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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2017-08-16 03:10:46 UTC
HMDB IDHMDB0000079
Secondary Accession Numbers
  • HMDB00079
Metabolite Identification
Common NameDihydrothymine
DescriptionDihydrothymine is an intermediate breakdown product of thymine. Dihydropyrimidine dehydrogenase catalyzes the reduction of thymine to 5, 6-dihydrothymine then dihydropyrimidinase hydrolyzes 5, 6-dihydrothymine to N-carbamyl-b-alanine. Finally, beta-ureidopropionase catalyzes the conversion of N-carbamyl-b-alanine to beta-alanine. Patients with dihydropyrimidinase deficiency exhibit highly increased concentrations of 5, 6-dihydrouracil and 5, 6-dihydrothymine and moderately increased concentrations of uracil and thymine can be detected in urine.
Structure
Thumb
Synonyms
ValueSource
5,6-dihydro-5-MethyluracilChEBI
5-Methyl-5,6-dihydrouracilChEBI
5,6-DihydrothymineHMDB
5-Methyl-hydrouracilHMDB
5-Methyldihydropyrimidine-2,4(1H,3H)-dioneHMDB
dihydro-5-Methyl-2,4(1H,3H)-pyrimidinedioneHMDB
5-MethyldihydrouracilMeSH
5,6-Dihydrothymine, (S)-isomerMeSH
Chemical FormulaC5H8N2O2
Average Molecular Weight128.1292
Monoisotopic Molecular Weight128.05857751
IUPAC Name5-methyl-1,3-diazinane-2,4-dione
Traditional Namedihydrothymine
CAS Registry Number696-04-8
SMILES
CC1CNC(=O)NC1=O
InChI Identifier
InChI=1S/C5H8N2O2/c1-3-2-6-5(9)7-4(3)8/h3H,2H2,1H3,(H2,6,7,8,9)
InChI KeyNBAKTGXDIBVZOO-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as ureides. These are compounds containing an ureide group with the general structure R1-CO-NH-CO-N(R)2R3, formally derived by the acylation of urea. They can be subdivided in N-acyl or N,N'-diacyl ureas.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassOrganic carbonic acids and derivatives
Direct ParentUreides
Alternative Parents
Substituents
  • Ureide
  • 5,6-dihydropyrimidine
  • Hydropyrimidine
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Cytoplasm
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility18.7 mg/mLALOGPS
logP-0.8ALOGPS
logP-0.67ChemAxon
logS-0.84ALOGPS
pKa (Strongest Acidic)11.7ChemAxon
pKa (Strongest Basic)-7.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.2 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity30.32 m3·mol-1ChemAxon
Polarizability12.03 Å3ChemAxon
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-MS (1 TMS)splash10-000i-5900000000-0b84b9786838d29e07abView in MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0zmi-8980000000-d75d30c6e5fdb4643aa5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-004i-8900000000-db662635cbae4d48204bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0006-9000000000-c3960ffe99d74c617000View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0006-9000000000-9a6c2715f931ff084157View in MoNA
MSMass Spectrum (Electron Ionization)splash10-004l-9200000000-873ae62dcdf602237ec1View 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
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue Location
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Beta Ureidopropionase DeficiencySMP00172Not Available
Dihydropyrimidinase DeficiencySMP00178Not Available
MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy)SMP00202Not Available
Pyrimidine MetabolismSMP00046map00240
UMP Synthase Deiciency (Orotic Aciduria)SMP00219Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot Available
Normal
    details
    Cerebrospinal Fluid (CSF)Detected and Quantified1.1 +/- 0.3 uMAdult (>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 Quantified0.4 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified5.00 (0.00-10.00) umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified0-3 umol/mmol creatinineChildren (1 - 18 years old)Both
    Normal
      • BC Children's Hos...
    details
    UrineDetected and Quantified2.4 (1.3-4.4) umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified8.736 +/- 1.827 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
    Normal
      • Mordechai, Hien, ...
    details
    UrineDetected and Quantified0.40 (0.17-0.64) umol/mmol creatinineAdult (>18 years old)MaleNormal details
    UrineDetected and Quantified0.57 (0.21-0.94) umol/mmol creatinineAdult (>18 years old)FemaleNormal details
    Abnormal Concentrations
    BiofluidStatusValueAgeSexConditionReferenceDetails
    Cerebrospinal Fluid (CSF)Detected and Quantified0.0 - 24.0 uMNot SpecifiedBothDihydropyrimidinase deficiency details
    Cerebrospinal Fluid (CSF)Detected and Quantified4.0 - 5.2 uMAdult (>18 years old)Not SpecifiedBeta-ureidopropionase deficiency details
    UrineDetected and Quantified11.664 +/- 5.285 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
    Eosinophilic esophagitis
      • Mordechai, Hien, ...
    details
    Associated Disorders and Diseases
    Disease References
    Beta-ureidopropionase deficiency
    1. van Kuilenburg AB, Meinsma R, Beke E, Assmann B, Ribes A, Lorente I, Busch R, Mayatepek E, Abeling NG, van Cruchten A, Stroomer AE, van Lenthe H, Zoetekouw L, Kulik W, Hoffmann GF, Voit T, Wevers RA, Rutsch F, van Gennip AH: beta-Ureidopropionase deficiency: an inborn error of pyrimidine degradation associated with neurological abnormalities. Hum Mol Genet. 2004 Nov 15;13(22):2793-801. Epub 2004 Sep 22. [PubMed:15385443 ]
    Dihydropyrimidinase deficiency
    1. van Kuilenburg AB, Meijer J, Dobritzsch D, Meinsma R, Duran M, Lohkamp B, Zoetekouw L, Abeling NG, van Tinteren HL, Bosch AM: Clinical, biochemical and genetic findings in two siblings with a dihydropyrimidinase deficiency. Mol Genet Metab. 2007 Jun;91(2):157-64. Epub 2007 Mar 26. [PubMed:17383919 ]
    Associated OMIM IDs
    • 222748 (Dihydropyrimidinase deficiency)
    • 613161 (Beta-ureidopropionase deficiency)
    DrugBank IDNot Available
    DrugBank Metabolite IDNot Available
    Phenol Explorer Compound IDNot Available
    Phenol Explorer Metabolite IDNot Available
    FoodDB IDFDB021892
    KNApSAcK IDNot Available
    Chemspider ID84456
    KEGG Compound IDC00906
    BioCyc IDDIHYDRO-THYMINE
    BiGG ID36347
    Wikipedia LinkNot Available
    NuGOwiki LinkHMDB0000079
    METLIN ID5135
    PubChem Compound93556
    PDB IDNot Available
    ChEBI ID27468
    References
    Synthesis ReferenceYamane, Tetsuo; Wyluda, Benjamin J.; Shulman, Robert G. Dihydrothymine from ultraviolet-irradiated DNA. Proceedings of the National Academy of Sciences of the United States of America (1967), 58(2), 439-42.
    Material Safety Data Sheet (MSDS)Download (PDF)
    General References
    1. 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. doi: 10.1038/nature07762. [PubMed:19212411 ]
    2. 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 ]
    3. 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 ]
    4. 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 ]
    5. Rosenbaum K, Jahnke K, Curti B, Hagen WR, Schnackerz KD, Vanoni MA: Porcine recombinant dihydropyrimidine dehydrogenase: comparison of the spectroscopic and catalytic properties of the wild-type and C671A mutant enzymes. Biochemistry. 1998 Dec 15;37(50):17598-609. [PubMed:9860876 ]
    6. Sumi S, Kidouchi K, Kondou M, Hayashi K, Dobashi K, Kouwaki M, Togari H, Wada Y: Possible prediction of adverse reactions to fluorouracil by the measurement of urinary dihydrothymine and thymine. Int J Mol Med. 1998 Oct;2(4):477-82. [PubMed:9857238 ]
    7. Van Kuilenburg AB, Van Lenthe H, Van Gennip AH: Identification and tissue-specific expression of a NADH-dependent activity of dihydropyrimidine dehydrogenase in man. Anticancer Res. 1996 Jan-Feb;16(1):389-94. [PubMed:8615641 ]
    8. Kobayashi K, Sumi S, Kidouchi K, Mizuno I, Mohri N, Fukui T, Akamo Y, Takeyama H, Manabe T: [A case of gastric cancer with decreased dihydropyrimidine dehydrogenase activity]. Gan To Kagaku Ryoho. 1998 Jul;25(8):1217-9. [PubMed:9679586 ]
    9. Sumi S, Imaeda M, Kidouchi K, Ohba S, Hamajima N, Kodama K, Togari H, Wada Y: Population and family studies of dihydropyrimidinuria: prevalence, inheritance mode, and risk of fluorouracil toxicity. Am J Med Genet. 1998 Jul 24;78(4):336-40. [PubMed:9714435 ]

    Enzymes

    General function:
    Involved in hydrolase activity
    Specific function:
    Catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Can catalyze the ring opening of 5,6-dihydrouracil to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-amino isobutyrate.
    Gene Name:
    DPYS
    Uniprot ID:
    Q14117
    Molecular weight:
    56629.36
    Reactions
    Dihydrothymine + Water → Ureidoisobutyric aciddetails
    General function:
    Involved in electron carrier activity
    Specific function:
    Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil.
    Gene Name:
    DPYD
    Uniprot ID:
    Q12882
    Molecular weight:
    111400.32
    Reactions
    Dihydrothymine + NADP → Thymine + NADPH + Hydrogen Iondetails