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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-02-09 00:07:51 UTC
HMDB IDHMDB00076
Secondary Accession NumbersNone
Metabolite Identification
Common NameDihydrouracil
DescriptionDihydrouracil 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. Patients with dihydropyrimidinase deficiency (DPYS; also called 5, 6-dihydropyrimidine amidohydrolase, or DHP; EC 3.5.2.2) exhibit highly increased concentrations of 5, 6-dihydrouracil in urine. The direct measurement of the activity of DHP in patients had been hampered by the fact that the enzyme is expressed almost exclusively in liver tissue. Various neurological abnormalities have been described in this group of patients. (OMIM 222748 ).
Structure
Thumb
Synonyms
  1. 5,6-Dihydro-2,4(1H,3H)-pyrimidinedione
  2. 5,6-Dihydro-2,4-dihydroxypyrimidine
  3. 5,6-Dihydrouracil
  4. Dihydro-2,4(1H,3H)-pyrimidinedione
  5. Dihydro-pyrimidine-2,4-dione
  6. Dihydrouracil
  7. Dihydrouracile
  8. Hydrouracil
Chemical FormulaC4H6N2O2
Average Molecular Weight114.1026
Monoisotopic Molecular Weight114.042927446
IUPAC Name1,3-diazinane-2,4-dione
Traditional IUPAC Name3,4-dihydrouracil
CAS Registry Number504-07-4
SMILES
O=C1CCNC(=O)N1
InChI Identifier
InChI=1S/C4H6N2O2/c7-3-1-2-5-4(8)6-3/h1-2H2,(H2,5,6,7,8)
InChI KeyOIVLITBTBDPEFK-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
Biofunction
  • Component of Pantothenate and CoA biosynthesis
  • Component of Pyrimidine metabolism
  • Component of beta-Alanine metabolism
ApplicationNot Available
Cellular locations
  • Cytoplasm
  • Nucleus
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point279 - 281 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
water solubility25.9 g/LALOGPS
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 area58.2ChemAxon
rotatable bond count0ChemAxon
refractivity25.75ChemAxon
polarizability10.13ChemAxon
Spectra
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
  • Nucleus
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Fibroblasts
  • Kidney
  • Liver
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Beta-Alanine MetabolismSMP00007map00410
Pyrimidine MetabolismSMP00046map00240
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.31 (0.02-1.63) uMAdult (>18 years old)FemaleNormal details
BloodDetected and Quantified0.31 (0.02-1.63) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.32 ( 0.10-0.74) uMAdult (>18 years old)MaleNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified2.1 +/- 1.0 uMAdult (>18 years old)Not SpecifiedNormal details
UrineDetected and Quantified0.79 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified3.8 (2.1-8.3) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified2.4 +/- 4.7 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified3.0 +/- 2.7 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified12.2 +/- 6.2 umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
Cerebrospinal Fluid (CSF)Detected and Quantified81.5 (46.0-117.0) uMAdult (>18 years old)BothDihydropyrimidine dehydrogenase (DPD) deficiency details
UrineDetected and Quantified2.4 +/- 1.67 umol/mmol creatinineAdult (>18 years old)BothHypertension details
UrineDetected and Quantified627.0 umol/mmol creatinineInfant (0-1 year old)BothDihydropyrimidine dehydrogenase (DPD) deficiency details
UrineDetected and Quantified2.4 +/- 2.00 umol/mmol creatinineAdult (>18 years old)BothCerebral infarction details
UrineDetected and Quantified2.8 +/- 1.9 umol/mmol creatinineAdult (>18 years old)BothMalignancy details
UrineDetected and Quantified2.7 +/- 1.9 umol/mmol creatinineAdult (>18 years old)BothLiver dysfunction details
UrineDetected and Quantified2.5 +/- 2.00 umol/mmol creatinineAdult (>18 years old)BothNephropathy details
Associated Disorders and Diseases
Disease References
Dihydropyrimidine dehydrogenase deficiency
  1. 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
  2. Van Kuilenburg AB, Stroomer AE, Van Lenthe H, Abeling NG, Van Gennip AH: New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for beta-aminoisobutyric acid? Biochem J. 2004 Apr 1;379(Pt 1):119-24. Pubmed: 14705962
Hypertension
  1. Hayashi K, Kidouchi K, Sumi S, Mizokami M, Orito E, Kumada K, Ueda R, Wada Y: Possible prediction of adverse reactions to pyrimidine chemotherapy from urinary pyrimidine levels and a case of asymptomatic adult dihydropyrimidinuria. Clin Cancer Res. 1996 Dec;2(12):1937-41. Pubmed: 9816152
Associated OMIM IDs
  • 274270 (Dihydropyrimidine dehydrogenase deficiency)
  • 145500 (Hypertension)
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB021890
KNApSAcK IDNot Available
Chemspider ID629
KEGG Compound IDC00429
BioCyc IDDI-H-URACIL
BiGG ID34956
Wikipedia LinkNot Available
NuGOwiki LinkHMDB00076
Metagene LinkHMDB00076
METLIN ID285
PubChem Compound649
PDB IDDUC
ChEBI ID15901
References
Synthesis ReferenceBhat, 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)
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. Van Kuilenburg AB, Stroomer AE, Van Lenthe H, Abeling NG, Van Gennip AH: New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for beta-aminoisobutyric acid? Biochem J. 2004 Apr 1;379(Pt 1):119-24. Pubmed: 14705962
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. Tan BR, McLeod HL: Pharmacogenetic influences on treatment response and toxicity in colorectal cancer. Semin Oncol. 2005 Feb;32(1):113-9. Pubmed: 15726513
  12. 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
  13. 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
  14. 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

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
Dihydrouracil + Water → Ureidopropionic 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
Dihydrouracil + NADP → Uracil + NADPHdetails
Dihydrouracil + NADP → Uracil + NADPH + Hydrogen Iondetails