Fluoropyrimidine activity (WP3275)

Bos taurus

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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: [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]

Authors

Martina Summer-Kutmon , Friederike Ehrhart , and Eric Weitz

Activity

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Cited In

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Organisms

Bos taurus

Communities

Annotations

Disease Ontology

cancer

Pathway Ontology

drug pathway cancer pathway

Cell Type Ontology

hepatocyte

Participants

Label Type Compact URI Comment
5-fluorouracil (5-FU) Metabolite chebi:46345
Capecitabine Metabolite chebi:31348
dTMP Metabolite hmdb:HMDB0001056
FUTP Metabolite chemspider:8430967
Tegafur Metabolite chemspider:5193
dUMP Metabolite hmdb:HMDB0001409
5-FU Metabolite chebi:46345
FUMP Metabolite cas:796-66-7
5,10-Methylenetetrahydrofolate Metabolite chemspider:97272
Dihydrofolate Metabolite hmdb:HMDB0001056
UPP1 GeneProduct ensembl:ENSBTAG00000008428 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7378
TK1 GeneProduct ensembl:ENSBTAG00000007121 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7083
SLC22A7 GeneProduct ensembl:ENSBTAG00000006350 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10864
ABCC5 GeneProduct ensembl:ENSBTAG00000017666 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10057
DHFR GeneProduct ensembl:ENSBTAG00000007681 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1719
CDA GeneProduct ensembl:ENSBTAG00000006136 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:978
TDG GeneProduct ensembl:ENSBTAG00000021633 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6996
UPP2 GeneProduct ensembl:ENSBTAG00000012801 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:151531
DPYD GeneProduct ensembl:ENSBTAG00000031358 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1806
FPGS GeneProduct ensembl:ENSBTAG00000008994 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2356
ABCC4 GeneProduct ensembl:ENSBTAG00000046611 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10257
SMUG1 GeneProduct ensembl:ENSBTAG00000021974 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:23583
TYMS GeneProduct ensembl:ENSBTAG00000007003 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7298
MTHFR GeneProduct ensembl:ENSBTAG00000020698 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4524
DPYS GeneProduct ensembl:ENSBTAG00000021887 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1807
RRM1 GeneProduct ensembl:ENSBTAG00000013111 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6240
UMPS GeneProduct ensembl:ENSBTAG00000013727 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7372
UCK1 GeneProduct ensembl:ENSBTAG00000010810 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:83549
XRCC3 GeneProduct ensembl:ENSBTAG00000009966 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7517
ERCC2 GeneProduct ensembl:ENSBTAG00000002072 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2068
CES1 GeneProduct ensembl:ENSBTAG00000011021 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1066
UCK2 GeneProduct ensembl:ENSBTAG00000044150 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7371
GGH GeneProduct ensembl:ENSBTAG00000007534 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8836
CYP2A6 GeneProduct ensembl:ENSBTAG00000047815 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1548
ABCG2 GeneProduct ensembl:ENSBTAG00000017704 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9429
TP53 GeneProduct ensembl:ENSBTAG00000001069 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7157
RRM2 GeneProduct ensembl:ENSBTAG00000008216 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6241
SLC29A1 GeneProduct ensembl:ENSBTAG00000015131 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2030
UPB1 GeneProduct ensembl:ENSBTAG00000001325 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:51733
PPAT GeneProduct ensembl:ENSBTAG00000010571 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5471
CES2 GeneProduct ensembl:ENSBTAG00000005093 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8824

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