Human Metabolome Database Version 3.5

Showing metabocard for Dihydrouracil (HMDB00076)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-02-08 17:07:51 -0700
HMDB ID HMDB00076
Secondary Accession Numbers None
Metabolite Identification
Common Name Dihydrouracil
Description Dihydrouracil 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 Link_out).
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
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 Formula C4H6N2O2
Average Molecular Weight 114.1026
Monoisotopic Molecular Weight 114.042927446
IUPAC Name 1,3-diazinane-2,4-dione
Traditional IUPAC Name 3,4-dihydrouracil
CAS Registry Number 504-07-4
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 Key OIVLITBTBDPEFK-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Aliphatic Heteromonocyclic Compounds
Class Diazines
Sub Class Pyrimidines 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 Parent Pyrimidones
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Pantothenate and CoA biosynthesis
  • Component of Pyrimidine metabolism
  • Component of beta-Alanine metabolism
Application Not Available
Cellular locations
  • Cytoplasm
  • Nucleus
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 279 - 281 °C Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 25.9 g/L ALOGPS
LogP -1.28 ALOGPS
LogP -1.2 ChemAxon
LogS -0.64 ALOGPS
pKa (strongest acidic) 11.73 ChemAxon
pKa (strongest basic) -7.6 ChemAxon
Hydrogen Acceptor Count 2 ChemAxon
Hydrogen Donor Count 2 ChemAxon
Polar Surface Area 58.2 A2 ChemAxon
Rotatable Bond Count 0 ChemAxon
Refractivity 25.75 ChemAxon
Polarizability 10.13 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge 0 ChemAxon
Spectra
1H NMR Spectrum
MS/MS Spectrum Quattro_QQQ 10
MS/MS Spectrum Quattro_QQQ 25
MS/MS Spectrum Quattro_QQQ 40
MS/MS Spectrum GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)
MS/MS Spectrum LC-ESI-QTOF (UPLC Q-Tof Premier, Waters)
MS/MS Spectrum GC-MS
MS/MS Spectrum GC-MS
[1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Nucleus
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Fibroblasts
  • Kidney
  • Liver
  • Prostate
Pathways
Name SMPDB Link KEGG Link
Pyrimidine Metabolism SMP00046 map00240 Link_out
Beta-Alanine Metabolism SMP00007 map00410 Link_out
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
0.31 (0.02-1.63) uM Adult (>18 years old) Female Normal
Blood Detected and Quantified
0.31 (0.02-1.63) uM Adult (>18 years old) Both Normal
Blood Detected and Quantified
0.32 ( 0.10-0.74) uM Adult (>18 years old) Male Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
2.1 +/- 1.0 uM Adult (>18 years old) Not Specified Normal
Urine Detected and Quantified
0.79 umol/mmol creatinine Adult (>18 years old) Both Normal
Urine Detected and Quantified
3.8 (2.1-8.3) umol/mmol creatinine Adult (>18 years old) Both Comment Normal
Urine Detected and Quantified
2.4 +/- 4.7 umol/mmol creatinine Adult (>18 years old) Male Normal
Urine Detected and Quantified
3.0 +/- 2.7 umol/mmol creatinine Adult (>18 years old) Female Normal
Urine Detected and Quantified
12.2 +/- 6.2 umol/mmol creatinine Infant (0-1 year old) Both Normal
Urine Detected but not Quantified
Not Applicable Adult (>18 years old) Both Normal
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Cerebrospinal Fluid (CSF) Detected and Quantified 81.5 (46.0-117.0) uM Adult (>18 years old) Both Dihydropyrimidine dehydrogenase (DPD) deficiency
Urine Detected and Quantified 2.4 +/- 1.67 umol/mmol creatinine Adult (>18 years old) Both Hypertension
Urine Detected and Quantified 627.0 umol/mmol creatinine Infant (0-1 year old) Both Dihydropyrimidine dehydrogenase (DPD) deficiency
Urine Detected and Quantified 2.4 +/- 2.00 umol/mmol creatinine Adult (>18 years old) Both Cerebral infarction
Urine Detected and Quantified 2.8 +/- 1.9 umol/mmol creatinine Adult (>18 years old) Both Malignancy
Urine Detected and Quantified 2.7 +/- 1.9 umol/mmol creatinine Adult (>18 years old) Both Liver dysfunction
Urine Detected and Quantified 2.5 +/- 2.00 umol/mmol creatinine Adult (>18 years old) Both Nephrophathy
Associated Disorders and Diseases
Disease References
Dihydropyrimidine dehydrogenase deficiency
  • 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 Link_out
  • 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 Link_out
      Hypertension
      • 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 Link_out
          Associated OMIM IDs
          • 274270 Link_out (Dihydropyrimidine dehydrogenase deficiency)
          • 145500 Link_out (Hypertension)
          DrugBank ID Not Available
          DrugBank Metabolite ID Not Available
          Phenol Explorer Compound ID Not Available
          Phenol Explorer Metabolite ID Not Available
          FoodDB ID FDB021890
          KNApSAcK ID Not Available
          Chemspider ID 629 Link_out
          KEGG Compound ID C00429 Link_out
          BioCyc ID DI-H-URACIL Link_out
          BiGG ID 34956 Link_out
          Wikipedia Link Not Available
          NuGOwiki Link HMDB00076 Link_out
          Metagene Link HMDB00076 Link_out
          METLIN ID 285 Link_out
          PubChem Compound 649 Link_out
          PDB ID DUC Link_out
          ChEBI ID 15901 Link_out
          References
          Synthesis Reference Bhat, 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. 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 Link_out
          2. 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 Link_out
          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 Link_out
          4. 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 Link_out
          5. 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 Link_out
          6. 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 Link_out
          7. 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 Link_out
          8. 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 Link_out
          9. 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 Link_out
          10. Tan BR, McLeod HL: Pharmacogenetic influences on treatment response and toxicity in colorectal cancer. Semin Oncol. 2005 Feb;32(1):113-9. Pubmed: 15726513 Link_out
          11. 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 Link_out
          12. 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 Link_out
          13. 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 Link_out
          14. 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 Link_out

          Enzymes
          Name: Dihydropyrimidinase
          Reactions:
          Dihydrouracil + Water unknown Ureidopropionic acid details
          Gene Name: DPYS
          Uniprot ID: Q14117 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: Dihydropyrimidine dehydrogenase [NADP(+)]
          Reactions:
          Dihydrouracil + NADP unknown Uracil + NADPH details
          Dihydrouracil + NADP unknown Uracil + NADPH + Hydrogen Ion details
          Gene Name: DPYD
          Uniprot ID: Q12882 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA