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Record Information
Version4.0
Creation Date2005-11-16 15:48:42 UTC
Update Date2017-09-27 07:32:38 UTC
HMDB IDHMDB0000226
Secondary Accession Numbers
  • HMDB00226
Metabolite Identification
Common NameOrotic acid
DescriptionOrotic acid is a minor dietary constituent. Indeed, until it was realized that it could be synthesized by humans, orotic acid was known as vitamin B-13. The richest dietary sources are cow's milk and other dairy products as well as root vegetables such as carrots and beets. Dietary intake probably contributes to a basal rate of orotic acid excretion in urine because fasting decreases excretion by ~50%. However, it is now apparent that most urinary orotic acid is synthesized in the body, where it arises as an intermediate in the pathway for the synthesis of pyrimidine nucleotides. Orotic acid is converted to UMP by UMP synthase, a multifunctional protein with both orotate phosphoribosyltransferase and orotidylate decarboxylase activity. The most frequently observed inborn error of pyrimidine nucleotide synthesis is a mutation of the multifunctional protein UMP synthase. This disorder prevents the conversion of orotic acid to UMP and thus to other pyrimidines. As a result, plasma orotic acid accumulates to high concentrations, and increased quantities appear in the urine. Indeed, urinary orotic acid is so markedly increased in individuals harboring a mutation in UMP synthase that orotic acid crystals can form in the urine. The urinary concentration of orotic acid in homozygotes can be of the order of millimoles per millimole creatinine. By comparison, the urinary level in unaffected individuals is ~ 1 umol/mmol creatinine. (PMID: 17513443 ).
Structure
Thumb
Synonyms
ValueSource
OrotsaeureChEBI
Uracil-6-carboxylic acidChEBI
OrotateGenerator
Uracil-6-carboxylateGenerator
1,2,3,6-tetrahydro-2,6-dioxo-4-Pyrimidecarboxylic acidHMDB
1,2,3,6-tetrahydro-2,6-dioxo-4-Pyrimidinecarboxylic acidHMDB
1,2,3,6-tetrahydro-2,6-Dioxopyrimidin-4-carbonsaeureHMDB
2,6-Dihydroxy-4-pyrimidinecarboxylic acidHMDB
2,6-Dihydroxypyrimidine-4-carboxylic acidHMDB
2,6-dioxo-1,2,3,6-tetrahydro-Pyrimidine-4-carboxylic acidHMDB
2,6-dioxo-1,2,3,6-Tetrahydropyrimidine-4-carboxylic acidHMDB
6-Carboxy-2,4-dihydroxypyrimidineHMDB
6-CarboxyuracilHMDB
6-Uracilcarboxylic acidHMDB
Acide orotiqueHMDB
acido OroticoHMDB
Acidum oroticumHMDB
Animal galactose factorHMDB
LactiniumHMDB
MolkensaeureHMDB
OROHMDB
OrodinHMDB
OropurHMDB
OrotoninHMDB
OrotonsanHMDB
OrotsaureHMDB
OroturicHMDB
OrotylHMDB
Uracil-6-carbosaeureHMDB
Vitamin b13HMDB
Whey factorHMDB
Zinc orotateMeSH
Orotate, zincMeSH
Acid, oroticMeSH
Orotate, potassiumMeSH
Potassium orotateMeSH
Orotate, sodiumMeSH
Sodium orotateMeSH
Chemical FormulaC5H4N2O4
Average Molecular Weight156.0963
Monoisotopic Molecular Weight156.017106626
IUPAC Name2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid
Traditional Nameorotic acid
CAS Registry Number65-86-1
SMILES
OC(=O)C1=CC(=O)NC(=O)N1
InChI Identifier
InChI=1S/C5H4N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h1H,(H,9,10)(H2,6,7,8,11)
InChI KeyPXQPEWDEAKTCGB-UHFFFAOYSA-N
Chemical 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentPyrimidinecarboxylic acids
Alternative Parents
Substituents
  • Hydropyrimidine carboxylic acid derivative
  • Pyrimidine-6-carboxylic acid
  • Pyrimidone
  • Hydropyrimidine
  • Vinylogous amide
  • Heteroaromatic compound
  • Lactam
  • Urea
  • Carboxylic acid derivative
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Azacycle
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

  Health condition:

Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

  Organ and components:

Source:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Role

Industrial application:

  Pharmaceutical industry:

Indirect biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point345.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.82 mg/mL at 18 °CNot Available
LogP-0.83SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility4.51 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity33.27 m³·mol⁻¹ChemAxon
Polarizability12.46 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)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-EI-TOF (Non-derivatized)splash10-0udi-1982000000-b20f2ec9a2f1acc84ae1View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0zfr-2693000000-07bf11b5177412647d9bView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0udi-1972000000-c04fb7381d3ca07c9b0aView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-06ri-6900000000-4ba5fde1f8f62c4a2ba2View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0229-9850000000-8164142820eb5162e753View in MoNA
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
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-03di-0900000000-1b7abf52e4a01cb85541View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , negativesplash10-03di-0900000000-3dff3caa5c10aff8ce46View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-02ti-4900000000-6fd6312d81f94faaaf11View 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 AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,1H] 2D NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Amniotic Fluid
  • Blood
  • Feces
  • Saliva
  • Urine
Tissue Location
  • Liver
  • Pancreas
Pathways
NameSMPDB/PathwhizKEGG
Beta Ureidopropionase DeficiencyPw000187Pw000187 greyscalePw000187 simpleNot Available
Dihydropyrimidinase DeficiencyPw000189Pw000189 greyscalePw000189 simpleNot Available
MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy)Pw000190Pw000190 greyscalePw000190 simpleNot Available
Pyrimidine MetabolismPw000160Pw000160 greyscalePw000160 simpleMap00240
UMP Synthase Deficiency (Orotic Aciduria)Pw000188Pw000188 greyscalePw000188 simpleNot Available
Displaying all 5 entries
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
Amniotic FluidDetected and Quantified0.27 +/- 0.25 uMAdult (>18 years old)FemaleNormal details
BloodDetected and Quantified0.89 +/- 0.63 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified5.0 +/- 0.4 uMAdult (>18 years old)BothNormal details
FecesDetected but not Quantified Children (6 - 18 years old)Not SpecifiedNormal details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
UrineDetected and Quantified9.9 +/- 7.1 umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified0.63 +/- 0.21 umol/mmol creatinineAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified0-5 umol/mmol creatinineChildren (1 - 18 years old)Both
Normal
    • BC Children's Hos...
details
UrineDetected and Quantified0.23 +/- 0.13 umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified0.16 +/- 0.12 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified<4.33 umol/mmol creatinineChildren (1 - 18 years old)Both
Normal
    • BC Children's Hos...
details
UrineDetected and Quantified1.05 +/- 1.22 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified1.05 +/- 1.22 umol/mmol creatinineInfant (0-1 year old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.94 +/- 0.78 uMAdult (>18 years old)BothCanavan disease details
FecesDetected but not Quantified Adult (>18 years old)BothColorectal Cancer details
FecesDetected but not Quantified Children (6 - 18 years old)BothCrohns disease details
FecesDetected but not Quantified Children (6 - 18 years old)BothUlcerative colitis details
FecesDetected but not Quantified Children (6 - 18 years old)BothUlcerative colitis details
FecesDetected but not Quantified Children (6 - 18 years old)Not SpecifiedUnclassified IBD details
FecesDetected but not Quantified Children (6 - 18 years old)Not SpecifiedCrohns disease details
FecesDetected but not Quantified Children (6 - 18 years old)Not SpecifiedUlcerative colitis details
UrineDetected and Quantified5.5 (0.00-11.00) umol/mmol creatinineAdult (>18 years old)BothN-acetylglutamate synthetase deficiency details
UrineDetected and Quantified2.5 (0.00-5.00) umol/mmol creatinineChildren (1-13 years old)BothN-Acetylglutamate synthetase deficiency details
UrineDetected and Quantified3500.00 (1400.00-5600.00) umol/mmol creatinineChildren (1-13 years old)BothOrotic Aciduria hereditary details
UrineDetected and Quantified253.2 +/- 540.0 umol/mmol creatinineChildren (1-13 years old)Not SpecifiedOCT-deficient details
UrineDetected and Quantified6.11 +/- 5.48 umol/mmol creatinineAdult (>18 years old)BothCanavan disease details
Associated Disorders and Diseases
Disease References
Canavan disease
  1. Tavazzi B, Lazzarino G, Leone P, Amorini AM, Bellia F, Janson CG, Di Pietro V, Ceccarelli L, Donzelli S, Francis JS, Giardina B: Simultaneous high performance liquid chromatographic separation of purines, pyrimidines, N-acetylated amino acids, and dicarboxylic acids for the chemical diagnosis of inborn errors of metabolism. Clin Biochem. 2005 Nov;38(11):997-1008. Epub 2005 Sep 1. [PubMed:16139832 ]
N-acetylglutamate synthetase deficiency
    MetaGene
Orotic aciduria I
    MetaGene
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB012327
KNApSAcK IDC00019689
Chemspider ID942
KEGG Compound IDC00295
BioCyc IDOROTATE
BiGG ID34527
Wikipedia LinkOrotic acid
METLIN ID318
PubChem Compound967
PDB IDORO
ChEBI ID16742
References
Synthesis ReferenceMitchell, 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)
General References
  1. 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 ]
  2. Zieve L: Conditional deficiencies of ornithine or arginine. J Am Coll Nutr. 1986;5(2):167-76. [PubMed:3088083 ]
  3. Visek WJ: Ammonia: its effects on biological systems, metabolic hormones, and reproduction. J Dairy Sci. 1984 Mar;67(3):481-98. [PubMed:6371080 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. Visek WJ: Arginine and disease states. J Nutr. 1985 Apr;115(4):532-41. [PubMed:3884753 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. Brosnan ME, Brosnan JT: Orotic acid excretion and arginine metabolism. J Nutr. 2007 Jun;137(6 Suppl 2):1656S-1661S. [PubMed:17513443 ]

Enzymes

General function:
Involved in catalytic activity
Specific function:
Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
Gene Name:
DHODH
Uniprot ID:
Q02127
Molecular weight:
42866.93
Reactions
L-Dihydroorotic acid + a quinone → Orotic acid + a quinoldetails
L-Dihydroorotic acid + Quinone → Orotic acid + Hydroquinonedetails
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
UMPS
Uniprot ID:
P11172
Molecular weight:
52221.075
Reactions
Orotidylic acid + Pyrophosphate → Orotic acid + Phosphoribosyl pyrophosphatedetails