Fluoropyrimidine Activity (Homo sapiens)

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RNA Incorporation Basolateral membrane Reuptake Apical membrane Efflux Drug resistance Liver cell Cancer cell DNA Incorporation 5-fluorouracil (5-FU) Capecitabine FUR 5-dFUR dTMP FUTP FUPA FdUTP TK1 5-hydroxytegafur SLC22A7 DHFR CDA TDG Tegafur Leucovorin DPYD MIR29C FPGS SMUG1 TYMS TYMP MTHFR dUMP DPYS DNA Repair 5-FU FUDP XRCC3 FUMP ERCC2 Folate Cycle 5-FU FBAL FUTP 5,10-Methylenetetrahydrofolate FdUTP GGH CYP2A6 FdUDP 5-FU Dihydrofolate TP53 Apoptosis FUDR FdUMP FdUMP 5-dFCR SLC29A1 UPB1 DHFU UPP1 UPP2 UCK1 UCK2 UMPS PPAT ABCG2 ABCC4 ABCC5 ABCC3 ABCC4 RRM1 RRM2 UPP2 UPP1 TYMP CES1 CES2 Name: Fluoropyrimidine Activity License: CC BY 2.0 Organism: Homo sapiens


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

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Bibliography

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History

View all...
RevisionActionTimeUserComment
95004view 19:10, 26 October 2017EtaglobinTypo in last edit.
95003view 19:07, 26 October 2017EtaglobinFixed dTMP HMDB identifier.
94711view 22:11, 4 October 2017EgonwFixed character encoding.
94708view 21:57, 4 October 2017EgonwReplaced the PubChem CID from the salt with that of the parent compound.
94193view 07:32, 25 August 2017Mkutmonadded missing identifiers
92824view 13:00, 8 July 2017AlexanderPicoChanged other FUTP to PubChem-compound
92823view 12:55, 8 July 2017AlexanderPicoQuick edit to datanode annotation or property
91714view 08:05, 29 March 2017DeSlUpdate with several identifiers (database references) added
84700view 14:22, 15 March 2016KhanspersQuick edit to datanode annotation or property
82222view 20:13, 15 September 2015AlexanderPicoungrouped pathway nodes for biopax conversion
80157view 13:42, 14 May 2015KhanspersAdded mir29C targeting of TDG and correspondning reference
78516view 03:29, 7 January 2015MaintBotadded missing graphIds
73314view 11:31, 19 January 2014AaronCainechanged TYMS cofactor to 5,10 Methylenetetrahydrofolate from 5,10 methenyltetrahydrofolate
69925view 12:50, 11 July 2013AlexanderPicoAdded datanode xrefs
59843view 12:15, 8 March 2013KhanspersUpdated reference for dUMP
54388view 14:16, 28 November 2012EgonwAdded the PubChem Compound ID for FUMP.
54353view 04:50, 28 November 2012EveloSpecify description
54352view 04:09, 28 November 2012EveloAdded Capecitabine ID from Chebi
54351view 03:49, 28 November 2012EveloAdded (Chebi) IDs for 5FU itself
54350view 03:35, 28 November 2012AnweshaPeriodical save, work in progress
47632view 12:47, 31 March 2012AlexanderPicoadded db refs
46342view 16:46, 18 January 2012KhanspersChanged cell shapes back to rounded rectangle
46341view 15:39, 18 January 2012KhanspersRepalced rounded rectangles with rectangles
46305view 10:39, 13 January 2012KhanspersAdded WikiPathways identifiers to pathway nodes
42640view 14:09, 11 April 2011Khanspersfixed lines
41174view 16:42, 1 March 2011MaintBotRemoved redundant pathway information and comments
39389view 15:25, 19 November 2010AlexanderPicoOntology Term : 'hepatocyte' added !
39388view 15:23, 19 November 2010AlexanderPicoOntology Term : 'drug pathway' added !
39387view 15:23, 19 November 2010AlexanderPicoOntology Term : 'cancer' added !
39386view 15:22, 19 November 2010AlexanderPicoupdated cells
38478view 11:18, 17 September 2010AlexanderPicoModified description
38303view 14:48, 30 August 2010AlexanderPicoReverted to version '14:42, 30 August 2010' by AlexanderPico
38302view 14:47, 30 August 2010AlexanderPico
38301view 14:42, 30 August 2010AlexanderPico
38291view 00:56, 30 August 2010AlexanderPicoModified categories
38290view 00:54, 30 August 2010AlexanderPico
38289view 00:47, 30 August 2010AlexanderPicoadding literature refs
38288view 00:22, 30 August 2010AlexanderPicoModified description
38286view 00:18, 30 August 2010AlexanderPicocompleted
38285view 00:02, 30 August 2010AlexanderPicoPeriodical save, work in progress
38283view 23:52, 29 August 2010AlexanderPicoPeriodical save, work in progress
38282view 18:05, 29 August 2010AlexanderPicostarter
38281view 17:56, 29 August 2010AlexanderPicoPeriodical save, work in progress
38280view 17:45, 29 August 2010AlexanderPicoPeriodical save, work in progress
38279view 17:35, 29 August 2010AlexanderPicoPeriodical save, work in progress
38278view 17:25, 29 August 2010AlexanderPicoNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
5,10-MethylenetetrahydrofolateMetabolite97272 (Chemspider)
5-FUMetabolite46345 (ChEBI)
5-dFCRMetabolite10037499 (PubChem-compound)
5-dFURMetaboliteQ1253473 (Wikidata)
5-fluorouracil (5-FU)Metabolite46345 (ChEBI)
5-hydroxytegafurMetabolite
ABCC3GeneProduct8714 (Entrez Gene)
ABCC4GeneProduct10257 (Entrez Gene)
ABCC5GeneProduct10057 (Entrez Gene)
ABCG2GeneProduct9429 (Entrez Gene)
ApoptosisPathwayWP254 (WikiPathways)
CDAGeneProduct978 (Entrez Gene)
CES1GeneProduct1066 (Entrez Gene)
CES2GeneProduct8824 (Entrez Gene)
CYP2A6GeneProduct1548 (Entrez Gene)
CapecitabineMetabolite31348 (ChEBI)
DHFRGeneProduct1719 (Entrez Gene)
DHFUMetabolite121997 (PubChem-compound)
DNA RepairPathwayWP1805 (WikiPathways)
DPYDGeneProduct1806 (Entrez Gene)
DPYSGeneProduct1807 (Entrez Gene)
DihydrofolateMetaboliteHMDB01056 (HMDB)
ERCC2GeneProduct2068 (Entrez Gene)
FBALMetabolite13351 (PubChem-compound)
FPGSGeneProduct2356 (Entrez Gene)
FUDPMetabolite46936877 (PubChem-compound)
FUDRMetaboliteQ5462356 (Wikidata)
FUMPMetabolite796-66-7 (CAS)
FUPAMetabolite151244 (PubChem-compound)
FURMetabolite
FUTPMetabolite10255482 (PubChem-compound)
FdUDPMetabolite53882537 (PubChem-compound)
FdUMPMetabolite8642 (PubChem-compound)
FdUTPMetabolite503023 (PubChem-compound)
Folate CyclePathwayWP176 (WikiPathways)
GGHGeneProduct8836 (Entrez Gene)
LeucovorinMetabolite6006 (PubChem-compound)
MIR29CGeneProductENSG00000284214 (Ensembl)
MTHFRGeneProduct4524 (Entrez Gene)
PPATGeneProduct5471 (Entrez Gene)
RRM1GeneProduct6240 (Entrez Gene)
RRM2GeneProduct6241 (Entrez Gene)
SLC22A7GeneProduct10864 (Entrez Gene)
SLC29A1GeneProduct2030 (Entrez Gene)
SMUG1GeneProduct23583 (Entrez Gene)
TDGGeneProduct6996 (Entrez Gene)
TK1GeneProduct7083 (Entrez Gene)
TP53GeneProduct7157 (Entrez Gene)
TYMPGeneProduct1890 (Entrez Gene)
TYMSGeneProduct7298 (Entrez Gene)
TegafurMetabolite5193 (Chemspider)
UCK1GeneProduct83549 (Entrez Gene)
UCK2GeneProduct7371 (Entrez Gene)
UMPSGeneProduct7372 (Entrez Gene)
UPB1GeneProduct51733 (Entrez Gene)
UPP1GeneProduct7378 (Entrez Gene)
UPP2GeneProduct151531 (Entrez Gene)
XRCC3GeneProduct7517 (Entrez Gene)
dTMPMetaboliteHMDB01227 (HMDB)
dUMPMetaboliteHMDB01409 (HMDB)

Annotated Interactions

<cite>No annotated interactions</cite>