Information on EC 2.4.2.4 - thymidine phosphorylase and Organism(s) Homo sapiens

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
2.4.2.4
-
RECOMMENDED NAME
GeneOntology No.
thymidine phosphorylase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
SN2-type catalytic mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pentosyl group transfer
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
pyrimidine deoxyribonucleosides degradation
-
-
pyrimidine metabolism
-
-
Pyrimidine metabolism
-
-
Drug metabolism - other enzymes
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
thymidine:phosphate deoxy-alpha-D-ribosyltransferase
The enzyme in some tissues also catalyses deoxyribosyltransferase reactions of the type catalysed by EC 2.4.2.6, nucleoside deoxyribosyltransferase.
CAS REGISTRY NUMBER
COMMENTARY hide
9030-23-3
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1-(tetrahydro-2-furanyl)-5-fluorouracil + phosphate
?
show the reaction diagram
2'-deoxy-5-nitrouridine + phosphate
5-nitrouracil + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
3-fluorothymidine + phosphate
3-fluorothymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5'-fluorothymidine + phosphate
thymine + 5-fluoro-2,5-dideoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5-fluorouridine + phosphate
5-fluorouracil + 5-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5-fluorouridine + phosphate
5-fluorouracil + 5-deoxyribose-1-phosphate
show the reaction diagram
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxyribose-1-phosphate
show the reaction diagram
5-fluorouracil + 2-deoxy-alpha-D-ribose 1-phosphate
5-fluoro-2'-deoxyuridine + phosphate
show the reaction diagram
5-fluorouridine + phosphate
5-fluorouracil + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-nitro-2'-deoxyuridine + phosphate
5-nitrouracil + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-nitro-2'-deoxyuridine + phosphate
5-nitrouridine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
bromodeoxyuridine + phosphate
bromouracil + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
?
deoxythymidine + phosphate
thymidine + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
?
deoxythymidine + phosphate
thymidine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
deoxyuridine + phosphate
uracil + 2-deoxy-D-ribose
show the reaction diagram
deoxyuridine + phosphate
uracil + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
fluorodeoxyuridine + phosphate
fluorouracil + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
?
iododeoxyuridine + phosphate
iodouracil + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
?
thymidine + arsenate
?
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
thymidine + phosphate
thymine + alpha-D-deoxyribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
uridine + phosphate
uracil + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
5-fluorouracil + 2-deoxy-alpha-D-ribose 1-phosphate
5-fluoro-2'-deoxyuridine + phosphate
show the reaction diagram
-
the enzyme converts 5-fluorouracil to 5-fluoro-2'-deoxyuridine, activating the prodrug, overview. This action can only take place if there is enough co-substrate. 5-Fluorouracil prodrugs and metabolism, detailed overview
5-fluoro-2'-deoxyuridine is further converted by thymidine kinase to 5-fluoro-2'-deoxyuridine 5'-monophosphate
-
?
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
additional information
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(4xi)-2',3'-O-[(1R)-2-carboxyethylidene]-5-methylcytidine
-
-
(4xi)-5-methyl-2',3'-O-[(1R)-2-phosphonoethylidene]cytidine
-
-
(R)-(1-fluoro-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propan-2-yloxy)methylphosphonic phosphoric anhydride
-
strong inhibitory effect
(R)-1-[3-fluoro-2-(phosphonomethoxy)-propyl]thymine
-
at 0.01 mM, 82% inhibition of V79 cell-expressed thymidine phosphorylase, 56% inhibition of thymidine phosphorylase from placenta
(R)-1-[3-fluoro-2-(phosphonomethoxy)propyl]thymine
-
efficient inhibitor
(R)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]thymine
-
at 0.01 mM, 84% inhibition of V79 cell-expressed thymidine phosphorylase, 84% inhibition of thymidine phosphorylase from placenta
(S)-(1-fluoro-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propan-2-yloxy)methylphosphonic phosphoric anhydride
-
strong inhibitory effect
(S)-1-[3-fluoro-2-(phosphonomethoxy)propyl]thymine
-
efficient inhibitor
([(1R)-2-fluoro-1-[(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
-
([(1R)-2-fluoro-1-[(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
; at 0.01 mM, complete inhibition of V79 cell-expressed thymidine phosphorylase
([(1R)-2-fluoro-1-[(5-methyl-2,6-dioxotetrahydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
low inhibitory effect
([(1R)-2-hydroxy-1-[(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
; at 0.01 mM, 91% inhibition of V79 cell-expressed thymidine phosphorylase, 79% inhibition of thymidine phosphorylase from placenta
([(1S)-2-fluoro-1-[(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
-
([(1S)-2-fluoro-1-[(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
; at 0.01 mM, complete inhibition of V79 cell-expressed thymidine phosphorylase
([(1S)-2-fluoro-1-[(5-methyl-2,6-dioxotetrahydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
low inhibitory effect
([(1S)-2-hydroxy-1-[(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
; at 0.01 mM, complete of V79 cell-expressed thymidine phosphorylase, 95% inhibition of thymidine phosphorylase from placenta
([2,2,2-trifluoro-1-[(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
-
([[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl]oxy]methyl)phosphonic acid
-
-
1-(8-phosphonooctyl)-6-amino-5-bromouracil
-
competitive
1-(8-phosphonooctyl)-7-deazaxanthine
-
competitive
1-[(R)-3-fluoro-2-(phosphonomethoxy)propyl]thymine
-
-
1-[2-(phosphonomethoxy)ethyl]thymine
-
at 0.01 mM, complete inhibition of V79 cell-expressed thymidine phosphorylase, 85% inhibition of thymidine phosphorylase from placenta
2,7-bis(methylsulfanyl)[1,2,4]triazolo[1,5-a][1,3,5]triazin-5(4H)-one
-
-
2-(3-bromophenyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
2-(3-methylphenyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
2-(4-bromo-3-methylphenyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
2-(4-bromophenyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
2-(4-methylphenyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
2-(benzylsulfanyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
2-(furan-2-yl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
2-(methylsulfanyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
2-(methylsulfanyl)-7-sulfanylidene-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5(4H)-one
-
-
2-(methylsulfanyl)[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7(4H,6H)-dione
-
-
2-(pyridin-2-yl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
2-benzyl-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
2-deoxy-L-ribose
-
-
2-mercapto-7H-pyrrolo[2,3-d]pyrimidin-4(3H)-one
-
-
2-phenyl-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
2-phenyl-7-sulfanylidene-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5(4H)-one
-
-
2-phenyl[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7(4H,6H)-dione
-
-
2-[(2-phenylethyl)sulfanyl]-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
2-[(3-phenylpropyl)sulfanyl]-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
3-benzoyl-5-chloropyrimidine-2,4(1H,3H)-dione
-
-
4,6-dihydroxy-5-nitropyrimidine
-
0.1 mM, competitive
5'-O-trityl-inosine
5'-O-tritylinosine
5-amino-6-chlorouracil
-
-
5-benzyl-6-chloropyrimidine-2,4(1H,3H)-dione
-
-
5-benzylacyclouridine
-
-
5-bromo-6-(3'-methylimidazol-1-yl)uracil
-
IC50: 0.038 mM
5-bromo-6-amino-uracil
-
enzyme inhibition results in a significant increase in basal and oxidative stress-induced apoptosis, the effect is abrogated by supplementation with 2-deoxy-D-ribose-1-phosphate
5-bromo-6-aminouracil
-
-
5-bromo-6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.16 mM
5-bromo-6-[(3-methylimidazol-1-yl)methyl]uracil
-
IC50: 0.017 mM
5-bromo-6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.181 mM
5-Bromouracil
-
0.1 mM, competitive
5-butyl-6-chloropyrimidine-2,4(1H,3H)-dione
-
-
5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidinedione hydrochloride
-
-
5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4-(1H,3H)-pyrimidine
-
-
5-chloro-6-(3'-methylimidazol-1-yl)uracil
-
IC50: 0.035 mM
5-chloro-6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.115 mM
5-chloro-6-[(3-methylimidazol-1-yl)methyl]uracil
-
IC50: 0.018 mM
5-chloro-6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.2 mM
5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride
-
-
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl] uracil hydrochloride
-
-
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracil
-
-
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracil hydrochloride
-
-
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracilhydrochloride
-
-
5-chloro-6-[1-(imminopyrrolidinyl)methyl]uracil hydrochloride
5-ethyl-1-[(R)-3-fluoro-2-(phosphonomethoxy)propyl]uracil
-
-
5-ethyl-1-[(R)-3-hydroxy-2-(phosphonomethoxy)propyl]uracil
-
-
5-ethyl-1-[(S)-3-fluoro-2-(phosphonomethoxy)propyl]uracil
-
-
5-fluoro-6-[(2-aminoimidazol-1-yl)methyl]uracil
-
i.e. AIFU, synthesis, overview, uncompetitive with respect to phosphate, acts as transition state analogs, mimicking the anionic thymine leaving group anchored by their protonated side chains to the enzyme-bound phosphate by electrostatic and H-bonding interactions, modeling of ligand binding at the active site, overview
5-fluorouracil
-
0.1 mM, competitive
5-Iodouracil
-
His116 directly interacts with the inhibitor via its NE2 group, enzyme binding structure, overview
5-methyluridine
-
-
5-Nitrouracil
-
0.1 mM, competitive
5-phenyl-6-pyrrolidin-1-ylpyrimidine-2,4(1H,3H)-dione
-
-
5-sulfanylidene-2-(thiophen-2-yl)-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
-
-
5-[(1E)-but-1-en-1-yl]-6-chloropyrimidine-2,4(1H,3H)-dione
-
-
6-(2-aminoethyl)amine-5-chlorouracil
-
AEAC
6-(3-methylimidazol-1-yl)uracil
-
IC50: 0.110 mM
6-(4-phenlybutylamino)uracil
-
PBAU, 50% inhibition at 0.03 mM
6-amino-5-bromouracil
-
-
6-amino-5-chlorouracil
6-aminouracil
-
0.1 mM, competitive
6-benzyl-2-thiouracil
-
0.1 mM, mixed inhibition
6-bromo-5-phenylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-(1-methylethenyl)pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-(2-naphthyl)pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-(2-thienyl)pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-(3,5-dimethylphenyl)pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-(4-fluorophenyl)pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-cyclohex-1-en-1-ylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-cyclopent-1-en-1-yluracil
-
-
6-chloro-5-ethylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-heptylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-hexylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-pentylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-phenylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-propylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-pyridin-3-ylpyrimidine-2,4(1H,3H)-dione hydrochloride
-
-
6-chloro-5-[(1E)-1-ethylprop-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-[(1E)-pent-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-[(1E)-prop-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
-
-
6-fluoro-5-phenylpyrimidine-2,4(1H,3H)-dione
-
-
6-methyl-5-phenylpyrimidine-2,4(1H,3H)-dione
-
-
6-[(2'-aminoimidazol-1'-yl)methyl]-5-bromouracil
-
IC50: 0.000019 mM
6-[(2'-aminoimidazol-1'-yl)methyl]-5-chlorouracil
-
IC50: below 0.000049 mM
6-[(2'-aminoimidazol-1'-yl)methyl]uracil
-
IC50: 0.0001 mM
6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.2577 mM
6-[(2-aminoethyl)amino]-5-phenylpyrimidine-2,4(1H,3H)-dione
-
-
6-[(3-methylimidazol-1-yl)methyl]thymine
-
IC50: 0.06 mM
6-[(3-methylimidazol-1-yl)methyl]uracil
-
IC50: 0.042 mM
6-[(4'-aminoimidazol-1'-yl)methyl]-5-bromouracil
-
IC50: 0.041 mM
6-[(4'-aminoimidazol-1'-yl)methyl]-5-chlorouracil
-
IC50: 0.026 mM
6-[(4'-aminoimidazol-1'-yl)methyl]uracil
-
IC50: 0.143 mM
6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.5 mM
7-(methylsulfanyl)-2-phenyl[1,2,4]triazolo[1,5-a][1,3,5]triazin-5(4H)-one
-
-
7-deazaxanthine
9-[8-phosphonooctyl]-7-deazaxanthine
-
-
allyloxymethylthymine
-
0.1 mM, uncompetitive
aurothioglucose
-
the expression of tyhmidine phosphorylase mRNA is significantly decreased by stimulation with aurothioglucose
dexamethasone
-
the expression of tyhmidine phosphorylase mRNA is significantly decreased by stimulation with dexamethasone
diethyl ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)(difluoro)methyl)phosphonate
-
-
diethyl ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate
-
-
diethyl ((2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate
-
-
diethyl (2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]benzyl)phosphonate
-
-
diethyl ([2-(hydroxymethyl)cyclopent-1-en-1-yl]methyl)phosphonate
-
-
diethyl [(Z)-4-(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)but-2-en-1-yl]phosphonate
-
-
diethyl [(Z)-4-hydroxybut-2-en-1-yl]phosphonate
-
-
diethyl [2-(hydroxymethyl)benzyl]phosphonate
-
-
disodium ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)(difluoro)methyl)phosphonate
-
-
disodium ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate
-
-
disodium ((2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate
-
-
disodium (2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]benzyl)phosphonate
-
-
disodium [(Z)-4-(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)but-2-en-1-yl]phosphonate
-
-
hydrogen [[(1R,2S,4S)-2-(hydroxymethyl)-4-(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)pyrrolidinium-1-yl]methyl]phosphonate
-
-
KIN56
-
IC50: 0.351 mM
KIN59
-
i.e. 5'-O-tritylinosine, noncompetitive inhibition
-
NSC 65043
-
IC50: 0.077 mM
p-chloromercuribenzoate
-
above 0.01 mM
prostaglandin E2
-
-
thymidine
-
substrate inhibition
thymidine phosphorylase inhibitor
-
-
-
Uracil
-
inhibits activity in turmor tissue, but not in normal tissue
Urea
-
inhibition at high concentration, 4 M, stimulation at low concentration
uridine
-
-
xanthine
-
-
[(2S,3aR,4R,6R,6aR)-4-(5-chloro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-6-(hydroxymethyl)tetrahydrofuro[3,4-d][1,3]dioxol-2-yl]phosphonic acid
-
-
[(2S,4R,5S)-5-(2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxy-1,3-oxazolidin-2-yl]phosphonic acid
-
-
[(3aR,4R,6R,6aR)-4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-6-(hydroxymethyl)tetrahydrofuro[3,4-d][1,3]dioxol-2-yl]phosphonic acid
-
-
[(3aR,4R,6R,6aR)-4-(hydroxymethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuro[3,4-d][1,3]dioxol-2-yl]phosphonic acid
-
-
[8-(2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-1-yl)octyl]phosphonic acid
-
no antitumor activity found with CCRF-CEM T-lymphoblastoid cells, human promyelocytic leukemia HL-60 cells, human cervix carcinoma HeLa S3 cells
[8-(2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimidin-1-yl)octyl]phosphonic acid
-
no antitumor activity found with CCRF-CEM T-lymphoblastoid cells, human promyelocytic leukemia HL-60 cells, human cervix carcinoma HeLa S3 cells
[[(1R)-2-(5-ethyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-1-(fluoromethyl)ethoxy]methyl]phosphonic acid
-
-
[[(2R,3aR,6aR)-6-(4-amino-5-methyl-2-oxopyrimidin-1(2H)-yl)-4-(hydroxymethyl)hexahydrofuro[3,4-b]furan-2-yl]methyl]phosphonic acid
-
-
[[(2S,3aR,6aR)-6-(4-amino-5-methyl-2-oxopyrimidin-1(2H)-yl)-4-(hydroxymethyl)hexahydrofuro[3,4-b]furan-2-yl]methyl]phosphonic acid
-
-
[[(2S,3aR,6aS)-4-(4-amino-5-methyl-2-oxopyrimidin-1(2H)-yl)-6-(hydroxymethyl)hexahydrofuro[3,4-b]furan-2-yl]methyl]phosphonic acid
-
-
[[(3S,4R)-3-hydroxy-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonyl]phosphonic acid
-
-
[[2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy]methyl]phosphonic acid
-
-
[[2-(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)ethoxy]methyl]phosphonic acid
-
; at 0.01 mM, complete inhibition of V79 cell-expressed thymidine phosphorylase, 82% inhibition of thymidine phosphorylase from placenta
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cyclophosphamide
docetaxel
-
induces thymidine phosphorylase expression
doxorubicin
-
thymidine phosphorylase expression is upregulated after treatment with 60 mg/m2 doxorubicin
epirubicin
-
thymidine phosphorylase expression is upregulated after treatment with 75 mg/m2 epirubicin
interferon alpha
-
interferon alpha2b
-
induces thymidine phosphorylase mRNA and protein expression in a dose-dependent manner
-
interferon beta
-
causes a rapid and transient increase of thymidine phosphorylase expression
-
interferon gamma
-
causes a rapid and transient increase of thymidine phosphorylase expression
-
Interleukin-1beta
-
the expression of tyhmidine phosphorylase mRNA is significantly increased by stimulation with interleukin-1beta
-
mitomycin C
-
induces thymidine phosphorylase expression
paclitaxel
Tumor necrosis factor alpha
-
Urea
-
stimulates at low concentration, inhibits at high concentration, 4 M
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
13.3
1-(Tetrahydro-2-furanyl)-5-fluorouracil
-
-
1.72
5'-deoxy-5-fluorouridine
-
-
0.16
5-nitro-2'-deoxyuridine
0.00064 - 0.107
phosphate
0.043 - 9.3
thymidine
0.414 - 9.828
thymine
47.6
uridine
-
-
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2.88
5-nitro-2'-deoxyuridine
-
pH 7.4, 25°C
0.157 - 8.2
thymidine
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
67
phosphate
-
at pH 7.5 at 37°C
109
thymidine
-
at pH 7.5 at 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0435
(4xi)-2',3'-O-[(1R)-2-carboxyethylidene]-5-methylcytidine
-
-
0.000236
(4xi)-5-methyl-2',3'-O-[(1R)-2-phosphonoethylidene]cytidine
-
-
0.021 - 0.211
4,6-dihydroxy-5-nitropyrimidine
0.0002 - 0.00455
5-benzyl-6-chloropyrimidine-2,4(1H,3H)-dione
0.0011 - 0.006
5-Bromouracil
0.00103 - 0.00165
5-butyl-6-chloropyrimidine-2,4(1H,3H)-dione
0.017
5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidinedione hydrochloride
-
in 50 mM Tris, 1 mM EDTA, pH 7.4, at 37°C
0.0000013 - 0.0000021
5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4-(1H,3H)-pyrimidine
0.000002
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl] uracil hydrochloride
-
-
0.00002
5-chloro-6-[1-(imminopyrrolidinyl)methyl]uracil hydrochloride
-
-
0.000017
5-fluoro-6-[(2-aminoimidazol-1-yl)methyl]uracil
-
-
0.043 - 0.0728
5-fluorouracil
0.48
5-Iodouracil
-
-
0.017
5-methyluridine
-
pH 6.0, recombinant enzyme
0.0051 - 0.0253
5-Nitrouracil
0.02
5-phenyl-6-pyrrolidin-1-ylpyrimidine-2,4(1H,3H)-dione
-
Km above 0.02 mM, enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37°C; Km above 0.02 mM, enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37°C
0.00063 - 0.00092
5-[(1E)-but-1-en-1-yl]-6-chloropyrimidine-2,4(1H,3H)-dione
0.000165
6-(2-aminoethyl)amine-5-chlorouracil
-
-
0.0034
6-amino-5-chlorouracil
-
-
0.088 - 0.13
6-aminouracil
0.075 - 0.137
6-benzyl-2-thiouracil
0.00121
6-bromo-5-phenylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37°C; enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37°C
0.00334 - 0.0051
6-chloro-5-(1-methylethenyl)pyrimidine-2,4(1H,3H)-dione
0.00394 - 0.00459
6-chloro-5-(2-naphthyl)pyrimidine-2,4(1H,3H)-dione
0.00028 - 0.00054
6-chloro-5-(2-thienyl)pyrimidine-2,4(1H,3H)-dione
0.00127 - 0.00174
6-chloro-5-(3,5-dimethylphenyl)pyrimidine-2,4(1H,3H)-dione
0.00071 - 0.00097
6-chloro-5-(4-fluorophenyl)pyrimidine-2,4(1H,3H)-dione
0.00042 - 0.00075
6-chloro-5-cyclohex-1-en-1-ylpyrimidine-2,4(1H,3H)-dione
0.0002 - 0.00029
6-chloro-5-cyclopent-1-en-1-yluracil
0.02
6-chloro-5-ethylpyrimidine-2,4(1H,3H)-dione
-
Km above 0.02 mM, enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37°C; Km above 0.02 mM, enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37°C
0.0016 - 0.00465
6-chloro-5-heptylpyrimidine-2,4(1H,3H)-dione
0.00106 - 0.00179
6-chloro-5-hexylpyrimidine-2,4(1H,3H)-dione
0.00309 - 0.00367
6-chloro-5-pentylpyrimidine-2,4(1H,3H)-dione
0.0004 - 0.00043
6-chloro-5-phenylpyrimidine-2,4(1H,3H)-dione
0.00402 - 0.00581
6-chloro-5-propylpyrimidine-2,4(1H,3H)-dione
0.00301 - 0.00399
6-chloro-5-pyridin-3-ylpyrimidine-2,4(1H,3H)-dione hydrochloride
0.00049 - 0.00091
6-chloro-5-[(1E)-1-ethylprop-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
0.00041 - 0.00091
6-chloro-5-[(1E)-pent-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
0.00117 - 0.00121
6-chloro-5-[(1E)-prop-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
0.00047 - 0.0005
6-fluoro-5-phenylpyrimidine-2,4(1H,3H)-dione
0.02
6-methyl-5-phenylpyrimidine-2,4(1H,3H)-dione
-
Km above 0.02 mM, enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37°C; Km above 0.02 mM, enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37°C
0.02
6-[(2-aminoethyl)amino]-5-phenylpyrimidine-2,4(1H,3H)-dione
-
Km above 0.02 mM, enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37°C; Km above 0.02 mM, enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37°C
0.127 - 0.1286
allyloxymethylthymine
0.005
hydrogen [[(1R,2S,4S)-2-(hydroxymethyl)-4-(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)pyrrolidinium-1-yl]methyl]phosphonate
-
-
2 - 5
NSC 65043
-
-
0.00002
thymidine phosphorylase inhibitor
-
-
-
0.158
Uracil
-
tumor tissue
0.013
uridine
-
pH 6.0, recombinant enzyme
0.00077
[(2S,3aR,4R,6R,6aR)-4-(5-chloro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-6-(hydroxymethyl)tetrahydrofuro[3,4-d][1,3]dioxol-2-yl]phosphonic acid
-
-
0.004
[(2S,4R,5S)-5-(2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxy-1,3-oxazolidin-2-yl]phosphonic acid
-
-
0.005
[(3aR,4R,6R,6aR)-4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-6-(hydroxymethyl)tetrahydrofuro[3,4-d][1,3]dioxol-2-yl]phosphonic acid
-
-
0.01
[(3aR,4R,6R,6aR)-4-(hydroxymethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuro[3,4-d][1,3]dioxol-2-yl]phosphonic acid
-
-
0.0334
[[(2R,3aR,6aR)-6-(4-amino-5-methyl-2-oxopyrimidin-1(2H)-yl)-4-(hydroxymethyl)hexahydrofuro[3,4-b]furan-2-yl]methyl]phosphonic acid
-
-
0.00105
[[(2S,3aR,6aR)-6-(4-amino-5-methyl-2-oxopyrimidin-1(2H)-yl)-4-(hydroxymethyl)hexahydrofuro[3,4-b]furan-2-yl]methyl]phosphonic acid
-
-
0.00803
[[(2S,3aR,6aS)-4-(4-amino-5-methyl-2-oxopyrimidin-1(2H)-yl)-6-(hydroxymethyl)hexahydrofuro[3,4-b]furan-2-yl]methyl]phosphonic acid
-
-
0.01
[[(3S,4R)-3-hydroxy-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonyl]phosphonic acid
-
-
additional information
additional information
-
inhibition kinetics, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1
2,7-bis(methylsulfanyl)[1,2,4]triazolo[1,5-a][1,3,5]triazin-5(4H)-one
Homo sapiens;
-
IC50 above 0.1 mM, pH and temperature not specified in the publication
0.03178
2-(3-bromophenyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.03442
2-(3-methylphenyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.01309
2-(4-bromo-3-methylphenyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.02206
2-(4-bromophenyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.03158
2-(4-methylphenyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.05538
2-(benzylsulfanyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.03154
2-(furan-2-yl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.05167
2-(methylsulfanyl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.1
2-(methylsulfanyl)-7-sulfanylidene-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5(4H)-one
Homo sapiens;
-
IC50 above 0.1 mM, pH and temperature not specified in the publication
0.1
2-(methylsulfanyl)[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7(4H,6H)-dione
Homo sapiens;
-
IC50 above 0.1 mM, pH and temperature not specified in the publication
0.02453
2-(pyridin-2-yl)-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.04332
2-benzyl-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.03956
2-phenyl-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.1
2-phenyl-7-sulfanylidene-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5(4H)-one
Homo sapiens;
-
IC50 above 0.1 mM, pH and temperature not specified in the publication
0.1
2-phenyl[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7(4H,6H)-dione
Homo sapiens;
-
IC50 above 0.1 mM, pH and temperature not specified in the publication
0.05988
2-[(2-phenylethyl)sulfanyl]-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.05925
2-[(3-phenylpropyl)sulfanyl]-5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.067
5'-O-trityl-inosine
0.038
5-bromo-6-(3'-methylimidazol-1-yl)uracil
Homo sapiens;
-
IC50: 0.038 mM
0.16
5-bromo-6-[(2'-nitroimidazol-1'-yl)methyl]uracil
Homo sapiens;
-
IC50: 0.16 mM
0.017
5-bromo-6-[(3-methylimidazol-1-yl)methyl]uracil
Homo sapiens;
-
IC50: 0.017 mM
0.181
5-bromo-6-[(4'-nitroimidazol-1'-yl)methyl]uracil
Homo sapiens;
-
IC50: 0.181 mM
0.035
5-chloro-6-(3'-methylimidazol-1-yl)uracil
Homo sapiens;
-
IC50: 0.035 mM
0.115
5-chloro-6-[(2'-nitroimidazol-1'-yl)methyl]uracil
Homo sapiens;
-
IC50: 0.115 mM
0.018
5-chloro-6-[(3-methylimidazol-1-yl)methyl]uracil
Homo sapiens;
-
IC50: 0.018 mM
0.2
5-chloro-6-[(4'-nitroimidazol-1'-yl)methyl]uracil
Homo sapiens;
-
IC50: 0.2 mM
0.000035
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracil
Homo sapiens;
-
-
0.000023
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracilhydrochloride
Homo sapiens;
-
in 0.1 M potassium phosphate buffer (pH 7.4), at 25°C
0.03095
5-sulfanylidene-2-(thiophen-2-yl)-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.05813
5-sulfanylidene-5,6-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.11
6-(3-methylimidazol-1-yl)uracil
Homo sapiens;
-
IC50: 0.110 mM
0.0068
6-amino-5-bromouracil
Homo sapiens;
-
in 0.1 M potassium phosphate buffer (pH 7.4), at 25°C
0.000019
6-[(2'-aminoimidazol-1'-yl)methyl]-5-bromouracil
Homo sapiens;
-
IC50: 0.000019 mM
0.000049
6-[(2'-aminoimidazol-1'-yl)methyl]-5-chlorouracil
Homo sapiens;
-
IC50: below 0.000049 mM
0.0001
6-[(2'-aminoimidazol-1'-yl)methyl]uracil
Homo sapiens;
-
IC50: 0.0001 mM
0.2577
6-[(2'-nitroimidazol-1'-yl)methyl]uracil
Homo sapiens;
-
IC50: 0.2577 mM
0.06
6-[(3-methylimidazol-1-yl)methyl]thymine
Homo sapiens;
-
IC50: 0.06 mM
0.042
6-[(3-methylimidazol-1-yl)methyl]uracil
Homo sapiens;
-
IC50: 0.042 mM
0.041
6-[(4'-aminoimidazol-1'-yl)methyl]-5-bromouracil
Homo sapiens;
-
IC50: 0.041 mM
0.026
6-[(4'-aminoimidazol-1'-yl)methyl]-5-chlorouracil
Homo sapiens;
-
IC50: 0.026 mM
0.143
6-[(4'-aminoimidazol-1'-yl)methyl]uracil
Homo sapiens;
-
IC50: 0.143 mM
0.5
6-[(4'-nitroimidazol-1'-yl)methyl]uracil
Homo sapiens;
-
IC50: 0.5 mM
0.1
7-(methylsulfanyl)-2-phenyl[1,2,4]triazolo[1,5-a][1,3,5]triazin-5(4H)-one
Homo sapiens;
-
IC50 above 0.1 mM, pH and temperature not specified in the publication
0.04263 - 0.045
7-deazaxanthine
0.351
KIN56
Homo sapiens;
-
IC50: 0.351 mM
0.077
NSC 65043
Homo sapiens;
-
IC50: 0.077 mM
0.0017 - 0.027
[8-(2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-1-yl)octyl]phosphonic acid
0.0073 - 0.0151
[8-(2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimidin-1-yl)octyl]phosphonic acid
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00386
-
in normal uterine cervix tissue
0.00527
-
mean thymidine phosphorylase activity in population
0.01
-
mitochondrial neurogastrointestinal encephalomyopathy syndrome patient, leukocytes
0.04176
-
in cancerous uterine cervix tissue
0.2 - 0.32
-
leukocytes of heterozygous individuals in enzyme mutation and mitochondrial neurogastrointestinal encephalomyopathy syndrome
0.24
-
crude extract, at pH 7.5 at 37°C
0.36 - 0.8
-
wild-type activity in leukocytes
4.3
-
after 17.9fold purification, at pH 7.5 at 37°C
1100
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5
-
thymine production, assay at
7.4
-
assay at
7.6
-
assay at
7.8
-
assay at
10
-
assay at, pH 10 is used because 2-deoxy-D-ribose 1-phosphate is heat labile at pH 7.4
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
thymidine phosphorylase mRNA levels are low and statistically not different in whole basal cell carcinoma cells and normal skin and are strongly downregulated in laser capture microdissected-basal cell carcinoma cells as compared with laser capture microdissected-normal epidermis
Manually annotated by BRENDA team
-
higher PyNpase levels in tumor tissue than in normal tissue or tissue adjacent to the tumor, PyNpase levels independent of age, gender, history of recurrence, multiplicity, tumor size, tumor shape, pathological stage (Ta, T1-4), PyNpase levels differ between histological stages being highest in G3, and between papillary versus non-papillary growth pattern, higher PyPnase levels in high-risk group (G3 or Tis or T2) than in low-risk group (primary, single, G1 and Ta)
Manually annotated by BRENDA team
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presurgery serum from 47 patients with ovarian cancer, and control serum from women with normal ovaries, treated surgically due to nononcological reasons. Significant higher enzyme activity in malignant serum specimen from ovarian cancer patients when compared to the control
Manually annotated by BRENDA team
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thymidine phosphorylase shows a characteristic pattern of distribution dependent on the phase of the menstrual cycle: enzyme expression moves from stroma to epithelium as the cycle progresses34 and is inversely correlated with estradiol concentrations
Manually annotated by BRENDA team
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patients with PD-ECGF/TP-positive tumors have a poorer prognosis than those with negative tumors
Manually annotated by BRENDA team
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high expression
Manually annotated by BRENDA team
-
epidermoid
Manually annotated by BRENDA team
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cholangiocarcinoma-derived cell line, which has a naturally high level of endogenous thymidine phosphorylase
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
from peripheral blood
Manually annotated by BRENDA team
-
the cytoplasmic level of heterogeneous nuclear ribonucleoprotein K is significantly correlated with the elevated expression of thymidine phosphorylase, and high levels of both proteins are predictive of a poor prognosis in nasopharyngeal carcinoma
Manually annotated by BRENDA team
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the enzyme is strongly induced in the serum-deprived nasopharyngeal carcinoma cells, the serum deprivation-triggered upregulation of the enzyme is due to mRNA stabilization, not protein stabilization or transcriptional activation requiring the mRNA CU-rich element sequence and heterogeneous nuclear ribonucleoprotein K, overview
Manually annotated by BRENDA team
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the enzyme is strongly induced in the serum-deprived nasopharyngeal carcinoma cells, the serum deprivation-triggered upregulation of the enzyme is due to mRNA stabilization, not protein stabilization or transcriptional activation requiring the mRNA CU-rich element sequence and heterogeneous nuclear ribonucleoprotein K, overview
Manually annotated by BRENDA team
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malignant tissue
Manually annotated by BRENDA team
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tissue from 47 patiens with ovarian cancer after surgery. Significant higher enzyme activity in malignant tissue from ovarian cancer patients when compared to the control
Manually annotated by BRENDA team
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tissue from 47 patiens with ovarian cancer after surgery. Significant higher enzyme activity in malignant tissue from ovarian cancer patients when compared to the control
Manually annotated by BRENDA team
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shows significantly greater activity in cancer tissues than in normal tissues
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
neutrophil in gastric cancer tissue
Manually annotated by BRENDA team
additional information
-
the mechanism behind the secretion of thymidine phosphorylase is possibly a posttranslational process whereby serine residues of the enzyme are covalently linked to phosphate groups of nucleotides, leading to the formation of a nucleotidylated protein that can be secreted
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Manually annotated by BRENDA team
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
48855
-
2 * 48855, mass spectrometry
49024
-
2 * 49024, calculated from amino acid sequence
50000
-
2 * 50000, SDS-PAGE
52000
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recombinant enzyme lacking 10 amino acid residues, SDS-PAGE
58000
-
2 * 58000, SDS-PAGE, enzyme is capable of being converted to a less active form larger in MW and possibly trimeric or tetrameric in structure
60000
-
2 * 60000, SDS-PAGE
90000
-
-
110000
120000
-
gel filtration
121000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
-
two alternative enzyme forms, a 27 kDa splice variant and another form containing five additional amino acids on the N-terminus, the second form is processed at Thr6 instead of Ala11
additional information
-
the mechanism behind the secretion of thymidine phosphorylase is possibly a posttranslational process whereby serine residues of the enzyme are covalently linked to phosphate groups of nucleotides, leading to the formation of a nucleotidylated protein that can be secreted
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme complexed with TPI
-
purified recombinant thymidine phosphorylase, free and in complex with 5-iodouracil, X-ray diffraction structure determination and analysis at 3.0 A and 2.5 A resolutions, respectively
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structure of enzyme from crystals grown in the presence of thymidine
-
structure of HTP bound to the small molecule inhibitor 5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracil hydrochloride, glutathione S-transferase fused to thymidine phosphorylase residues 12–482 (based on Swissprot accession number P19971) via a thrombin-cleavable linker, crystallizationd at 15°C using the hanging-drop vapor method
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X-ray diffraction structure determination and analysis of the free enzyme at 3.5 A resolution, and of the in complex with the small and potent inhibitor 5-chloro-6-[1-(2-iminopyrrolidinyl)methyl] uracil at 2.1 A resolution
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
65
-
30 min, complete inactivation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
stable to repeated freezing and thawing
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, phosphate buffer containing 2% mannitol, stable for over 1 year, human enzyme
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4°C, storage results in a decrease of the 120 kDA component, an increase of the high molecular weight component, and a loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
98% purity
-
ammonium sulfate fractionation
-
chromatography
-
homogeneity
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Ni+-chelation-affinity chromatography
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Q-Sepharose column chromatography and phenyl Sepharose column chromatography
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recombinant enzyme from Escherichia coli strain BL21(DE3) by calmodulin affinity chromatography, cleavage of the calmodulin binding protein tag by enterokinase, removal by chromatography on soybean trypsin inhibitor-sepharose
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recombinant wild-type and mutan enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
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separation of uridine phosphorylase and thymidine phosphorylase activities
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Chinese hamster V-79 cells
-
expressed in CHO cells
-
expressed in Colo-320TP1 and C26A cells
-
expressed in Escherichia coli
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expressed in Escherichia coli Rosetta (DE3) cells
-
expressed in Jurkat cells
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expressed in V-79 hamster cells
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expressed in V79 Chinese hamster cells
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expression in KB cells
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expression in rat vascular smooth muscle cell
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expression of the calmodulin binding protein-tagged enzyme in Escherichia coli strain BL21(DE3) cells transformed with the pCal-n-EK/TP and pGroESL vectors
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expression of wild-type and mutan enzymes in Escherichia coli strain BL21(DE3)
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recombinant enzyme lacks 10 amino acids at amino-terminus
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transfected into colon cancer cell line Colo320
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
capecitabine does not affect enzyme activity and expression
-
chorionic gonadotropin36 and a combination of progesterone and transforming growth factor b1 upregulate the enzyme expression. The enzyme is also upregulated in several diseases, detailed overview
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the enzyme expression is is inversely correlated with estradiol concentrations in the endometrium
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the enzyme is strongly induced in the serum-deprived nasopharyngeal carcinoma cell lines TW-01, TW-02, and TW-04, the serum deprivation-triggered upregulation of the enzyme is due to mRNA stabilization, not protein stabilization or transcriptional activation requiring the mRNA CU-rich element sequence and heterogeneous nuclear ribonucleoprotein K, mechanism and kinetics, overview
-
treatment with 0.005-0.04 mM tamoxifen decreases mRNA and protein levels through AKT inactivation
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H116F
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site-directed mutagenesis, inactive mutant
H116K
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site-directed mutagenesis, inactive mutant
I214A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
K115A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R202E
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site-directed mutagenesis, inactive mutant
S217G
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site-directed mutagenesis, inactive mutant
Y199A
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site-directed mutagenesis, inactive mutant
Y199F
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Y199L
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
methods to measure thymidine and deoxyuridine concentrations and thymidine phosphorylase activity in biological samples. Thymidine phosphorylase activity can be measured by an endpoint determination of the thymine formed after 1 h incubation of the buffy coat homogenate in the presence of a large excess of its substrate thymidine, either spectrophotometrically or by HPLC-UV. The protocols allow the detection of thymidine phosphorylase dysfunction in patients with mitochondrial neurogastrointestinal encephalomyopathy, MNGIE
medicine