As of late 2007, 5
structures have been solved for this class of enzymes, with
PDB accession codes
1GT8,
1GTE,
1GTH,
1H7W, and
1H7X.
Function
The protein is a
pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of
uracil and
thymidinecatabolism. 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]
Hoff PM, Royce M, Medgyesy D, Brito R, Pazdur R (December 1999). "Oral fluoropoyrimidines". Seminars in Oncology. 26 (6): 640–6.
PMID10606257.
Schneider HB, Becker H (May 2003). "Impact of dihydropyrimidine dehydrogenase on 5-fluorouracil treatment in cancer patients". European Journal of Medical Research. 8 (5): 226–8.
PMID12844478.
Omura K (June 2003). "Clinical implications of dihydropyrimidine dehydrogenase (DPD) activity in 5-FU-based chemotherapy: mutations in the DPD gene, and DPD inhibitory fluoropyrimidines". International Journal of Clinical Oncology. 8 (3): 132–8.
doi:
10.1007/s10147-003-0330-z.
PMID12851836.
S2CID22593228.
Lee W, Lockhart AC, Kim RB, Rothenberg ML (February 2005). "Cancer pharmacogenomics: powerful tools in cancer chemotherapy and drug development". The Oncologist. 10 (2): 104–11.
doi:
10.1634/theoncologist.10-2-104.
PMID15709212.
Dupuis A, Skehel JM, Walker JE (March 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.
PMID1901022.
Eggink G, Engel H, Vriend G, Terpstra P, Witholt B (March 1990). "Rubredoxin reductase of Pseudomonas oleovorans. Structural relationship to other flavoprotein oxidoreductases based on one NAD and two FAD fingerprints". Journal of Molecular Biology. 212 (1): 135–42.
doi:
10.1016/0022-2836(90)90310-I.
PMID2319593.
Tuchman M, Roemeling RV, Hrushesky WA, Sothern RB, O'Dea RF (1989). "Dihydropyrimidine dehydrogenase activity in human blood mononuclear cells". Enzyme. 42 (1): 15–24.
doi:
10.1159/000469002.
PMID2528450.
Lu Z, Zhang R, Diasio RB (November 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 Research. 53 (22): 5433–8.
PMID8221682.
Vreken P, Van Kuilenburg AB, Meinsma R, Smit GP, Bakker HD, De Abreu RA, van Gennip AH (1997). "A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency". Journal of Inherited Metabolic Disease. 19 (5): 645–54.
doi:
10.1007/BF01799841.
PMID8892022.
S2CID10835574.
Johnson MR, Wang K, Tillmanns S, Albin N, Diasio RB (May 1997). "Structural organization of the human dihydropyrimidine dehydrogenase gene". Cancer Research. 57 (9): 1660–3.
PMID9135003.
Fernandez-Salguero PM, Sapone A, Wei X, Holt JR, Jones S, Idle JR, Gonzalez FJ (April 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.
PMID9170156.
Ogura K, Nishiyama T, Takubo H, Kato A, Okuda H, Arakawa K, Fukushima M, Nagayama S, Kawaguchi Y, Watabe T (January 1998). "Suicidal inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine". Cancer Letters. 122 (1–2): 107–13.
doi:
10.1016/S0304-3835(97)00377-7.
PMID9464498.