2.0 2012-05-31 10:24:14 -0600 2015-09-13 12:56:07 -0600 ECMDB00226 M2MDB000094 Orotic acid Orotic acid is a heterocyclic compound and an acid; it is also known as pyrimidinecarboxylic acid. It was once believed to be part of the vitamin B complex and was called vitamin B13, but it is now known that it is not a vitamin but is instead manufactured in the body by intestinal flora. Orotic acid is converted to UMP by UMP synthase, a multifunctional protein with both orotate phosphoribosyltransferase and orotidylate decarboxylase activity. (Wikipedia) 1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidecarboxylate 1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidecarboxylic acid 1,2,3,6-Tetrahydro-2,6-dioxo-4-Pyrimidinecarboxylate 1,2,3,6-Tetrahydro-2,6-dioxo-4-Pyrimidinecarboxylic acid 1,2,3,6-Tetrahydro-2,6-dioxopyrimidin-4-carbonsaeure 2,6-Dihydroxy-4-pyrimidinecarboxylate 2,6-Dihydroxy-4-pyrimidinecarboxylic acid 2,6-Dihydroxypyrimidine-4-carboxylate 2,6-Dihydroxypyrimidine-4-carboxylic acid 2,6-Dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carboxylate 2,6-Dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carboxylic acid 2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylate 2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid 6-Carboxy-2,4-dihydroxypyrimidine 6-Carboxyuracil 6-Uracilcarboxylate 6-Uracilcarboxylic acid Acide orotique Acido orotico Acidum oroticum Animal galactose factor Lactinium Molkensaeure ORO Orodin Oropur Orotate Orotic acid Orotonin Orotonsan Orotsaeure Orotsaure Oroturic Orotyl Uracil-6-carbosaeure Uracil-6-carboxylate Uracil-6-carboxylic acid Vitamin B13 Whey factor C5H4N2O4 156.0963 156.017106626 2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid orotic acid 65-86-1 OC(=O)C1=CC(=O)NC(=O)N1 InChI=1S/C5H4N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h1H,(H,9,10)(H2,6,7,8,11) PXQPEWDEAKTCGB-UHFFFAOYSA-N Solid Cytosol Extra-organism Periplasm logp -0.89 ALOGPS logs -1.54 ALOGPS solubility 4.51e+00 g/l ALOGPS melting_point 345.5 oC logp -1.2 ChemAxon pka_strongest_acidic 2.83 ChemAxon pka_strongest_basic -6 ChemAxon iupac 2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid ChemAxon average_mass 156.0963 ChemAxon mono_mass 156.017106626 ChemAxon smiles OC(=O)C1=CC(=O)NC(=O)N1 ChemAxon formula C5H4N2O4 ChemAxon inchi InChI=1S/C5H4N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h1H,(H,9,10)(H2,6,7,8,11) ChemAxon inchikey PXQPEWDEAKTCGB-UHFFFAOYSA-N ChemAxon polar_surface_area 95.5 ChemAxon refractivity 33.27 ChemAxon polarizability 12.46 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 Drug metabolism - other enzymes ec00983 Metabolic pathways eco01100 uridine-5'-phosphate biosynthesis PWY-5686 Specdb::CMs 479 Specdb::CMs 1412 Specdb::CMs 3311 Specdb::CMs 30658 Specdb::CMs 31089 Specdb::CMs 32184 Specdb::CMs 37370 Specdb::CMs 170902 Specdb::CMs 1055103 Specdb::CMs 1055105 Specdb::CMs 1055107 Specdb::CMs 1055108 Specdb::CMs 1055110 Specdb::EiMs 1296 Specdb::NmrOneD 1238 Specdb::NmrOneD 2567 Specdb::NmrOneD 6172 Specdb::NmrOneD 6173 Specdb::NmrOneD 6174 Specdb::NmrOneD 6175 Specdb::NmrOneD 6176 Specdb::NmrOneD 6177 Specdb::NmrOneD 6178 Specdb::NmrOneD 6179 Specdb::NmrOneD 6180 Specdb::NmrOneD 6181 Specdb::NmrOneD 6182 Specdb::NmrOneD 6183 Specdb::NmrOneD 6184 Specdb::NmrOneD 6185 Specdb::NmrOneD 6186 Specdb::NmrOneD 6187 Specdb::NmrOneD 6188 Specdb::NmrOneD 6189 Specdb::NmrOneD 6190 Specdb::NmrOneD 6191 Specdb::MsMs 373 Specdb::MsMs 374 Specdb::MsMs 375 Specdb::MsMs 3675 Specdb::MsMs 3676 Specdb::MsMs 12911 Specdb::MsMs 12912 Specdb::MsMs 12913 Specdb::MsMs 19583 Specdb::MsMs 19584 Specdb::MsMs 19585 Specdb::MsMs 20765 Specdb::MsMs 20766 Specdb::MsMs 20767 Specdb::MsMs 22316 Specdb::MsMs 22317 Specdb::MsMs 22318 Specdb::MsMs 439097 Specdb::MsMs 440033 Specdb::MsMs 448052 Specdb::MsMs 2236372 Specdb::MsMs 2236420 Specdb::MsMs 2236946 Specdb::MsMs 2236994 Specdb::MsMs 2238481 Specdb::NmrTwoD 1000 Specdb::NmrTwoD 1221 HMDB00226 967 942 C00295 16742 OROTATE ORO Orotic 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 Vijayendran, C., Barsch, A., Friehs, K., Niehaus, K., Becker, A., Flaschel, E. (2008). "Perceiving molecular evolution processes in Escherichia coli by comprehensive metabolite and gene expression profiling." Genome Biol 9:R72. 18402659 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 Shoemaker JD, Elliott WH: Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease. J Chromatogr. 1991 Jan 2;562(1-2):125-38. 2026685 Zieve L: Conditional deficiencies of ornithine or arginine. J Am Coll Nutr. 1986;5(2):167-76. 3088083 Visek WJ: Ammonia: its effects on biological systems, metabolic hormones, and reproduction. J Dairy Sci. 1984 Mar;67(3):481-98. 6371080 Arranz JA, Riudor E, Rodes M, Roig M, Climent C, Rubio V, Sentis M, Burlina A: Optimization of allopurinol challenge: sample purification, protein intake control, and the use of orotidine response as a discriminative variable improve performance of the test for diagnosing ornithine carbamoyltransferase deficiency. Clin Chem. 1999 Jul;45(7):995-1001. 10388475 Sugio K, Gazdar AF, Albores-Saavedra J, Kokkinakis DM: High yields of K-ras mutations in intraductal papillary mucinous tumors and invasive adenocarcinomas induced by N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine in the pancreas of female Syrian hamsters. Carcinogenesis. 1996 Feb;17(2):303-9. 8625455 Finkelstein JE, Hauser ER, Leonard CO, Brusilow SW: Late-onset ornithine transcarbamylase deficiency in male patients. J Pediatr. 1990 Dec;117(6):897-902. 2246687 Harris ML, Oberholzer VG: Conditions affecting the colorimetry of orotic acid and orotidine in urine. Clin Chem. 1980 Mar;26(3):473-9. 7363468 Jakobs C, Sweetman L, Nyhan WL, Gruenke L, Craig JC, Wadman SK: Stable isotope dilution analysis of orotic acid and uracil in amniotic fluid. Clin Chim Acta. 1984 Nov 15;143(2):123-33. 6391739 Visek WJ: Arginine and disease states. J Nutr. 1985 Apr;115(4):532-41. 3884753 Mizutani Y, Wada H, Fukushima M, Yoshida O, Nakanishi H, Li YN, Miki T: Prognostic significance of orotate phosphoribosyltransferase activity in bladder carcinoma. Cancer. 2004 Feb 15;100(4):723-31. 14770427 Valik D, Sedova Z, Starha J, Zeman J, Hruba E, Dvorakova L: Acute hyperammonaemic encephalopathy in a female newborn caused by a novel, de novo mutation in the ornithine transcarbamylase gene. Acta Paediatr. 2004 May;93(5):710-1. 15174800 Mills GC, Schmalstieg FC, Newkirk KE, Goldblum RM: Cytosine and orotic acid in urine of immunodeficient children. Clin Chem. 1979 Mar;25(3):419-24. 262183 Paradis D, Giguere R, Auray-Blais C, Draper P, Lemieux B: An automated method for the determination of orotic acid in the urine of children being screened for metabolic disorders. Clin Biochem. 1980 Aug;13(4):160-3. 7449082 Potter M, Hammond JW, Sim KG, Green AK, Wilcken B: Ornithine carbamoyltransferase deficiency: improved sensitivity of testing for protein tolerance in the diagnosis of heterozygotes. J Inherit Metab Dis. 2001 Feb;24(1):5-14. 11286382 van Kuilenburg AB, van Lenthe H, Loffler M, van Gennip AH: Analysis of pyrimidine synthesis &quot;de novo&quot; intermediates in urine and dried urine filter- paper strips with HPLC-electrospray tandem mass spectrometry. Clin Chem. 2004 Nov;50(11):2117-24. Epub 2004 Sep 16. 15375016 Brosnan ME, Brosnan JT: Orotic acid excretion and arginine metabolism. J Nutr. 2007 Jun;137(6 Suppl 2):1656S-1661S. 17513443 Mitchell, Herschel K.; Nyc, Joseph F. Intermediates in the synthesis of orotic acid from oxalacetic ester and urea. Journal of the American Chemical Society (1947), 69 674-7. http://hmdb.ca/system/metabolites/msds/000/000/163/original/HMDB00226.pdf?1358462052 Dihydroorotate dehydrogenase P0A7E1 PYRD_ECOLI pyrD http://ecmdb.ca/proteins/P0A7E1.xml Orotate phosphoribosyltransferase P0A7E3 PYRE_ECOLI pyrE http://ecmdb.ca/proteins/P0A7E3.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 Aerobic C4-dicarboxylate transport protein P0A830 DCTA_ECOLI dctA http://ecmdb.ca/proteins/P0A830.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 4,5-Dihydroorotic acid + Ubiquinone-8 > Orotic acid + Ubiquinol-8 4,5-Dihydroorotic acid + Menaquinone 8 > Menaquinol 8 + Orotic acid Orotidylic acid + Pyrophosphate <> Orotic acid + Phosphoribosyl pyrophosphate R01870 OROPRIBTRANS-RXN 4,5-Dihydroorotic acid + Fumaric acid <> Orotic acid + Succinic acid R01867 4,5-Dihydroorotic acid + a ubiquinone > Orotic acid + a ubiquinol RXN0-6491 4,5-Dihydroorotic acid + a menaquinone > Orotic acid + a menaquinol RXN0-6554 (S)-dihydroorotate + a quinone > Orotic acid + a quinol Orotidylic acid + Pyrophosphate > Orotic acid + Phosphoribosyl pyrophosphate 4,5-Dihydroorotic acid + Quinone <> Orotic acid + Hydroquinone R01868 4,5-Dihydroorotic acid + Ubiquinone-1 + 4,5-Dihydroorotic acid > Ubiquinol-1 + Orotic acid PW_R003528 Orotic acid + Phosphoribosyl pyrophosphate > Pyrophosphate + Orotidylic acid PW_R003529 4 4,5-Dihydroorotic acid + Fumaric acid <> Orotic acid + Succinic acid 4 4,5-Dihydroorotic acid + Quinone <> Orotic acid + Hydroquinone Orotidylic acid + Pyrophosphate <> Orotic acid + Phosphoribosyl pyrophosphate 4 4,5-Dihydroorotic acid + Fumaric acid <> Orotic acid + Succinic acid Orotidylic acid + Pyrophosphate <> Orotic acid + Phosphoribosyl pyrophosphate