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
Description:Dihydrohuracil 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
DescriptionThis compound belongs to the class of chemical entities known as pyrimidones. These 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.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassDiazines
Direct ParentPyrimidones
Alternative Parents
Substituents
  • Pyrimidone
  • Ureide
  • 1,3-diazinane
  • Dicarboximide
  • Urea
  • 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 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity25.75 m3·mol-1ChemAxon
Polarizability10.13 Å3ChemAxon
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 Pw000828Pw000828 greyscalePw000828 simple
Pyrimidine metabolismPW000942 Pw000942Pw000942 greyscalePw000942 simple
beta-Alanine metabolismPW000896 Pw000896Pw000896 greyscalePw000896 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-MSsplash10-004l-9100000000-55536f0571922b6c69feView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOFsplash10-00di-9700000000-4adeeb2f4f5a1111afb7View in MoNA
GC-MSGC-MS Spectrum - GC-MSsplash10-00di-5900000000-8af1b81502646fa5b417View in MoNA
GC-MSGC-MS Spectrum - GC-MSsplash10-0fdo-9750000000-d2aaeeba1cf962175f84View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOFsplash10-0f6w-2940000000-3430a0e2d1819021af1dView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOFsplash10-00di-3900000000-79f2d90a419b7469cb61View in MoNA
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
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
MSMass Spectrum (Electron Ionization)splash10-03fu-9400000000-5b9edda3479e7d0a0d28View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
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.