; Neuhauser, Horst; Rudolph, Martin. A new, preparatively simple way to dihydroorotic acid, 1-methyl-4,5-dihydroorotic acid and their derivatives. Chemiker-Zeitung (1990), 114(7-8), 251-5. Dihydroorotase P05020 PYRC_ECOLI pyrC http://ecmdb.ca/proteins/P05020.xml Dihydroorotate dehydrogenase P0A7E1 PYRD_ECOLI pyrD http://ecmdb.ca/proteins/P0A7E1.xml 4,5-Dihydroorotic acid + Ubiquinone-8 > Orotic acid + Ubiquinol-8 4,5-Dihydroorotic acid + Menaquinone 8 > Menaquinol 8 + Orotic acid 4,5-Dihydroorotic acid + Water <> Ureidosuccinic acid + Hydrogen ion R01993 DIHYDROOROT-RXN 4,5-Dihydroorotic acid + Fumaric acid <> Orotic acid + Succinic acid R01867 4,5-Dihydroorotic acid + Water <> Ureidosuccinic acid R01993 4,5-Dihydroorotic acid + a ubiquinone > Orotic acid + a ubiquinol RXN0-6491 4,5-Dihydroorotic acid + a menaquinone > Orotic acid + a menaquinol RXN0-6554 4,5-Dihydroorotic acid + Quinone <> Orotic acid + Hydroquinone R01868 N-carbamoyl-L-aspartate + Hydrogen ion > Water + 4,5-Dihydroorotic acid + 4,5-Dihydroorotic acid PW_R003527 4,5-Dihydroorotic acid + Ubiquinone-1 + 4,5-Dihydroorotic acid > Ubiquinol-1 + Orotic acid PW_R003528 4 4,5-Dihydroorotic acid + Fumaric acid <> Orotic acid + Succinic acid 4 4,5-Dihydroorotic acid + Quinone <> Orotic acid + Hydroquinone 4 4,5-Dihydroorotic acid + Water <> Ureidosuccinic acid + Hydrogen ion 4 4,5-Dihydroorotic acid + Fumaric acid <> Orotic acid + Succinic acid Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glucose Shake flask and filter culture 11.9 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 47600 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glycerol Shake flask and filter culture 4.58 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 18320 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L acetate Shake flask and filter culture 3.59 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 14360 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621