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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2019-07-23 05:43:53 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 into 5,6-dihydrothymine then dihydropyrimidinase hydrolyzes 5,6-dihydrothymine into N-carbamyl-beta-alanine. Finally, beta-ureidopropionase catalyzes the conversion of N-carbamyl-beta-alanine to beta-alanine. When present at abnormally high levels, dihydrothymine can be toxic, although the mechanism of toxicity is not clear. In particular, 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. Dihydropyrimidinase deficiency is a disorder that can cause neurological and gastrointestinal problems in some affected individuals. The most common neurological abnormalities that occur are intellectual disability, seizures, weak muscle tone (hypotonia), abnormally small head size (microcephaly), and autistic behaviours that affect communication and social interaction. Gastrointestinal problems that occur in dihydropyrimidinase deficiency include backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and recurrent episodes of vomiting.
Structure
Data?1563860633
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-MethyldihydrouracilHMDB
5,6-Dihydrothymine, (S)-isomerHMDB
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
Description belongs to the class of organic compounds known as hydropyrimidines. Hydropyrimidines are compounds containing a hydrogenated pyrimidine ring (i.e. containing less than the maximum number of double bonds.).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentHydropyrimidines
Alternative Parents
Substituents
  • 5,6-dihydropyrimidine
  • Hydropyrimidine
  • Azacycle
  • 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
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Role

Biological role:

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 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity30.32 m³·mol⁻¹ChemAxon
Polarizability12.03 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-000i-5900000000-0b84b9786838d29e07abJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0zmi-8980000000-d75d30c6e5fdb4643aa5JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-000i-5900000000-0b84b9786838d29e07abJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0zmi-8980000000-d75d30c6e5fdb4643aa5JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004i-9300000000-05ab95b9effabc03847dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-004i-8900000000-db662635cbae4d48204bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0006-9000000000-c3960ffe99d74c617000JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0006-9000000000-9a6c2715f931ff084157JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0900000000-b0b2721bf2e4a74bbba2JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4l-9100000000-b89dfebf5db699f3651cJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052f-9000000000-97f152f0bbe6fb600c5cJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-3900000000-98c26fdc1559c4c1afc2JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-9000000000-320f4c88705757a63b75JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-76fbb95e0354defdb94eJSpectraViewer | MoNA
MSMass Spectrum (Electron Ionization)splash10-004l-9200000000-873ae62dcdf602237ec1JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Saliva
  • Urine
Tissue Locations
  • Prostate
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
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
    FecesDetected but not Quantified Adult (>18 years old)Both
    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
    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
    BiospecimenStatusValueAgeSexConditionReferenceDetails
    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
    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 ]
    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 ]
    Eosinophilic esophagitis
    1. (). Mordechai, Hien, and David S. Wishart. .
    Associated OMIM IDs
    • 222748 (Dihydropyrimidinase deficiency)
    • 613161 (Beta-ureidopropionase deficiency)
    • 610247 (Eosinophilic esophagitis)
    DrugBank IDNot Available
    Phenol Explorer Compound IDNot Available
    FoodDB IDFDB021892
    KNApSAcK IDNot Available
    Chemspider ID84456
    KEGG Compound IDC00906
    BioCyc IDNot Available
    BiGG ID36347
    Wikipedia LinkDihydrothymine
    METLIN ID5135
    PubChem Compound93556
    PDB IDNot Available
    ChEBI ID27468
    Food Biomarker OntologyNot Available
    VMH IDNot Available
    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. 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 ]
    2. 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 ]
    3. 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 ]
    4. 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 ]
    5. 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 ]
    6. 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 ]
    7. 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 ]
    8. 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 ]
    9. 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 ]

    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