Record Information
Version2.0
Creation Date2012-05-31 09:56:44 -0600
Update Date2015-09-13 12:56:05 -0600
Secondary Accession Numbers
  • ECMDB00076
Identification
Name:Dihydrouracil
DescriptionDihydrohuracil is an intermediate breakdown product of uracil. Dihydropyrimidine dehydrogenase catalyzes the reduction of uracil to 5, 6-dihydrouracil then dihydropyrimidinase hydrolyzes 5, 6-dihydrouracil to N-carbamyl-b-alanine. Finally, beta-ureidopropionase catalyzes the conversion of N-carbamyl-b-alanine to beta-alanine.
Structure
Thumb
Synonyms:
  • 5,6-Dihydro-2,4(1H,3H)-pyrimidinedione
  • 5,6-Dihydro-2,4-dihydroxypyrimidine
  • 5,6-Dihydrouracil
  • DI-H-uracil
  • Dihydro-2,4(1H,3H)-pyrimidinedione
  • Dihydro-pyrimidine-2,4-dione
  • Dihydrouracil
  • Dihydrouracile
  • Hydrouracil
Chemical Formula:C4H6N2O2
Weight:Average: 114.1026
Monoisotopic: 114.042927446
InChI Key:OIVLITBTBDPEFK-UHFFFAOYSA-N
InChI:InChI=1S/C4H6N2O2/c7-3-1-2-5-4(8)6-3/h1-2H2,(H2,5,6,7,8)
CAS number:504-07-4
IUPAC Name:1,3-diazinane-2,4-dione
Traditional IUPAC Name:dihydrouracil
SMILES:O=C1CCNC(=O)N1
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyrimidones. Pyrimidones are compounds that contain a pyrimidine ring, which bears a ketone. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentPyrimidones
Alternative Parents
Substituents
  • N-acyl urea
  • Pyrimidone
  • Ureide
  • 1,3-diazinane
  • Dicarboximide
  • Urea
  • Carbonic acid derivative
  • Azacycle
  • Carboxylic acid derivative
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Physical Properties
State:Solid
Charge:0
Melting point:279-281 °C
Experimental Properties:
PropertyValueSource
Predicted Properties
PropertyValueSource
Water Solubility25.9 g/LALOGPS
logP-1.3ALOGPS
logP-1.2ChemAxon
logS-0.64ALOGPS
pKa (Strongest Acidic)11.73ChemAxon
pKa (Strongest Basic)-7.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.2 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity25.75 m³·mol⁻¹ChemAxon
Polarizability10.13 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Biological Properties
Cellular Locations:Cytoplasm
Reactions:
SMPDB Pathways:
Pantothenate and CoA biosynthesisPW000828 ThumbThumb?image type=greyscaleThumb?image type=simple
Pyrimidine metabolismPW000942 ThumbThumb?image type=greyscaleThumb?image type=simple
beta-Alanine metabolismPW000896 ThumbThumb?image type=greyscaleThumb?image type=simple
KEGG Pathways:
EcoCyc Pathways:Not Available
Concentrations
Not Available
Spectra
Spectra:
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)splash10-00di-9700000000-4adeeb2f4f5a1111afb7View in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-00di-5900000000-8af1b81502646fa5b417View in MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0fdo-9750000000-d2aaeeba1cf962175f84View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00di-9700000000-4adeeb2f4f5a1111afb7View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00di-5900000000-8af1b81502646fa5b417View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0fdo-9750000000-d2aaeeba1cf962175f84View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0f6w-2940000000-3430a0e2d1819021af1dView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00di-3900000000-79f2d90a419b7469cb61View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004l-9100000000-55536f0571922b6c69feView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableView in JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-03k9-9800000000-da772cea603c785c1df4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0a4i-9100000000-94a5f543e8c6be7b3204View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0btc-9200000000-e9bf2ae82714a2a3a737View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-014i-5900000000-0fe83e63f6e5d1347894View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , negativesplash10-03xr-6900000000-08aca1bc7f27b0e7cb08View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-5900000000-53ea361c86b4f9fa284bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-9300000000-a8599c09cd21e2f84329View in MoNA
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-01b9-9500000000-03c8b6a5b2dc3625d5d3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0ab9-9000000000-331f648f78f506788b99View in MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-052f-9000000000-824aa91d3f2de539f0bdView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-2900000000-ad7f91d5265e53403dd6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0603-9200000000-4b30a83fb454e5bbffb8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-ce54e3c860a95b0af401View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-9800000000-d705e188f6700a76ef72View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-9000000000-a26409d69a4259731004View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-f00c4df547660023bee4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0900000000-b8f2cf36966bbbbb3285View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-9500000000-44775319047d2eddad49View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052f-9000000000-3cb7005ca8389854848eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03dl-7900000000-9d78d5698ad7865d1789View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-9000000000-997cffdd9ad85c899225View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-a88e812ae86e53f6c2d6View in MoNA
MSMass Spectrum (Electron Ionization)splash10-03fu-9400000000-5b9edda3479e7d0a0d28View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
References
References:
  • Assmann B, Hoffmann GF, Wagner L, Brautigam C, Seyberth HW, Duran M, Van Kuilenburg AB, Wevers R, Van Gennip AH: Dihydropyrimidinase deficiency and congenital microvillous atrophy: coincidence or genetic relation? J Inherit Metab Dis. 1997 Sep;20(5):681-8. Pubmed: 9323563
  • Garcia AA, Blessing JA, Lenz HJ, Darcy KM, Mannel RS, Miller DS, Husseinzadeh N: Phase II clinical trial of capecitabine in ovarian carcinoma recurrent 6-12 months after completion of primary chemotherapy, with exploratory TS, DPD, and TP correlates: a Gynecologic Oncology Group study. Gynecol Oncol. 2005 Mar;96(3):810-7. Pubmed: 15721430
  • Grem JL: Intratumoral molecular or genetic markers as predictors of clinical outcome with chemotherapy in colorectal cancer. Semin Oncol. 2005 Feb;32(1):120-7. Pubmed: 15726514
  • Hofmann U, Schwab M, Seefried S, Marx C, Zanger UM, Eichelbaum M, Murdter TE: Sensitive method for the quantification of urinary pyrimidine metabolites in healthy adults by gas chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 5;791(1-2):371-80. Pubmed: 12798197
  • Jiang H, Jiang J, Hu P, Hu Y: Measurement of endogenous uracil and dihydrouracil in plasma and urine of normal subjects by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Mar 25;769(1):169-76. Pubmed: 11936689
  • 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
  • Megyeri A, Bacso Z, Shields A, Eliason JF: Development of a stereological method to measure levels of fluoropyrimidine metabolizing enzymes in tumor sections using laser scanning cytometry. Cytometry A. 2005 Apr;64(2):62-71. Pubmed: 15729713
  • Nakamura A, Kikuchi K, Ohishi T, Masuike T: [Assay method for uracil, dihydrouracil, 5-fluorouracil and 5-fluoro-5, 6-dihydrouracil by high-performance liquid chromatography] Gan To Kagaku Ryoho. 2004 Mar;31(3):381-6. Pubmed: 15045945
  • Schneider S, Uchida K, Brabender J, Baldus SE, Yochim J, Danenberg KD, Salonga D, Chen P, Tsao-Wei D, Groshen S, Hoelscher AH, Schneider PM, Danenberg PV: Downregulation of TS, DPD, ERCC1, GST-Pi, EGFR, and HER2 gene expression after neoadjuvant three-modality treatment in patients with esophageal cancer. J Am Coll Surg. 2005 Mar;200(3):336-44. Pubmed: 15737843
  • Shen GP, Galick H, Inoue M, Wallace SS: Decline of nuclear and mitochondrial oxidative base excision repair activity in late passage human diploid fibroblasts. DNA Repair (Amst). 2003 Jun 11;2(6):673-93. Pubmed: 12767347
  • 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. Pubmed: 19212411
  • Sumi S, Kidouchi K, Ohba S, Wada Y: Automated screening system for purine and pyrimidine metabolism disorders using high-performance liquid chromatography. J Chromatogr B Biomed Appl. 1995 Oct 20;672(2):233-9. Pubmed: 8581129
  • Tan BR, McLeod HL: Pharmacogenetic influences on treatment response and toxicity in colorectal cancer. Semin Oncol. 2005 Feb;32(1):113-9. Pubmed: 15726513
  • 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, A. B., Stroomer, A. E., Van Lenthe, H., Abeling, N. G., Van Gennip, A. H. (2004). "New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for beta-aminoisobutyric acid?" Biochem J 379:119-124. Pubmed: 14705962
  • van Lenthe H, van Kuilenburg AB, Ito T, Bootsma AH, van Cruchten A, Wada Y, van Gennip AH: Defects in pyrimidine degradation identified by HPLC-electrospray tandem mass spectrometry of urine specimens or urine-soaked filter paper strips. Clin Chem. 2000 Dec;46(12):1916-22. Pubmed: 11106323
  • 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
Synthesis Reference:Bhat, K. S.; Rao, A. S. Synthesis of uracil, 6-methyluracil and some dihydrouracils. Organic Preparations and Procedures International (1983), 15(5), 303-13.
Material Safety Data Sheet (MSDS)Download (PDF)
External Links:
ResourceLink
CHEBI ID15901
HMDB IDHMDB00076
Pubchem Compound ID649
Kegg IDC00429
ChemSpider ID629
Wikipedia IDDihydrouracil
BioCyc IDDI-H-URACIL
EcoCyc IDDI-H-URACIL
Ligand ExpoDUC

Enzymes

General function:
Involved in hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides
Specific function:
Catalyzes the stereospecific hydrolysis of the cyclic amide bond of D-hydantoin derivatives with an aromatic side chains at the 5'-position. Has no activity on dihydropyrimidines. The physiological function is unknown
Gene Name:
hyuA
Uniprot ID:
Q46806
Molecular weight:
51025
General function:
Involved in iron-sulfur cluster binding
Specific function:
Specific function unknown
Gene Name:
yeiA
Uniprot ID:
P25889
Molecular weight:
45069
Reactions
5,6-dihydrouracil + NAD(+) = uracil + NADH.
5,6-dihydrothymine + NAD(+) = thymine + NADH.
General function:
Involved in oxidoreductase activity
Specific function:
Specific function unknown
Gene Name:
yeiT
Uniprot ID:
P76440
Molecular weight:
44329
Reactions
5,6-dihydrouracil + NAD(+) = uracil + NADH.
5,6-dihydrothymine + NAD(+) = thymine + NADH.