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Fluoropyrimidine Activity

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: [http://www.pharmgkb.org/do/serve?objId=PA150653776&objCls=Pathway PharmGKB:Fluoropyrimidine Pharmacokinetics], [http://www.pharmgkb.org/do/serve?objId=PA165291507&objCls=Pathway PharmGKB:Fluoropyrimidine Pharmacodynamics], [http://en.wikipedia.org/wiki/Fluorouracil Wikipedia:Fluorouracil]

from WikiPathways source record: WP1601
Type: pathway
Taxonomic scope
organism-specific biosystem

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