DPYD

Dihydropyrimidine dehydrogenase

PDB rendering based on 1gt8.
Identifiers
Symbols DPYD; DHP; DHPDHASE; DPD; MGC132008; MGC70799
External IDs OMIM612779 MGI2139667 HomoloGene85 GeneCards: DPYD Gene
EC number 1.3.1.2
RNA expression pattern
PBB GE DPYD 204646 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1806 99586
Ensembl ENSG00000188641 ENSMUSG00000033308
UniProt Q12882 n/a
RefSeq (mRNA) NM_000110.3 NM_170778.2
RefSeq (protein) NP_000101.2 NP_740748.1
Location (UCSC) Chr 1:
97.54 – 98.39 Mb
Chr 3:
118.27 – 119.14 Mb
PubMed search [1] [2]

Dihydropyrimidine dehydrogenase [NADP+] is an enzyme that in humans is encoded by the DPYD gene.[1][2]

The protein encoded by this gene is a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. Genetic deficiency of this enzyme results in an error in pyrimidine metabolism associated with thymine-uraciluria and an increased risk of toxicity in cancer patients receiving 5-fluorouracil chemotherapy.[2]


Interactive pathway map

Click on genes, proteins and metabolites below to link to respective Wikipedia articles. [3]

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FluoropyrimidineActivity_WP1601 go to article go to article go to article go to article go to article go to article go to article go to article start new article go to article go to article go to article go to article start new article go to article start new article go to article go to article go to article go to article go to article go to article start new article go to article go to article go to article go to article go to article Go to HMDB Go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article
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Fluorouracil (5-FU) Activity edit


References

  1. ^ Takai S, Fernandez-Salguero P, Kimura S, Gonzalez FJ, Yamada K (May 1995). "Assignment of the human dihydropyrimidine dehydrogenase gene (DPYD) to chromosome region 1p22 by fluorescence in situ hybridization". Genomics 24 (3): 613–4. doi:10.1006/geno.1994.1680. PMID 7713523. 
  2. ^ a b "Entrez Gene: DPYD dihydropyrimidine dehydrogenase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1806. 
  3. ^ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601". http://www.wikipathways.org/index.php/Pathway:WP1601. 

Further reading

  • Hoff PM, Royce M, Medgyesy D, et al. (1999). "Oral fluoropoyrimidines". Semin. Oncol. 26 (6): 640–6. PMID 10606257. 
  • Schneider HB, Becker H (2004). "Impact of dihydropyrimidine dehydrogenase on 5-fluorouracil treatment in cancer patients". Eur. J. Med. Res. 8 (5): 226–8. PMID 12844478. 
  • Omura K (2003). "Clinical implications of dihydropyrimidine dehydrogenase (DPD) activity in 5-FU-based chemotherapy: mutations in the DPD gene, and DPD inhibitory fluoropyrimidines". Int. J. Clin. Oncol. 8 (3): 132–8. doi:10.1007/s10147-003-0330-z. PMID 12851836. 
  • Lee W, Lockhart AC, Kim RB, Rothenberg ML (2005). "Cancer pharmacogenomics: powerful tools in cancer chemotherapy and drug development". Oncologist 10 (2): 104–11. doi:10.1634/theoncologist.10-2-104. PMID 15709212. 
  • Lu ZH, Zhang R, Diasio RB (1992). "Purification and characterization of dihydropyrimidine dehydrogenase from human liver". J. Biol. Chem. 267 (24): 17102–9. PMID 1512248. 
  • Porter DJ, Chestnut WG, Merrill BM, Spector T (1992). "Mechanism-based inactivation of dihydropyrimidine dehydrogenase by 5-ethynyluracil". J. Biol. Chem. 267 (8): 5236–42. PMID 1544906. 
  • Dupuis A, Skehel JM, Walker JE (1991). "A homologue of a nuclear-coded iron-sulfur protein subunit of bovine mitochondrial complex I is encoded in chloroplast genomes". Biochemistry 30 (11): 2954–60. doi:10.1021/bi00225a032. PMID 1901022. 
  • Eggink G, Engel H, Vriend G, et al. (1990). "Rubredoxin reductase of Pseudomonas oleovorans. Structural relationship to other flavoprotein oxidoreductases based on one NAD and two FAD fingerprints". J. Mol. Biol. 212 (1): 135–42. doi:10.1016/0022-2836(90)90310-I. PMID 2319593. 
  • Tuchman M, Roemeling RV, Hrushesky WA, et al. (1989). "Dihydropyrimidine dehydrogenase activity in human blood mononuclear cells". Enzyme 42 (1): 15–24. PMID 2528450. 
  • Diasio RB, Beavers TL, Carpenter JT (1988). "Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity". J. Clin. Invest. 81 (1): 47–51. doi:10.1172/JCI113308. PMC 442471. PMID 3335642. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=442471. 
  • Yokota H, Fernandez-Salguero P, Furuya H, et al. (1994). "cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria". J. Biol. Chem. 269 (37): 23192–6. PMID 8083224. 
  • Lu Z, Zhang R, Diasio RB (1993). "Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics, newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy". Cancer Res. 53 (22): 5433–8. PMID 8221682. 
  • Vreken P, Van Kuilenburg AB, Meinsma R, et al. (1997). "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. 19 (5): 645–54. doi:10.1007/BF01799841. PMID 8892022. 
  • Johnson MR, Wang K, Tillmanns S, et al. (1997). "Structural organization of the human dihydropyrimidine dehydrogenase gene". Cancer Res. 57 (9): 1660–3. PMID 9135003. 
  • Fernandez-Salguero PM, Sapone A, Wei X, et al. (1997). "Lack of correlation between phenotype and genotype for the polymorphically expressed dihydropyrimidine dehydrogenase in a family of Pakistani origin". Pharmacogenetics 7 (2): 161–3. doi:10.1097/00008571-199704000-00012. PMID 9170156. 
  • Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH (1997). "Identification of novel point mutations in the dihydropyrimidine dehydrogenase gene". J. Inherit. Metab. Dis. 20 (3): 335–8. doi:10.1023/A:1005357307122. PMID 9266349. 
  • Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH (1998). "Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W". Hum. Genet. 101 (3): 333–8. doi:10.1007/s004390050637. PMID 9439663. 
  • Ogura K, Nishiyama T, Takubo H, et al. (1998). "Suicidal inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine". Cancer Lett. 122 (1–2): 107–13. doi:10.1016/S0304-3835(97)00377-7. PMID 9464498. 

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