Fluoropyrimidine Activity (Homo sapiens)

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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



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82222view03:13, 16 September 2015AlexanderPicoungrouped pathway nodes for biopax conversion
80157view20:42, 14 May 2015KhanspersAdded mir29C targeting of TDG and correspondning reference
78516view10:29, 7 January 2015MaintBotadded missing graphIds
73314view18:31, 19 January 2014AaronCainechanged TYMS cofactor to 5,10 Methylenetetrahydrofolate from 5,10 methenyltetrahydrofolate
69925view19:50, 11 July 2013AlexanderPicoAdded datanode xrefs
59843view19:15, 8 March 2013KhanspersUpdated reference for dUMP
54388view21:16, 28 November 2012EgonwAdded the PubChem Compound ID for FUMP.
54353view11:50, 28 November 2012EveloSpecify description
54352view11:09, 28 November 2012EveloAdded Capecitabine ID from Chebi
54351view10:49, 28 November 2012EveloAdded (Chebi) IDs for 5FU itself
54350view10:35, 28 November 2012AnweshaPeriodical save, work in progress
47632view19:47, 31 March 2012AlexanderPicoadded db refs
46342view23:46, 18 January 2012KhanspersChanged cell shapes back to rounded rectangle
46341view22:39, 18 January 2012KhanspersRepalced rounded rectangles with rectangles
46305view17:39, 13 January 2012KhanspersAdded WikiPathways identifiers to pathway nodes
42640view21:09, 11 April 2011Khanspersfixed lines
41174view23:42, 1 March 2011MaintBotRemoved redundant pathway information and comments
39389view22:25, 19 November 2010AlexanderPicoOntology Term : 'hepatocyte' added !
39388view22:23, 19 November 2010AlexanderPicoOntology Term : 'drug pathway' added !
39387view22:23, 19 November 2010AlexanderPicoOntology Term : 'cancer' added !
39386view22:22, 19 November 2010AlexanderPicoupdated cells
38478view18:18, 17 September 2010AlexanderPicoModified description
38303view21:48, 30 August 2010AlexanderPicoReverted to version '14:42, 30 August 2010' by AlexanderPico
38302view21:47, 30 August 2010AlexanderPico
38301view21:42, 30 August 2010AlexanderPico
38291view07:56, 30 August 2010AlexanderPicoModified categories
38290view07:54, 30 August 2010AlexanderPico
38289view07:47, 30 August 2010AlexanderPicoadding literature refs
38288view07:22, 30 August 2010AlexanderPicoModified description
38286view07:18, 30 August 2010AlexanderPicocompleted
38285view07:02, 30 August 2010AlexanderPicoPeriodical save, work in progress
38283view06:52, 30 August 2010AlexanderPicoPeriodical save, work in progress
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38278view00:25, 30 August 2010AlexanderPicoNew pathway

External references

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NameTypeDatabase referenceComment
UCK1GeneProduct83549 (Entrez Gene)
ABCG2GeneProduct9429 (Entrez Gene)
dTMPMetaboliteHMDB01056 (HMDB)
ABCC4GeneProduct10257 (Entrez Gene)
ABCC3GeneProduct8714 (Entrez Gene)
5-fluorouracil (5-FU)Metabolite46345 (ChEBI)
SMUG1GeneProduct23583 (Entrez Gene)
5-FUMetabolite46345 (ChEBI)
TK1GeneProduct7083 (Entrez Gene)
TegafurMetabolite5193 (Chemspider)
CYP2A6GeneProduct1548 (Entrez Gene)
TP53GeneProduct7157 (Entrez Gene)
GGHGeneProduct8836 (Entrez Gene)
CapecitabineMetabolite31348 (ChEBI)
UMPSGeneProduct7372 (Entrez Gene)
RRM2GeneProduct6241 (Entrez Gene)
SLC29A1GeneProduct2030 (Entrez Gene)
CES1GeneProduct1066 (Entrez Gene)
DihydrofolateMetaboliteHMDB01056 (HMDB)
CES2GeneProduct8824 (Entrez Gene)
ApoptosisPathwayWP254 (WikiPathways)
CDAGeneProduct978 (Entrez Gene)
TDGGeneProduct6996 (Entrez Gene)
UPP1GeneProduct7378 (Entrez Gene)
FPGSGeneProduct2356 (Entrez Gene)
UPP2GeneProduct151531 (Entrez Gene)
SLC22A7GeneProduct10864 (Entrez Gene)
TYMPGeneProduct1890 (Entrez Gene)
UCK2GeneProduct7371 (Entrez Gene)
PPATGeneProduct5471 (Entrez Gene)
RRM1GeneProduct6240 (Entrez Gene)
TYMSGeneProduct7298 (Entrez Gene)
ABCC5GeneProduct10057 (Entrez Gene)
FUMPMetabolite796-66-7 (CAS)
5,10-MethylenetetrahydrofolateMetabolite97272 (Chemspider)
FUTPMetabolite8430967 (Chemspider)
dUMPMetaboliteHMDB01409 (HMDB)
Folate CyclePathway
DNA RepairPathwayWP1805 (WikiPathways)
ERCC2GeneProduct2068 (Entrez Gene)
XRCC3GeneProduct7517 (Entrez Gene)
DPYDGeneProduct1806 (Entrez Gene)
DHFRGeneProduct1719 (Entrez Gene)
DPYSGeneProduct1807 (Entrez Gene)
MTHFRGeneProduct4524 (Entrez Gene)
UPB1GeneProduct51733 (Entrez Gene)
MIR29CRnaENSG00000207966 (Ensembl)
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