Contents:
Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | - | 1025 | 1p21.3 | DPYD | dihydropyrimidine dehydrogenase | |
| Mouse | - | 1025 | 3 G1 | Dpyd | dihydropyrimidine dehydrogenase | |
| Rat | - | 1025 | 2q41 | Dpyd | dihydropyrimidine dehydrogenase | |
| Previous and Unofficial Names |
| DHPDHase | dihydropyrimidine dehydrogenase [NADP(+)] | DPD |
| Database Links |
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| Alphafold | Q12882 (Hs), Q8CHR6 (Mm), O89000 (Rn) |
| BRENDA | 1.3.1.2 |
| ChEMBL Target | CHEMBL3172 (Hs) |
| Ensembl Gene | ENSG00000188641 (Hs), ENSMUSG00000033308 (Mm), ENSRNOG00000017105 (Rn) |
| Entrez Gene | 1806 (Hs), 99586 (Mm), 81656 (Rn) |
| Human Protein Atlas | ENSG00000188641 (Hs) |
| KEGG Enzyme | 1.3.1.2 |
| KEGG Gene | hsa:1806 (Hs), mmu:99586 (Mm), rno:81656 (Rn) |
| OMIM | 612779 (Hs) |
| Pharos | Q12882 (Hs) |
| RefSeq Nucleotide | NM_000110 (Hs), NM_170778 (Mm), NM_031027 (Rn) |
| RefSeq Protein | NP_000101 (Hs), NP_740748 (Mm), NP_112289 (Rn) |
| UniProtKB | Q12882 (Hs), Q8CHR6 (Mm), O89000 (Rn) |
| Wikipedia | DPYD (Hs) |
| Enzyme Reaction |
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Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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| Gene Expression and Pathophysiology Comments | |
| Genetic deficiency of dihydropyrimidine dehydrogenase activity causes elevated levels of thymine and uracil in the urine (thymine-uraciluria) [1,8-9]. In patients receiving 5-fluorouracil-based chemotherapy DPD deficiency is a pharmacogenetic factor that can dramatically increase the risk of drug-induced toxicity [3,5-6]. |
| General Comments |
| Dihydropyrimidine dehydrogenase (DPD) is required for the first and rate-limiting step of pyrimidine catabolism [7]. In addition to degrading pyrimidines, it also breaks down pyrimidine-based 5-fluorouracil which is the active metabolite of several chemotherapeutic prodrugs (capecitabine, floxuridine, tegafur). DPD inhibitors have been investigated for their potential to enhance 5-fluorouracil levels in the vicinity of tumours being treated with 5-fluorouracil-producing prodrugs [2,4]. |
References
1. Bakkeren JA, De Abreu RA, Sengers RC, Gabreëls FJ, Maas JM, Renier WO. (1984) Elevated urine, blood and cerebrospinal fluid levels of uracil and thymine in a child with dihydrothymine dehydrogenase deficiency. Clin Chim Acta, 140 (3): 247-56. [PMID:6467612]
2. Bellibas SE, Patel I, Chamorey E, Brivet B, Bush ED, Kircher C, Nave S, Banken L, Renée N, Milano G. (2004) Single ascending dose tolerability, pharmacokinetic-pharmacodynamic study of dihydropyrimidine dehydrogenase inhibitor Ro 09-4889. Clin Cancer Res, 10 (7): 2327-35. [PMID:15073108]
3. Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, Schwab M. (2013) Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther, 94 (6): 640-5. [PMID:23988873]
4. Hattori K, Kohchi Y, Oikawa N, Suda H, Ura M, Ishikawa T, Miwa M, Endoh M, Eda H, Tanimura H et al.. (2003) Design and synthesis of the tumor-activated prodrug of dihydropyrimidine dehydrogenase (DPD) inhibitor, RO0094889 for combination therapy with capecitabine. Bioorg Med Chem Lett, 13 (5): 867-72. [PMID:12617910]
5. 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. [PMID:12851836]
6. Schneider HB, Becker H. (2003) Impact of dihydropyrimidine dehydrogenase on 5-fluorouracil treatment in cancer patients. Eur J Med Res, 8 (5): 226-8. [PMID:12844478]
7. Van Kuilenburg AB, Vreken P, Abeling NG, Bakker HD, Meinsma R, Van Lenthe H, De Abreu RA, Smeitink JA, Kayserili H, Apak MY et al.. (1999) Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Hum Genet, 104 (1): 1-9. [PMID:10071185]
8. Vreken P, Van Kuilenburg AB, Meinsma R, Smit GP, Bakker HD, De Abreu RA, van Gennip AH. (1996) 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. [PMID:8892022]
9. Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH. (1997) Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W. Hum Genet, 101 (3): 333-8. [PMID:9439663]
How to cite this page
Nucleotide turnover: dihydropyrimidine dehydrogenase. Last modified on 23/08/2023. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3102.
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