2.02012-05-31 10:24:14 -06002015-09-13 12:56:07 -0600ECMDB00226M2MDB000094Orotic acidOrotic 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-pyrimidecarboxylate1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidecarboxylic acid1,2,3,6-Tetrahydro-2,6-dioxo-4-Pyrimidinecarboxylate1,2,3,6-Tetrahydro-2,6-dioxo-4-Pyrimidinecarboxylic acid1,2,3,6-Tetrahydro-2,6-dioxopyrimidin-4-carbonsaeure2,6-Dihydroxy-4-pyrimidinecarboxylate2,6-Dihydroxy-4-pyrimidinecarboxylic acid2,6-Dihydroxypyrimidine-4-carboxylate2,6-Dihydroxypyrimidine-4-carboxylic acid2,6-Dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carboxylate2,6-Dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carboxylic acid2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylate2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid6-Carboxy-2,4-dihydroxypyrimidine6-Carboxyuracil6-Uracilcarboxylate6-Uracilcarboxylic acidAcide orotiqueAcido oroticoAcidum oroticumAnimal galactose factorLactiniumMolkensaeureOROOrodinOropurOrotateOrotic acidOrotoninOrotonsanOrotsaeureOrotsaureOroturicOrotylUracil-6-carbosaeureUracil-6-carboxylateUracil-6-carboxylic acidVitamin B13Whey factorC5H4N2O4156.0963156.0171066262,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acidorotic acid65-86-1OC(=O)C1=CC(=O)NC(=O)N1InChI=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-NSolidCytosolExtra-organismPeriplasmlogp-0.89logs-1.54solubility4.51e+00 g/lmelting_point345.5 oClogp-1.2pka_strongest_acidic2.83pka_strongest_basic-6iupac2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acidaverage_mass156.0963mono_mass156.017106626smilesOC(=O)C1=CC(=O)NC(=O)N1formulaC5H4N2O4inchiInChI=1S/C5H4N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h1H,(H,9,10)(H2,6,7,8,11)inchikeyPXQPEWDEAKTCGB-UHFFFAOYSA-Npolar_surface_area95.5refractivity33.27polarizability12.46rotatable_bond_count1acceptor_count4donor_count3physiological_charge-1formal_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 pathwayseco01100uridine-5'-phosphate biosynthesisPWY-5686Specdb::CMs479Specdb::CMs1412Specdb::CMs3311Specdb::CMs30658Specdb::CMs31089Specdb::CMs32184Specdb::CMs37370Specdb::CMs170902Specdb::CMs1055103Specdb::CMs1055105Specdb::CMs1055107Specdb::CMs1055108Specdb::CMs1055110Specdb::EiMs1296Specdb::NmrOneD1238Specdb::NmrOneD2567Specdb::NmrOneD6172Specdb::NmrOneD6173Specdb::NmrOneD6174Specdb::NmrOneD6175Specdb::NmrOneD6176Specdb::NmrOneD6177Specdb::NmrOneD6178Specdb::NmrOneD6179Specdb::NmrOneD6180Specdb::NmrOneD6181Specdb::NmrOneD6182Specdb::NmrOneD6183Specdb::NmrOneD6184Specdb::NmrOneD6185Specdb::NmrOneD6186Specdb::NmrOneD6187Specdb::NmrOneD6188Specdb::NmrOneD6189Specdb::NmrOneD6190Specdb::NmrOneD6191Specdb::MsMs373Specdb::MsMs374Specdb::MsMs375Specdb::MsMs3675Specdb::MsMs3676Specdb::MsMs12911Specdb::MsMs12912Specdb::MsMs12913Specdb::MsMs19583Specdb::MsMs19584Specdb::MsMs19585Specdb::MsMs20765Specdb::MsMs20766Specdb::MsMs20767Specdb::MsMs22316Specdb::MsMs22317Specdb::MsMs22318Specdb::MsMs439097Specdb::MsMs440033Specdb::MsMs448052Specdb::MsMs2236372Specdb::MsMs2236420Specdb::MsMs2236946Specdb::MsMs2236994Specdb::MsMs2238481Specdb::NmrTwoD1000Specdb::NmrTwoD1221HMDB00226967942C0029516742OROTATEOROOrotic acidKeseler, 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-D114.22080510Vijayendran, 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:R72.18402659van 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 80:2939-2948.18331064Shoemaker 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):125-38.2026685Zieve L: Conditional deficiencies of ornithine or arginine. J Am Coll Nutr. 1986;5(2):167-76.3088083Visek WJ: Ammonia: its effects on biological systems, metabolic hormones, and reproduction. J Dairy Sci. 1984 Mar;67(3):481-98.6371080Arranz 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):995-1001.10388475Sugio 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):303-9.8625455Finkelstein JE, Hauser ER, Leonard CO, Brusilow SW: Late-onset ornithine transcarbamylase deficiency in male patients. J Pediatr. 1990 Dec;117(6):897-902.2246687Harris ML, Oberholzer VG: Conditions affecting the colorimetry of orotic acid and orotidine in urine. Clin Chem. 1980 Mar;26(3):473-9.7363468Jakobs 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):123-33.6391739Visek WJ: Arginine and disease states. J Nutr. 1985 Apr;115(4):532-41.3884753Mizutani 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):723-31.14770427Valik 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):710-1.15174800Mills GC, Schmalstieg FC, Newkirk KE, Goldblum RM: Cytosine and orotic acid in urine of immunodeficient children. Clin Chem. 1979 Mar;25(3):419-24.262183Paradis 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):160-3.7449082Potter 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):5-14.11286382van Kuilenburg AB, van Lenthe H, Loffler M, van Gennip AH: Analysis of pyrimidine synthesis "de novo" 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 16.15375016Brosnan ME, Brosnan JT: Orotic acid excretion and arginine metabolism. J Nutr. 2007 Jun;137(6 Suppl 2):1656S-1661S.17513443Mitchell, 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?1358462052Dihydroorotate dehydrogenaseP0A7E1PYRD_ECOLIpyrDhttp://ecmdb.ca/proteins/P0A7E1.xmlOrotate phosphoribosyltransferaseP0A7E3PYRE_ECOLIpyrEhttp://ecmdb.ca/proteins/P0A7E3.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlAerobic C4-dicarboxylate transport proteinP0A830DCTA_ECOLIdctAhttp://ecmdb.ca/proteins/P0A830.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xml4,5-Dihydroorotic acid + Ubiquinone-8 > Orotic acid + Ubiquinol-84,5-Dihydroorotic acid + Menaquinone 8 > Menaquinol 8 + Orotic acidOrotidylic acid + Pyrophosphate <> Orotic acid + Phosphoribosyl pyrophosphateR01870OROPRIBTRANS-RXN4,5-Dihydroorotic acid + Fumaric acid <> Orotic acid + Succinic acidR018674,5-Dihydroorotic acid + a ubiquinone > Orotic acid + a ubiquinolRXN0-64914,5-Dihydroorotic acid + a menaquinone > Orotic acid + a menaquinolRXN0-6554(S)-dihydroorotate + a quinone > Orotic acid + a quinolOrotidylic acid + Pyrophosphate > Orotic acid + Phosphoribosyl pyrophosphate4,5-Dihydroorotic acid + Quinone <> Orotic acid + HydroquinoneR01868 4,5-Dihydroorotic acid + Ubiquinone-1 + 4,5-Dihydroorotic acid > Ubiquinol-1 + Orotic acidPW_R003528Orotic acid + Phosphoribosyl pyrophosphate > Pyrophosphate + Orotidylic acidPW_R0035294 4,5-Dihydroorotic acid + Fumaric acid <> Orotic acid + Succinic acid4 4,5-Dihydroorotic acid + Quinone <> Orotic acid + HydroquinoneOrotidylic acid + Pyrophosphate <> Orotic acid + Phosphoribosyl pyrophosphate4 4,5-Dihydroorotic acid + Fumaric acid <> Orotic acid + Succinic acidOrotidylic acid + Pyrophosphate <> Orotic acid + Phosphoribosyl pyrophosphate