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Human Metabolome Database Version 2.5

 

Showing metabocard for Dihydrouracil (HMDB00076)

Legend: metabolite field enzyme field

Version 2.5
Creation Date 2005-11-16 15:48:42
Update Date 2009-08-12 13:10:52
Accession Number HMDB00076
Secondary Accession Numbers Not Available
Common Name Dihydrouracil
Description 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)
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 IUPAC Name 1,3-diazinane-2,4-dione
Chemical Formula C4H6N2O2
Chemical Structure Structure
Chemical Taxonomy
Kingdom
  • Organic
Super Class
  • Nucleosides and Nucleoside conjugates
Class
  • Pyrimidines and Derivatives
Sub Class
  • Hydroxy pyrimidines
Family
  • Mammalian Metabolite
Species
  • carboxylic acid imide, N-unsubstituted
  • urea
  • heterocyclic compound
Biofunction
  • Component of beta-Alanine metabolism
  • Component of Pantothenate and CoA biosynthesis
  • Component of Pyrimidine metabolism
Application
—
Source
  • Endogenous
Average Molecular Weight 114.103
Monoisotopic Molecular Weight 114.042931
Isomeric SMILES O=C1CCNC(=O)N1
Canonical SMILES O=C1CCNC(=O)N1
KEGG Compound ID C00429 Link Image
BioCyc ID DI-H-URACIL Link Image
BiGG ID 34956 Link Image
Wikipedia Link Not Available
NuGOwiki Link HMDB00076 Link Image
Metagene Link HMDB00076 Link Image
METLIN ID 285 Link Image
PubChem Compound 649 Link Image
PubChem Substance 10391739 Link Image
ChEBI ID 15901 Link Image
CAS Registry Number 504-07-4
InChI Identifier InChI=1/C4H6N2O2/c7-3-1-2-5-4(8)6-3/h1-2H2,(H2,5,6,7,8)
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.
Melting Point (Experimental) 279-281 oC
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 25.9 mg/mL [Predicted by ALOGPS] Calculated using ALOGPS
Physiological Charge 0
State Solid
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP/Hydrophobicity -1.28 [Predicted by ALOGPS]; -1.2 [Predicted by PubChem via XLOGP] Calculated using ALOGPS
Material Safety Data Sheet (MSDS)
MOL File Show
SDF File Show
PDB File Show
2D Structure
3D Structure
Experimental PDB ID Not Available
Experimental 1H NMR Spectrum Download Spectrum
Download FID (Varian)
Show Experimental Conditions Link Image
Experimental 13C NMR Spectrum Not Available
Experimental 13C HSQC Spectrum Download Spectrum
Download FID (Bruker)
Show Experimental Conditions Link Image
Predicted 1H NMR Spectrum Show Image
Show Peaklist
Predicted 13C NMR Spectrum Show Image
Show Peaklist
Mass Spectrum
Low Energy
Download File
Show Experimental Conditions Link Image
Medium Energy
Download File
Show Experimental Conditions Link Image
High Energy
Download File
Show Experimental Conditions Link Image
Simplified TOCSY Spectrum Not Available
BMRB Spectrum Not Available
Cellular Location
  • Nucleus
  • Cytoplasm
Biofluid Location
  • Blood
  • Cerebrospinal Fluid
  • Urine
Tissue Location
Tissue References
Fibroblasts —
Kidney —
Liver —
Concentrations (Normal)
Biofluid Blood
Value 0.32 ( 0.10-0.74) uM
Age Adult:>18 yrs old
Sex Male
Patient information Normal
Comments Not Available
References
  • 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 Link Image]
Biofluid Blood
Value 0.31 (0.02-1.63) uM
Age Adult:>18 yrs old
Sex Female
Patient information Normal
Comments Not Available
References
  • 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 Link Image]
Biofluid Blood
Value 0.31 (0.02-1.63) uM
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
  • 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 Link Image]
Biofluid CSF
Value 2.1 +/- 1.0 uM
Age Adult:>18 yrs old
Sex N/A
Patient information Normal
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 12.2 +/- 6.2 umol/mmol creatinine
Age Infant:0-1 yr old
Sex Both
Patient information Normal
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 0.79 umol/mmol creatinine
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 2.4 +/- 4.7 umol/mmol creatinine
Age Adult:>18 yrs old
Sex Male
Patient information Normal
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 3.0 +/- 2.7 umol/mmol creatinine
Age Adult:>18 yrs old
Sex Female
Patient information Normal
Comments Not Available
References
  • 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 Link Image]
Concentrations (Abnormal)
Biofluid CSF
Value 81.5 (46.0-117.0) uM
Age Adult:>18 yrs old
Sex Both
Condition Dihydropyrimidine dehydrogenase deficiency
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 627.0 umol/mmol creatinine
Age Infant:0-1 yr old
Sex Both
Condition Dihydropyrimidine dehydrogenase deficiency
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 2.4 +/- 1.67 umol/mmol creatinine
Age Adult:>18 yrs old
Sex Both
Condition Hypertension
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 2.4 +/- 2.00 umol/mmol creatinine
Age Adult:>18 yrs old
Sex Both
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 2.8 +/- 1.9 umol/mmol creatinine
Age Adult:>18 yrs old
Sex Both
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 2.7 +/- 1.9 umol/mmol creatinine
Age Adult:>18 yrs old
Sex Both
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 2.5 +/- 2.00 umol/mmol creatinine
Age Adult:>18 yrs old
Sex Both
Comments Not Available
References
  • 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 Link Image]
Associated Disorders
Condition References
Dihydropyrimidine dehydrogenase deficiency
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 Link Image]
OMIM ID
  • 274270 Link Image (Dihydropyrimidine dehydrogenase deficiency)
  • 145500 Link Image (Hypertension)
Pathways
Name SMPDB Link KEGG Link
Beta-Alanine Metabolism SMP00007 Link Image map00410 Link Image
Pyrimidine Metabolism SMP00046 Link Image map00240 Link Image
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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
  10. Tan BR, McLeod HL: Pharmacogenetic influences on treatment response and toxicity in colorectal cancer. Semin Oncol. 2005 Feb;32(1):113-9. [PubMed Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
Metabolic Enzymes
  1. Dihydropyrimidinase
  2. Dihydropyrimidine dehydrogenase [NADP+] precursor
Enzyme 1 [top]
Enzyme 1 ID 5814
Enzyme 1 Name Dihydropyrimidinase
Enzyme 1 Synonyms
  1. DHPase
  2. Hydantoinase
  3. DHP
Enzyme 1 Gene Name DPYS
Enzyme 1 Protein Sequence >Dihydropyrimidinase 
MAAPSRLLIRGGRVVNDDFSEVADVLVEDGVVRALGHDLLPPGGAPAGLRVLDAAGKLVL
PGGIDTHTHMQFPFMGSRSIDDFHQGTKAALSGGTTMIIDFAIPQKGGSLIEAFETWRSW
ADPKVCCDYSLHVAVTWWSDQVKEEMKILVQDKGVNSFKMFMAYKDLYMVTDLELYEAFS
RCKEIGAIAQVHAENGDLIAEGAKKMLALGITGPEGHELCRPEAVEAEATLRAITIASAV
NCPLYIVHVMSKSAAKVIADARRDGKVVYGEPIAASLGTDGTHYWNKEWHHAAHHVMGPP
LRPDPSTPDFLMNLLANDDLTTTGTDNCTFNTCQKALGKDDFTKIPNGVNGVEDRMSVIW
EKGVHSGKMDENRFVAVTSTNAAKIFNLYPRKGRIAVGSDADIVIWDPKGTRTISAKTHH
QAVNFNIFEGMVCHGVPLVTISRGKVVYEAGVFSVTAGDGKFIPRKPFAEYIYKRIKQRD
RTCTPTPVERAPYKGEVATLKSRVTKEDATAGTRKQAHP
Enzyme 1 Number of Residues 519
Enzyme 1 Molecular Weight 56630
Enzyme 1 Theoretical pI 7.28
Enzyme 1 GO Classification
Function
  • catalytic activity
  • hydrolase activity
Process
—
Component
—
Enzyme 1 General Function Nucleotide transport and metabolism
Enzyme 1 Specific Function 5,6-dihydrouracil + H(2)O = 3- ureidopropanoate
Enzyme 1 Pathways
Enzyme 1 Reactions
  • 5,6-dihydrouracil + H2O = 3-ureidopropanoate
Enzyme 1 Pfam Domain Function
Enzyme 1 Signals
  • 1-2
Enzyme 1 Transmembrane Regions Not Available
Enzyme 1 Essentiality Not Available
Enzyme 1 GenBank ID Protein 1330236 Link Image
Enzyme 1 UniProtKB/Swiss-Prot ID Q14117 Link Image
Enzyme 1 UniProtKB/Swiss-Prot Entry Name DPYS_HUMAN Link Image
Enzyme 1 PDB ID Not Available
Enzyme 1 Cellular Location Not Available
Enzyme 1 Gene Sequence >1560 bp 
ATGGCGGCGCCCTCGCGGCTCCTGATCCGCGGGGGTCGCGTGGTCAACGATGACTTCTCG
GAGGTGGCCGACGTGCTGGTGGAGGACGGCGTGGTGCGGGCACTCGGGCACGACCTGCTG
CCTCCCGGGGGCGCTCCTGCGGGGCTGCGGGTCCTCGACGCCGCCGGCAAGCTCGTCCTG
CCCGGAGGCATCGACACACACACGCACATGCAGTTCCCCTTCATGGGCTCGCGGTCCATC
GACGACTTCCACCAGGGCACCAAGGCTGCTCTCTCAGGAGGCACCACCATGATTATTGAT
TTCGCCATTCCTCAGAAAGGTGGCTCCCTCATTGAGGCCTTCGAGACCTGGCGAAGCTGG
GCTGATCCCAAAGTTTGCTGCGACTACAGCCTTCATGTGGCAGTGACGTGGTGGAGTGAC
CAGGTTAAAGAAGAAATGAAAATCCTTGTGCAAGATAAAGGTGTTAACTCTTTCAAGATG
TTTATGGCCTATAAAGATCTGTACATGGTGACAGACCTGGAGCTGTACGAAGCCTTCTCT
CGGTGCAAGGAAATTGGAGCAATTGCCCAGGTCCATGCGGAAAATGGAGACTTAATTGCA
GAGGGAGCAAAGAAGATGTTGGCTCTGGGGATAACAGGCCCTGAGGGCCACGAGCTGTGC
CGCCCAGAGGCAGTGGAGGCAGAGGCCACGCTGAGAGCCATCACCATAGCCAGCGCTGTG
AACTGTCCTCTCTACATTGTGCATGTGATGAGCAAGTCTGCAGCTAAGGTGATAGCGGAT
GCAAGGAGAGATGGGAAGGTGGTCTATGGTGAACCCATAGCAGCCAGTCTTGGCACAGAT
GGCACTCACTACTGGAATAAAGAATGGCACCATGCAGCCCACCATGTCATGGGTCCACCT
TTGCGACCAGACCCCTCAACACCCGACTTCCTCATGAATCTGTTGGCTAATGATGATCTA
ACCACAACAGGGACTGATAACTGCACTTTCAACACCTGCCAGAAAGCTCTTGGGAAGGAT
GATTTTACCAAGATCCCCAATGGGGTGAATGGTGTTGAAGATCGGATGTCCGTAATATGG
GAAAAAGGCGTGCATAGTGGTAAAATGGATGAAAACAGATTTGTGGCAGTTACCAGCACA
AATGCAGCCAAAATTTTTAATCTCTATCCAAGAAAAGGAAGAATAGCTGTAGGATCAGAT
GCTGACATTGTTATTTGGGACCCAAAAGGCACAAGGACTATCTCAGCAAAAACTCATCAT
CAGGCTGTTAACTTCAACATTTTCGAGGGCATGGTTTGCCACGGGGTGCCCCTTGTGACT
ATTTCAAGAGGCAAAGTGGTATATGAAGCCGGAGTGTTCAGTGTCACGGCAGGAGATGGG
AAGTTTATTCCTCGAAAACCATTTGCTGAATATATTTACAAACGAATAAAGCAGCGAGAC
CGGACTTGCACACCTACCCCTGTGGAGCGTGCACCCTATAAGGGAGAAGTCGCCACACTG
AAATCCAGAGTGACAAAAGAAGATGCCACAGCAGGGACCAGGAAACAGGCCCACCCCTGA
Enzyme 1 GenBank Gene ID D78011 Link Image
Enzyme 1 GeneCard ID DPYS Link Image
Enzyme 1 GenAtlas ID DPYS Link Image
Enzyme 1 HGNC ID HGNC:3013 Link Image
Enzyme 1 Chromosome Location 8
Enzyme 1 Locus 8q22
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 General References
  1. Hamajima N, Matsuda K, Sakata S, Tamaki N, Sasaki M, Nonaka M: A novel gene family defined by human dihydropyrimidinase and three related proteins with differential tissue distribution. Gene. 1996 Nov 21;180(1-2):157-63. [PubMed Link Image]
  2. Hamajima N, Kouwaki M, Vreken P, Matsuda K, Sumi S, Imaeda M, Ohba S, Kidouchi K, Nonaka M, Sasaki M, Tamaki N, Endo Y, De Abreu R, Rotteveel J, van Kuilenburg A, van Gennip A, Togari H, Wada Y: Dihydropyrimidinase deficiency: structural organization, chromosomal localization, and mutation analysis of the human dihydropyrimidinase gene. Am J Hum Genet. 1998 Sep;63(3):717-26. [PubMed Link Image]
Enzyme 1 Metabolite References Not Available
Enzyme 2 [top]
Enzyme 2 ID 6002
Enzyme 2 Name Dihydropyrimidine dehydrogenase [NADP+] precursor
Enzyme 2 Synonyms
  1. DPD
  2. DHPDHase
  3. Dihydrouracil dehydrogenase
  4. Dihydrothymine dehydrogenase
Enzyme 2 Gene Name DPYD
Enzyme 2 Protein Sequence >Dihydropyrimidine dehydrogenase [NADP+] precursor 
MAPVLSKDSADIESILALNPRTQTHATLCSTSAKKLDKKHWKRNPDKNCFNCEKLENNFD
DIKHTTLGERGALREAMRCLKCADAPCQKSCPTNLDIKSFITSIANKNYYGAAKMIFSDN
PLGLTCGMVCPTSDLCVGGCNLYATEEGPINIGGLQQFATEVFKAMSIPQIRNPSLPPPE
KMSEAYSAKIALFGAGPASISCASFLARLGYSDITIFEKQEYVGGLSTSEIPQFRLPYDV
VNFEIELMKDLGVKIICGKSLSVNEMTLSTLKEKGYKAAFIGIGLPEPNKDAIFQGLTQD
QGFYTSKDFLPLVAKGSKAGMCACHSPLPSIRGVVIVLGAGDTAFDCATSALRCGARRVF
IVFRKGFVNIRAVPEEMELAKEEKCEFLPFLSPRKVIVKGGRIVAMQFVRTEQDETGKWN
EDEDQMVHLKADVVISAFGSVLSDPKVKEALSPIKFNRWGLPEVDPETMQTSEAWVFAGG
DVVGLANTTVESVNDGKQASWYIHKYVQSQYGASVSAKPELPLFYTPIDLVDISVEMAGL
KFINPFGLASATPATSTSMIRRAFEAGWGFALTKTFSLDKDIVTNVSPRIIRGTTSGPMY
GPGQSSFLNIELISEKTAAYWCQSVTELKADFPDNIVIASIMCSYNKNDWTELAKKSEDS
GADALELNLSCPHGMGERGMGLACGQDPELVRNICRWVRQAVQIPFFAKLTPNVTDIVSI
ARAAKEGGANGVTATNTVSGLMGLKSDGTPWPAVGIAKRTTYGGVSGTAIRPIALRAVTS
IARALPGFPILATGGIDSAESGLQFLHSGASVLQVCSAIQNQDFTVIEDYCTGLKALLYL
KSIEELQDWDGQSPATVSHQKGKPVPRIAELMDKKLPSFGPYLEQRKKIIAENKIRLKEQ
NVAFSPLKRSCFIPKRPIPTIKDVIGKALQYLGTFGELSNVEQVVAMIDEEMCINCGKCY
MTCNDSGYQAIQFDPETHLPTITDTCTGCTLCLSVCPIVDCIKMVSRTTPYEPKRGVPLS
VNPVC
Enzyme 2 Number of Residues 1025
Enzyme 2 Molecular Weight 111375
Enzyme 2 Theoretical pI 7.05
Enzyme 2 GO Classification
Function
  • binding
  • catalytic activity
  • cation binding
  • dihydroorotate dehydrogenase activity
  • dihydroorotate oxidase activity
  • disulfide oxidoreductase activity
  • electron transporter activity
  • ion binding
  • iron ion binding
  • oxidoreductase activity
  • oxidoreductase activity, acting on the CH-CH group of donors
  • oxidoreductase activity, acting on the CH-CH group of donors, oxygen as acceptor
  • transition metal ion binding
  • transporter activity
Process
  • 'de novo' pyrimidine base biosynthesis
  • cellular metabolism
  • electron transport
  • generation of precursor metabolites and energy
  • metabolism
  • nucleobase metabolism
  • nucleobase, nucleoside, nucleotide and nucleic acid metabolism
  • physiological process
  • pyrimidine base biosynthesis
  • pyrimidine base metabolism
Component
  • cell
  • cytoplasm
  • intracellular
  • membrane
Enzyme 2 General Function Amino acid transport and metabolism
Enzyme 2 Specific Function Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil
Enzyme 2 Pathways
Enzyme 2 Reactions
  • 5,6-dihydrouracil + NADP+ = uracil + NADPH + H+
Enzyme 2 Pfam Domain Function
Enzyme 2 Signals
  • None
Enzyme 2 Transmembrane Regions
  • None
Enzyme 2 Essentiality Not Available
Enzyme 2 GenBank ID Protein 558305 Link Image
Enzyme 2 UniProtKB/Swiss-Prot ID Q12882 Link Image
Enzyme 2 UniProtKB/Swiss-Prot Entry Name DPYD_HUMAN Link Image
Enzyme 2 PDB ID 1GTE Link Image
Enzyme 2 PDB File Show
Enzyme 2 3D Structure
Enzyme 2 Cellular Location Not Available
Enzyme 2 Gene Sequence >3078 bp 
ATGGCCCCTGTGCTCAGTAAGGACTCGGCGGACATCGAGAGTATCCTGGCTTTAAATCCT
CGAACACAAACTCATGCAACTCTGTGTTCCACTTCGGCCAAGAAATTAGACAAGAAACAT
TGGAAAAGAAATCCTGATAAGAACTGCTTTAATTGTGAGAAGCTGGAGAATAATTTTGAT
GACATCAAGCACACGACTCTTGGTGAGCGAGGAGCTCTCCGAGAAGCAATGAGATGCCTG
AAATGTGCAGATGCCCCGTGTCAGAAGAGCTGTCCAACTAATCTTGATATTAAATCATTC
ATCACAAGTATTGCAAACAAGAACTATTATGGAGCTGCTAAGATGATATTTTCTGACAAC
CCACTTGGTCTGACTTGTGGAATGGTATGTCCAACCTCTGATCTATGTGTAGGTGGATGC
AATTTATATGCCACTGAAGAGGGACCCATTAATATTGGTGGATTGCAGCAATTTGCTACT
GAGGTATTCAAAGCAATGAGTATCCCACAGATCAGAAATCCTTCGCTGCCTCCCCCAGAA
AAAATGTCTGAAGCCTATTCTGCAAAGATTGCTCTTTTTGGTGCTGGGCCTGCAAGTATA
AGTTGTGCTTCCTTTTTGGCTCGATTGGGGTACTCTGACATCACTATATTTGAAAAACAA
GAATATGTTGGTGGTTTAAGTACTTCTGAAATTCCTCAGTTCCGGCTGCCGTATGATGTA
GTGAATTTTGAGATTGAGCTAATGAAGGACCTTGGTGTAAAGATAATTTGCGGTAAAAGC
CTTTCAGTGAATGAAATGACTCTTAGCACTTTGAAAGAAAAAGGCTACAAAGCTGCTTTC
ATTGGAATAGGTTTGCCAGAACCCAATAAAGATGCCATCTTCCAAGGCCTGACGCAGGAC
CAGGGGTTTTATACATCCAAAGACTTTTTGCCACTTGTAGCCAAAGGCAGTAAAGCAGGA
ATGTGCGCCTGTCACTCTCCATTGCCATCGATACGGGGAGTCGTGATTGTACTTGGAGCT
GGAGACACTGCCTTCGACTGTGCAACATCTGCTCTACGTTGTGGAGCTCGCCGAGTGTTC
ATCGTCTTCAGAAAAGGCTTTGTTAATATAAGAGCTGTCCCTGAGGAGATGGAGCTTGCT
AAGGAAGAAAAGTGTGAATTTCTGCCATTCCTGTCCCCACGGAAGGTTATAGTAAAAGGT
GGGAGAATTGTTGCTATGCAGTTTGTTCGGACAGAGCAAGATGAAACTGGAAAATGGAAT
GAAGATGAAGATCAGATGGTCCATCTGAAAGCCGATGTGGTCATCAGTGCCTTTGGTTCA
GTTCTGAGTGATCCTAAAGTAAAAGAAGCCTTGAGCCCTATAAAATTTAACAGATGGGGT
CTCCCAGAAGTAGATCCAGAAACTATGCAAACTAGTGAAGCATGGGTATTTGCAGGTGGT
GATGTCGTTGGTTTGGCTAACACTACAGTGGAATCGGTGAATGATGGAAAGCAAGCTTCT
TGGTACATTCACAAATACGTACAGTCACAATATGGAGCTTCCGTTTCTGCCAAGCCTGAA
CTACCCCTCTTTTACACTCCTATTGATCTGGTGGACATTAGTGTAGAAATGGCCGGATTG
AAGTTTATAAATCCTTTTGGTCTTGCTAGCGCAACTCCAGCCACCAGCACATCAATGATT
CGAAGAGCTTTTGAAGCTGGATGGGGTTTTGCCCTCACCAAAACTTTCTCTCTTGATAAG
GACATTGTGACAAATGTTTCCCCCAGAATCATCCGGGGAACCACCTCTGGCCCCATGTAT
GGCCCTGGACAAAGCTCCTTTCTGAATATTGAGCTCATCAGTGAGAAAACGGCTGCATAT
TGGTGTCAAAGTGTCACTGAACTAAAGGCTGACTTCCCAGACAACATTGTGATTGCTAGC
ATTATGTGCAGTTACAATAAAAATGACTGGACGGAACTTGCCAAGAAGTCTGAGGATTCT
GGAGCAGATGCCCTGGAGTTAAATTTATCATGTCCACATGGCATGGGAGAAAGAGGAATG
GGCCTGGCCTGTGGGCAGGATCCAGAGCTGGTGCGGAACATCTGCCGCTGGGTTAGGCAA
GCTGTTCAGATTCCTTTTTTTGCCAAGCTGACCCCAAATGTCACTGATATTGTGAGCATC
GCAAGAGCTGCAAAGGAAGGTGGTGCCAATGGCGTTACAGCCACCAACACTGTCTCAGGT
CTGATGGGATTAAAATCTGATGGCACACCTTGGCCAGCAGTGGGGATTGCAAAGCGAACT
ACATATGGAGGAGTGTCTGGGACAGCAATCAGACCTATTGCTTTGAGAGCTGTGACCTCC
ATTGCTCGTGCTCTGCCTGGATTTCCCATTTTGGCTACTGGTGGAATTGACTCTGCTGAA
AGTGGTCTTCAGTTTCTCCATAGTGGTGCTTCCGTCCTCCAGGTATGCAGTGCCATTCAG
AATCAGGATTTCACTGTGATCGAAGACTACTGCACTGGCCTCAAAGCCCTGCTTTATCTG
AAAAGCATTGAAGAACTACAAGACTGGGATGGACAGAGTCCAGCTACTGTGAGTCACCAG
AAAGGGAAACCAGTTCCACGTATAGCTGAACTCATGGACAAGAAACTGCCAAGTTTTGGA
CCTTATCTGGAACAGCGCAAGAAAATCATAGCAGAAAACAAGATTAGACTGAAAGAACAA
AATGTAGCTTTTTCACCACTTAAGAGAAGCTGTTTTATCCCCAAAAGGCCTATTCCTACC
ATCAAGGATGTAATAGGAAAAGCACTGCAGTACCTTGGAACATTTGGTGAATTGAGCAAC
GTAGAGCAAGTTGTGGCTATGATTGATGAAGAAATGTGTATCAACTGTGGTAAATGCTAC
ATGACCTGTAATGATTCTGGCTACCAGGCTATACAGTTTGATCCAGAAACCCACCTGCCC
ACCATAACCGACACTTGTACAGGCTGTACTCTGTGTCTCAGTGTTTGCCCTATTGTCGAC
TGCATCAAAATGGTTTCCAGGACAACACCTTATGAACCAAAGAGAGGCGTACCCTTATCT
GTGAATCCGGTGTGTTAA
Enzyme 2 GenBank Gene ID U09178 Link Image
Enzyme 2 GeneCard ID DPYD Link Image
Enzyme 2 GenAtlas ID DPYD Link Image
Enzyme 2 HGNC ID HGNC:3012 Link Image
Enzyme 2 Chromosome Location 1
Enzyme 2 Locus 1p22
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 General References
  1. Yokota H, Fernandez-Salguero P, Furuya H, Lin K, McBride OW, Podschun B, Schnackerz KD, Gonzalez FJ: cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria. J Biol Chem. 1994 Sep 16;269(37):23192-6. [PubMed Link Image]
  2. Johnson MR, Wang K, Tillmanns S, Albin N, Diasio RB: Structural organization of the human dihydropyrimidine dehydrogenase gene. Cancer Res. 1997 May 1;57(9):1660-3. [PubMed Link Image]
  3. Ogura K, Nishiyama T, Takubo H, Kato A, Okuda H, Arakawa K, Fukushima M, Nagayama S, Kawaguchi Y, Watabe T: Suicidal inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine. Cancer Lett. 1998 Jan 9;122(1-2):107-13. [PubMed Link Image]
  4. Vreken P, Van Kuilenburg AB, Meinsma R, Smit GP, Bakker HD, De Abreu RA, van Gennip AH: A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency. J Inherit Metab Dis. 1996;19(5):645-54. [PubMed Link Image]
  5. Fernandez-Salguero PM, Sapone A, Wei X, Holt JR, Jones S, Idle JR, Gonzalez FJ: Lack of correlation between phenotype and genotype for the polymorphically expressed dihydropyrimidine dehydrogenase in a family of Pakistani origin. Pharmacogenetics. 1997 Apr;7(2):161-3. [PubMed Link Image]
  6. Lu ZH, Zhang R, Diasio RB: Purification and characterization of dihydropyrimidine dehydrogenase from human liver. J Biol Chem. 1992 Aug 25;267(24):17102-9. [PubMed Link Image]
  7. Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH: Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W. Hum Genet. 1997 Dec;101(3):333-8. [PubMed Link Image]
  8. Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH: Identification of novel point mutations in the dihydropyrimidine dehydrogenase gene. J Inherit Metab Dis. 1997 Jul;20(3):335-8. [PubMed Link Image]
Enzyme 2 Metabolite References Not Available