DPYD
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 articles. [§ 1]
Fluorouracil (5-FU) Activity edit
- ↑ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".
References
- ↑ 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.
- 1 2 "Entrez Gene: DPYD dihydropyrimidine dehydrogenase".
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.
- 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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