Fluoropyrimidine Activity (Homo sapiens)
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Description
The main mechanism of 5-FU activation is conversion to fluorodeoxyuridine monophosphate (FdUMP) which inhibits the enzyme thymidylate synthase (TYMS), an important part of the folate-homocysteine cycle and purine and pyrimidine synthesis The conversion of 5-FU to FdUMP can occur via thymidylate phosphorylase (TYMP) to fluorodeoxyuridine (FUDR) and then by the action of thymidine kinase to FdUMP or indirectly via fluorouridine monophosphate (FUMP) or fluroridine (FUR) to fluorouridine diphosphate (FUDP) and then ribonucleotide reductase action to FdUDP and FdUMP. FUDP and FdUDP can also be converted to FUTP and FdUTP and incorporated into RNA and DNA respectively which also contributes to the pharmacodynamic actions of fluoropyrimidines.
Sources: PharmGKB:Fluoropyrimidine Pharmacokinetics, PharmGKB:Fluoropyrimidine Pharmacodynamics, Wikipedia:Fluorouracil
Ontology Tags
Bibliography
| View all 36 references |
- Yuan JH, Cheng JQ, Jiang LY, Ji WD, Guo LF, Liu JJ, Xu XY, He JS, Wang XM, Zhuang ZX; ''Breast cancer resistance protein expression and 5-fluorouracil resistance.; ''Biomed Environ Sci, 2008 - PubMed
- De Angelis PM, Svendsrud DH, Kravik KL, Stokke T; ''Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery.; ''Mol Cancer, 2006 - PubMed
- Wu X, Gu J, Wu TT, Swisher SG, Liao Z, Correa AM, Liu J, Etzel CJ, Amos CI, Huang M, Chiang SS, Milas L, Hittelman WN, Ajani JA; ''Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in esophageal cancer.; ''J Clin Oncol, 2006 - PubMed
- Gusella M, Padrini R; ''G>C SNP of thymidylate synthase with respect to colorectal cancer.; ''Pharmacogenomics, 2007 - PubMed
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External references
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| Name | Type | Database reference |
|---|---|---|
| UCK1 | GeneProduct | 83549 (Entrez Gene) ![]() |
| ABCG2 | GeneProduct | 9429 (Entrez Gene) ![]() |
| Folate Cycle | Pathway | |
| ABCC4 | GeneProduct | 10257 (Entrez Gene) ![]() |
| ABCC3 | GeneProduct | 8714 (Entrez Gene) ![]() |
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