Orotic acid (PAMDB000094)

IdentificationTaxonomyPhysical PropertiesBiological PropertiesSpectraConcentrationsLinksReferencesEnzymes Transporters
Proteins (3280)
Record Information
Version 1.0
Update Date 1/22/2018 11:54:54 AM
Metabolite IDPAMDB000094
Identification
Name: Orotic acid
Description: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)
Structure
Thumb
🔍MOLSDFPDBSMILESInChIView Structure
Synonyms:
  • 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
Chemical Formula: C5H4N2O4
Average Molecular Weight: 156.0963
Monoisotopic Molecular Weight: 156.017106626
InChI Key: PXQPEWDEAKTCGB-UHFFFAOYSA-N
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)
CAS number: 65-86-1
IUPAC Name:2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid
Traditional IUPAC Name: orotic acid
SMILES:OC(=O)C1=CC(=O)NC(=O)N1
Chemical Taxonomy
Taxonomy DescriptionThis compound belongs to the class of organic compounds known as pyrimidinecarboxylic acids. These are pyrimidines with a structure containing a carboxyl group attached to the pyrimidine ring.
Kingdom Organic compounds
Super ClassOrganoheterocyclic compounds
Class Diazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct Parent Pyrimidinecarboxylic acids
Alternative Parents
Substituents
  • Pyrimidine-6-carboxylic acid
  • Hydropyrimidine carboxylic acid derivative
  • Pyrimidone
  • Hydropyrimidine
  • Heteroaromatic compound
  • Vinylogous amide
  • Urea
  • Lactam
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular Framework Aromatic heteromonocyclic compounds
External Descriptors
Physical Properties
State: Solid
Charge:-1
Melting point: 345.5 °C
Experimental Properties:
PropertyValueSource
Water Solubility:1.82 mg/mL at 18 oC [YALKOWSKY,SH & DANNENFELSER,RM (1992)]PhysProp
LogP:-0.83 [SANGSTER (1994)]PhysProp
Predicted Properties
PropertyValueSource
Water Solubility4.51 mg/mLALOGPS
logP-0.89ALOGPS
logP-1.2ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)2.83ChemAxon
pKa (Strongest Basic)-6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area95.5 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity33.27 m3·mol-1ChemAxon
Polarizability12.46 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Biological Properties
Cellular Locations: Cytoplasm
Reactions:
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
4,5-Dihydroorotic acid + Fumaric acid <> Orotic acid + Succinic acid
4,5-Dihydroorotic acid + a ubiquinone > Orotic acid + a ubiquinol
4,5-Dihydroorotic acid + a menaquinone > Orotic acid + a menaquinol
4,5-Dihydroorotic acid + Quinone <> Orotic acid + Hydroquinone
4,5-Dihydroorotic acid + Ubiquinone-1 + 4,5-Dihydroorotic acid > Ubiquinol-1 + Orotic acid
Orotic acid + Phosphoribosyl pyrophosphate > Pyrophosphate + Orotidylic acid
Pathways:
Spectra
Spectra:
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-0udi-1982000000-b20f2ec9a2f1acc84ae1View in MoNA
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-0zfr-2693000000-07bf11b5177412647d9bView in MoNA
GC-MSGC-MS Spectrum - GC-MSNot Available
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Negative (Annotated)splash10-03di-0900000000-81d73aed73c250fff3aeView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Negative (Annotated)splash10-0006-9300000000-ecb08d1854a2789480d1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Negative (Annotated)splash10-0006-9100000000-15748a4c13636c42f4f9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-02ti-4900000000-6fd6312d81f94faaaf11View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-03di-0900000000-1b7abf52e4a01cb85541View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0bt9-0900000000-1ad59feda583f2247b21View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-2900000000-0d0d27215e9f39a2a15bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9100000000-918a38777f5d4e049697View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-d7bbee7f2dc7bb0c6a83View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03dl-7900000000-303fe3e06e98f518a2eeView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-b2c02975bbba65c2f1c6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0bt9-0900000000-1ad59feda583f2247b21View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-2900000000-0d0d27215e9f39a2a15bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9100000000-918a38777f5d4e049697View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-d7bbee7f2dc7bb0c6a83View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03dl-7900000000-303fe3e06e98f518a2eeView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-b2c02975bbba65c2f1c6View in MoNA
MSMass Spectrum (Electron Ionization)splash10-066r-9300000000-e5c3ef3304f93a38628cView in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,1H] 2D NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
References
References:
  • 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. Pubmed: 10388475
  • Brosnan ME, Brosnan JT: Orotic acid excretion and arginine metabolism. J Nutr. 2007 Jun;137(6 Suppl 2):1656S-1661S. Pubmed: 17513443
  • Finkelstein JE, Hauser ER, Leonard CO, Brusilow SW: Late-onset ornithine transcarbamylase deficiency in male patients. J Pediatr. 1990 Dec;117(6):897-902. Pubmed: 2246687
  • Harris ML, Oberholzer VG: Conditions affecting the colorimetry of orotic acid and orotidine in urine. Clin Chem. 1980 Mar;26(3):473-9. Pubmed: 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. Pubmed: 6391739
  • 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. Pubmed: 22080510
  • 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. Pubmed: 21097882
  • 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. Pubmed: 262183
  • 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. Pubmed: 14770427
  • 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. Pubmed: 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. Pubmed: 11286382
  • 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. Pubmed: 2026685
  • 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. Pubmed: 8625455
  • 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. Pubmed: 15174800
  • 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. Pubmed: 17765195
  • van 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. Pubmed: 15375016
  • 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. Pubmed: 18402659
  • Visek WJ: Ammonia: its effects on biological systems, metabolic hormones, and reproduction. J Dairy Sci. 1984 Mar;67(3):481-98. Pubmed: 6371080
  • Visek WJ: Arginine and disease states. J Nutr. 1985 Apr;115(4):532-41. Pubmed: 3884753
  • 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. Pubmed: 18331064
  • Zieve L: Conditional deficiencies of ornithine or arginine. J Am Coll Nutr. 1986;5(2):167-76. Pubmed: 3088083
Synthesis Reference: 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.
Material Safety Data Sheet (MSDS) Download (PDF)
External Links:
ResourceLink
CHEBI ID16742
HMDB IDHMDB00226
Pubchem Compound ID967
Kegg IDC00295
ChemSpider ID942
WikipediaOrotic acid
BioCyc IDOROTATE
EcoCyc IDOROTATE
Ligand ExpoORO

Enzymes

Protein Details
• Dihydroorotate dehydrogenase
General function:
Involved in catalytic activity
Specific function:
(S)-dihydroorotate + a quinone = orotate + a quinol
Gene Name:
pyrD
Locus Tag:
PA3050
Molecular weight:
36.1 kDa
Reactions
(S)-dihydroorotate + a quinone = orotate + a quinol.
Protein Details
• Orotate phosphoribosyltransferase
General function:
Involved in orotate phosphoribosyltransferase activity
Specific function:
Catalyzes the transfer of a ribosyl phosphate group from 5-phosphoribose 1-diphosphate to orotate, leading to the formation of orotidine monophosphate (OMP)
Gene Name:
pyrE
Locus Tag:
PA5331
Molecular weight:
23.3 kDa
Reactions
Orotidine 5'-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate.

Transporters

Protein Details
• Aerobic C4-dicarboxylate transport protein
General function:
Involved in symporter activity
Specific function:
Responsible for the aerobic transport of the dicarboxylates fumarate, L- and D-malate and to a lesser extent succinate, from the periplasm across the inner membrane
Gene Name:
dctA
Locus Tag:
PA1183
Molecular weight:
46 kDa