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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-02-09 00:07:52 UTC
HMDB IDHMDB00079
Secondary Accession NumbersNone
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
  1. 5,6-Dihydro-5-methyluracil
  2. 5,6-Dihydrothymine
  3. 5-Methyl-5,6-dihydrouracil
  4. 5-Methyl-Hydrouracil
  5. 5-Methyldihydropyrimidine-2,4(1H,3H)-dione
  6. Dihydro-5-methyl-2,4(1H,3H)-Pyrimidinedione
  7. Dihydrothymine
Chemical FormulaC5H8N2O2
Average Molecular Weight128.1292
Monoisotopic Molecular Weight128.05857751
IUPAC Name5-methyl-1,3-diazinane-2,4-dione
Traditional IUPAC 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
KingdomOrganic Compounds
Super ClassAliphatic Heteromonocyclic Compounds
ClassDiazines
Sub ClassPyrimidines and Pyrimidine Derivatives
Other Descriptors
  • Aliphatic Heteromonocyclic Compounds
  • Pyrimidines and Pyrimidine Derivatives
  • Ureides
  • a base derivative(Cyc)
  • a pyrimidine-related compound(Cyc)
  • pyrimidone(ChEBI)
Substituents
  • Carboxamide Group
  • Carboxylic Acid Imide, N Unsubstituted
  • Urea
Direct ParentPyrimidones
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 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 area58.2ChemAxon
rotatable bond count0ChemAxon
refractivity30.32ChemAxon
polarizability12.03ChemAxon
Spectra
SpectraGC-MSMS/MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Pyrimidine MetabolismSMP00046map00240
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot Available
Normal
  • Not Applicable
details
Cerebrospinal Fluid (CSF)Detected and Quantified1.1 +/- 0.3 uMAdult (>18 years old)Not SpecifiedNormal 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 Quantified2.4 (1.3-4.4) umol/mmol creatinineAdult (>18 years old)Both
Normal
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
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 LinkHMDB00079
Metagene LinkHMDB00079
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. 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):477-482. 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