Dihydrothymine (T3D4332)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationXML
Record Information
Version2.0
Creation Date2014-08-29 06:28:37 UTC
Update Date2018-03-21 17:46:23 UTC
Accession NumberT3D4332
Identification
Common NameDihydrothymine
ClassSmall Molecule
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.
Compound Type
  • Animal Toxin
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
5,6-Dihydro-5-methyluracil
5,6-Dihydrothymine
5-Methyl-5,6-dihydrouracil
5-Methyl-Hydrouracil
5-Methyldihydropyrimidine-2,4(1H,3H)-dione
Dihydro-5-methyl-2,4(1H,3H)-Pyrimidinedione
Chemical FormulaC5H8N2O2
Average Molecular Mass128.129 g/mol
Monoisotopic Mass128.059 g/mol
CAS Registry Number696-04-8
IUPAC Name5-methyl-1,3-diazinane-2,4-dione
Traditional Namedihydrothymine
SMILESCC1CN=C(O)N=C1O
InChI IdentifierInChI=1/C5H8N2O2/c1-3-2-6-5(9)7-4(3)8/h3H,2H2,1H3,(H2,6,7,8,9)
InChI KeyInChIKey=NBAKTGXDIBVZOO-UHFFFAOYNA-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
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Pyrimidine MetabolismSMP00046 map00240
Dihydropyrimidinase DeficiencySMP00178 Not Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot 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
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-000i-5900000000-0b84b9786838d29e07ab2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0zmi-8980000000-d75d30c6e5fdb4643aa52014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-000i-5900000000-0b84b9786838d29e07ab2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0zmi-8980000000-d75d30c6e5fdb4643aa52017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004i-9300000000-05ab95b9effabc03847d2017-09-01View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-004i-8900000000-db662635cbae4d48204b2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0006-9000000000-c3960ffe99d74c6170002012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0006-9000000000-9a6c2715f931ff0841572012-07-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0900000000-b0b2721bf2e4a74bbba22017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4l-9100000000-b89dfebf5db699f3651c2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052f-9000000000-97f152f0bbe6fb600c5c2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-3900000000-98c26fdc1559c4c1afc22017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-9000000000-320f4c88705757a63b752017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-76fbb95e0354defdb94e2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0900000000-7c6c3743140aa087d39c2021-10-21View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-4900000000-70eb9f3b90f3b230f5932021-10-21View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4l-9000000000-e84dd91c5dd8c38010f72021-10-21View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-3900000000-b1b06bf61dca14c340152021-10-21View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-9200000000-a8831b6e3dbc59c569632021-10-21View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-90726b17dc36e29c52992021-10-21View Spectrum
MSMass Spectrum (Electron Ionization)splash10-004l-9200000000-873ae62dcdf602237ec12014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, DMSO-d6, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 15.09 MHz, DMSO-d6, experimental)Not Available2014-09-23View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityDihydropyrimidine 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. Accumulation of dihydrothymine in the body has been shown to be toxic.
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThis is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB00079
PubChem Compound ID93556
ChEMBL IDNot Available
ChemSpider ID84456
KEGG IDC00906
UniProt IDNot Available
OMIM ID
ChEBI ID27468
BioCyc IDDIHYDRO-THYMINE
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot 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.
MSDSLink
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. [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. [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. [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. [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. [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. [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. [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. [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. [19212411 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available