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Information on EC 2.4.2.3 - uridine phosphorylase
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2.4.2.3 uridine phosphorylaseIUBMB Comments
The enzyme participates the the pathways of pyrimidine ribonucleosides degradation and salvage. The mammalian enzyme also accepts 2'-deoxyuridine.
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Word Map
- 2.4.2.3
- pyrimidine
- nucleoside
- thymidine
- uracil
- 5-fluorouracil
-
phosphorolysis
-
salvage
-
phosphoribosyltransferase
- phosphorylases
- orotate
-
fluoropyrimidine
- udp
- cytidine
- thymidylate
- 5'-deoxy-5-fluorouridine
- 5-fluoro-2'-deoxyuridine
- dihydropyrimidine
- 5-fluorouridine
- acyclonucleoside
- ribose-1-phosphate
-
mete
- 5-methyluridine
- orotidine
-
uridine-cytidine
- capecitabine
- dthdpase
- dihydrouracil
-
fdurd
- diagnostics
- medicine
- synthesis
- drug development
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
apUP, L-UrdPase, More, PcUP1, PcUP2, phosphorylase, uridine, pynpase, pyrimidine nucleoside phosphorylase, pyrimidine phosphorylase, pyrimidine/purine nucleoside phosphorylase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
apUP
PcUP1
PcUP2
phosphorylase, uridine
-
-
-
-
pynpase
pyrimidine nucleoside phosphorylase
pyrimidine phosphorylase
-
-
-
-
udp
UDRPase
-
-
-
-
UP1
UP2
UPase
UPase-2
UPH
UrdPase
-
-
-
-
uridine phosphorylase
uridine phosphorylase-1
uridine phosphorylase-2
uridine:orthophosphate alpha-D-ribosyltransferase
-
-
-
-
additional information
the enzyme belongs to the NP1 subfamily of the nucleoside phosphorylase, NP, superfamily of enzymes
UPase
-
-
-
-
UPH
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
sequential mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
sequential mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
sequential mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
rapid-equilibrium random mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
ordered bi-bi mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
ordered bi-bi mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
random mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
phosphate binds before uridine and ribose 1-phosphate is released after uracil
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
sequential rather than ping-pong mechanism, addition of substrate is random
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
ordered bi-bi mechanism, phosphate binds before uridine and alpha-D-ribose 1-phosphate is released after uracil
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
binding isotope effects indicate ground-state stabilization in the Michaelis complex, such as bonding environment, ribosyl pucker, and natural bond orbital charges
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
steady-state random kinetic mechanism. Reaction follows an ANDN/SN2 mechanism where chemistry contributes significantly to the overall rate-limiting step of the reaction. No kinetically significant proton transfer step is involved at the transition state. Proton transfer to neutralize the leaving group is not part of transition state formation, consistent with an enzyme-stabilized anionic uracil as the leaving group. Kinetic analysis as a function of pH indicates one protonated group essential for catalysis and for substrate binding
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
mutational analysis supports for the push-pull model of catalysis, proposed catalytic mechanism of PcUP1, modeling, overview. Deprotonation of phosphate by Arg104, increases the negative charge on the phosphate oxygen, leading to repulsion between the electrons of phosphate oxygen and electron pairs of the endocylic ribosyl oxygen and the formation of an intermediate oxocarbenium ion. At the same time, the Gln206, Arg208 and Arg264-N1 hydrogen network-bond pulls electrons from the glycosidic bond onto the pyrimidine ring. These two actions work in concert to weaken the glycosidic bond. Arg39 pivots, to physically push the phosphate closer to the ribose moiety. After glycosidic bond cleavage, ribose-1-phosphate dissociates from the active pocket, and then an active water reprotonates the negatively charged purine. The final step is to release the neutral purine base
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
rapid-equilibrium random mechanism
Escherichia coli B / ATCC 11303
-
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
mutational analysis supports for the push-pull model of catalysis, proposed catalytic mechanism of PcUP1, modeling, overview. Deprotonation of phosphate by Arg104, increases the negative charge on the phosphate oxygen, leading to repulsion between the electrons of phosphate oxygen and electron pairs of the endocylic ribosyl oxygen and the formation of an intermediate oxocarbenium ion. At the same time, the Gln206, Arg208 and Arg264-N1 hydrogen network-bond pulls electrons from the glycosidic bond onto the pyrimidine ring. These two actions work in concert to weaken the glycosidic bond. Arg39 pivots, to physically push the phosphate closer to the ribose moiety. After glycosidic bond cleavage, ribose-1-phosphate dissociates from the active pocket, and then an active water reprotonates the negatively charged purine. The final step is to release the neutral purine base
-
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pentosyl group transfer
pentosyl group transfer
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
uridine:phosphate alpha-D-ribosyltransferase
The enzyme participates the the pathways of pyrimidine ribonucleosides degradation and salvage. The mammalian enzyme also accepts 2'-deoxyuridine.
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CAS REGISTRY NUMBER
COMMENTARY
9030-22-2
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5'-deoxy-5-fluorouridine + alpha-D-ribose 1-phosphate
5'-deoxy-5-fluorouridine + phosphate
-
-
-
-
?
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxy-alpha-D-ribose 1-phosphate
-
-
-
?
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxy-D-ribose-1-phosphate
-
-
also accepts 2'-deoxypyrimidine nucleosides in higher organisms
-
r
5-fluorouracil + alpha-D-ribose 1-phosphate
5-fluorouridine + phosphate
-
-
-
-
?
5-methyluridine + phosphate
thymine + alpha-D-ribose 1-phosphate
-
19% of the activity with uridine
-
-
?
6-methyluracil + 2-deoxy-D-ribose 1-phosphate
6-methyl-2'-deoxyuridine + phosphate
-
VchUPh shows selectivity toward 6-methyluracil acting as a pseudosubstrate. Repulsion between the hydrophilic hydroxyl group of the active-site residue Thr93 of VchUPh and the hydrophobic methyl group of 6-methyluracil prevents the oxygen atom O4' of the ribose moiety and the phosphate oxygen atom O3P of ribose 1-phosphate from forming hydrogen bonds with OG1_Thr93, which are essential for the enzymatic reaction. This, apparently, renders VchUPh inactive in the enzymatic synthesis of 6-methyluridine from 6-methyluracil
-
-
ir
6-methyluracil + alpha-D-ribose 1-phosphate
6-methyluridine + phosphate
-
VchUPh shows selectivity toward 6-methyluracil acting as a pseudosubstrate. Repulsion between the hydrophilic hydroxyl group of the active-site residue Thr93 of VchUPh and the hydrophobic methyl group of 6-methyluracil prevents the oxygen atom O4' of the ribose moiety and the phosphate oxygen atom O3P of ribose 1-phosphate from forming hydrogen bonds with OG1_Thr93, which are essential for the enzymatic reaction. This, apparently, renders VchUPh inactive in the enzymatic synthesis of 6-methyluridine from 6-methyluracil
-
-
ir
6-methyluridine + phosphate
6-methyluracil + alpha-D-ribose 1-phosphate
-
-
-
?
arabinofuranosyl-5-ethyluracil + phosphate
5-ethyluracil + arabinose-1-phosphate
-
weak substrate
-
-
?
cytidine + phosphate
cytosine + alpha-D-ribose 1-phosphate
-
-
-
-
?
guanosine + phosphate
guanine + alpha-D-ribose 1-phosphate
10% of the activity with uridine
-
-
r
inosine + phosphate
hypoxanthine + alpha-D-ribose 1-phosphate
-
-
-
?
pyrimidine nucleoside + phosphate
pyrimidine base + alpha-D-ribose 1-phosphate
-
most pyrimidine nucleosides except for 4-amino-substituted species like deoxycytidine
or alpha-D-deoxyribose 1-phosphate
-
r
2'-deoxyuridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
?
2'-deoxyuridine + phosphate
uracil + alpha-D-ribose 1-phosphate
Shewanella oneidensis MR-1 / ATCC 700550
-
-
-
?
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
-
6% of the activity with uridine
-
?
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
-
activities of uridine, deoxyuridine and thymidine phosphorylase from Giardia lamblia remain associated throughout purification suggesting that a single enzyme is responsible for the 3 activities
-
-
?
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
-
12% of the activity with uridine
-
-
?
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
-
18% of the activity with uridine
-
-
?
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
-
catalyzed by a different protein or by a different active center of the same enzyme
-
r
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
-
unlike cytosolic enzyme, enzyme from plasma membranes shows little or no deoxyuridine-cleaving activity
-
-
?
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
-
-
-
-
?
5'-deoxy-5-fluorouridine + phosphate
5-fluorouracil + 5-deoxyribose-1-phosphate
-
-
-
-
?
5'-deoxy-5-fluorouridine + phosphate
5-fluorouracil + 5-deoxyribose-1-phosphate
-
25% of the activity with uridine
-
-
?
5-bromo-2'-deoxyuridine + phosphate
5-bromouracil + 2-deoxribose 1-phosphate
-
27% of the activity with uridine
-
-
?
5-bromo-2'-deoxyuridine + phosphate
5-bromouracil + 2-deoxribose 1-phosphate
-
75% of the activity with uridine
-
-
?
5-bromouracil + deoxyribose 1-phosphate
5-bromodeoxyuridine + phosphate
-
-
-
-
?
5-bromouracil + deoxyribose 1-phosphate
5-bromodeoxyuridine + phosphate
-
-
-
-
?
5-bromouridine + phosphate
5-bromouracil + alpha-D-ribose 1-phosphate
-
69% of the activity with uridine
-
-
?
5-bromouridine + phosphate
5-bromouracil + alpha-D-ribose 1-phosphate
-
40% of the activity with uridine
-
-
?
5-bromouridine + phosphate
5-bromouracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxyribose-1-phosphate
-
14% of the activity with uridine
-
-
?
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxyribose-1-phosphate
-
15% of the activity with uridine
-
-
?
5-fluorouracil + alpha-D-ribose-1-phosphate
5-fluorouridine + phosphate
-
-
-
-
?
5-fluorouracil + alpha-D-ribose-1-phosphate
5-fluorouridine + phosphate
-
-
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + alpha-D-ribose 1-phosphate
-
-
-
-
r
5-fluorouridine + phosphate
5-fluorouracil + alpha-D-ribose-1-phosphate
-
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + alpha-D-ribose-1-phosphate
-
15% of the activity with uridine
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + alpha-D-ribose-1-phosphate
-
85% of the activity with uridine
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + alpha-D-ribose-1-phosphate
-
-
-
-
?
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
92% compared to the activity with uridine
-
-
?
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
92% compared to the activity with uridine
-
-
?
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
-
27% of the activity with uridine
-
-
?
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
-
-
-
?
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
Shewanella oneidensis MR-1 / ATCC 700550
-
-
-
?
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
-
-
-
-
r
deoxyuridine + phosphate
uracil + 2-deoxy-alpha-D-ribose 1-phosphate
-
-
-
?
deoxyuridine + phosphate
uracil + 2-deoxy-alpha-D-ribose 1-phosphate
14% of the activity with uridine
-
-
r
deoxyuridine + phosphate
uracil + deoxy-D-ribose 1-phosphate
66% compared to the activity with uridine
-
-
?
deoxyuridine + phosphate
uracil + deoxy-D-ribose 1-phosphate
66% compared to the activity with uridine
-
-
?
fluorouridine + phosphate
fluorouracil + alpha-D-ribose-1-phosphate
-
-
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
60% compared to the activity with uridine
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
60% compared to the activity with uridine
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
-
2% of the activity with uridine
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
-
the activities of uridine, deoxyuridine and thymidine phosphorylases from Giardia lamblia remain associated throughout purification, suggesting that a single enzyme is responsible for the 3 activities
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
-
21% of the activity with uridine
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
-
to a lesser extent compared to uridine
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
-
22% of the activity with uridine
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
-
-
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
-
to a lesser extent compared to uridine
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
-
-
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
-
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
-
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
Shewanella oneidensis MR-1 / ATCC 700550
-
-
-
?
uracil + alpha-D-ribose 1-phosphate
uridine + phosphate
-
uridine prevents the glucose deprivation-induced death of immunostimulated astrocytes via the action of uridine phosphorylase
-
-
?
uracil arabinoside + phosphate
uracil + arabinose-1-phosphate
-
10% of the activity with uridine
-
-
?
uracil arabinoside + phosphate
uracil + arabinose-1-phosphate
-
10% of the activity with uridine
-
-
?
uracil arabinoside + phosphate
uracil + arabinose-1-phosphate
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
the optimal substrate for the enzyme is uridine. It shows no activity for 5-fluorouridine, cytidine, or 2-deoxycytidine
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
the optimal substrate for the enzyme is uridine. It shows no activity for 5-fluorouridine, cytidine, or 2-deoxycytidine
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
key enzyme in pyrimidine-salvage pathway
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
liver enzyme is highly specific to uridine
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
equilibrium position favouring nucleoside synthesis
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
broader specificity than human enzyme
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
enzyme of pyrimidine salvage pathway
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
in conjunction with uridine kinase, the enzyme provides a route for the conversion of uracil to UMP via uridine
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
role in degradation of pyrimidine nucleosides as well as in the salvage pathway for nucleic acid synthesis
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
cleavage of the N-glycosidic bond
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
enzyme of pyrimidine salvage pathway
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
Shewanella oneidensis MR-1 / ATCC 700550
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
best substrate, active site structure, overview
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
?
additional information
?
-
-
no substrates are: thymidine, deoxyuridine, fluorodeoxyuridiune, 5'-deoxyfluorouridine
-
-
?
additional information
?
-
-
no substrate: 5-substituted-2,2'-anhydrouridine
-
-
?
additional information
?
-
-
catalyzes the first step of uridine degradation to beta-alanine in liver
-
-
?
additional information
?
-
UPP catalyzes the reversible phosphorolysis of uracil ribosides and analogous compounds to their respective nucleobases and ribose-1-phosphate, structural mechanisms, overview
-
-
?
additional information
?
-
-
UPP catalyzes the reversible phosphorolysis of uracil ribosides and analogous compounds to their respective nucleobases and ribose-1-phosphate, structural mechanisms, overview
-
-
?
additional information
?
-
-
no substrates: 2-deoxyuridine, adenosine
-
-
?
additional information
?
-
-
no substrate: 5-substituted-2,2'-anhydrouridine
-
-
?
additional information
?
-
-
the enzyme is regulated by multiple lipid-sensing nuclear receptors, gene expression is diurnally regulated
-
-
?
additional information
?
-
-
no substrates: 3'-azido-2',3'-dideoxy-5-methyluridine, 3'-azido-2',3'-dideoxy-5-ethyluridine, 2',3'-dideoxy-5-ethyluridine, 3'-chloro-2',3'-dideoxy-5-ethyluridine, 3'-chloro-2',3'-dideoxy-5-methyluridine, 3'-bromo-2',3'-dideoxy-5-ethyluridine, 2'-deoxylyxofuranosyl-5-ethyluracil, 3'-O-acetyl-2,2'-anhydro-5-ethyluridine, 2,3'-anhydro-2'-deoxy-5-ethyluridine, 2,5'-anhydro-2'-deoxy-5-ethyluridine
-
-
?
additional information
?
-
-
catalyzes the first step of uridine degradation to beta-alanine in liver
-
-
?
additional information
?
-
-
no substrates: inosine, adenosine, guanosine, thymidine
-
-
?
additional information
?
-
-
the enzyme also activates pyrimidine-containing drugs, including 5-fluorouracil, mechanism of the enzyme-drug interaction, overview
-
-
?
additional information
?
-
-
no substrates: cytosine, deoxycytidine, orotidine
-
-
?
additional information
?
-
strict substrate specificty of the enzyme, overview. Deoxyadenosine, and deoxyguanosine are poor substrates, thymidine, cytidine, deoxycytidine, inosine, and adenosine are no substrates
-
-
?
additional information
?
-
-
strict substrate specificty of the enzyme, overview. Deoxyadenosine, and deoxyguanosine are poor substrates, thymidine, cytidine, deoxycytidine, inosine, and adenosine are no substrates
-
-
?
additional information
?
-
-
substrate specificity, and substrate binding structures, detailed overview
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
-
-
-
-
r
pyrimidine nucleoside + phosphate
pyrimidine base + alpha-D-ribose 1-phosphate
-
most pyrimidine nucleosides except for 4-amino-substituted species like deoxycytidine
or alpha-D-deoxyribose 1-phosphate
-
r
uracil + alpha-D-ribose 1-phosphate
uridine + phosphate
-
uridine prevents the glucose deprivation-induced death of immunostimulated astrocytes via the action of uridine phosphorylase
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
key enzyme in pyrimidine-salvage pathway
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
enzyme of pyrimidine salvage pathway
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
in conjunction with uridine kinase, the enzyme provides a route for the conversion of uracil to UMP via uridine
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
role in degradation of pyrimidine nucleosides as well as in the salvage pathway for nucleic acid synthesis
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
enzyme of pyrimidine salvage pathway
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
Shewanella oneidensis MR-1 / ATCC 700550
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
-
-
-
?
additional information
?
-
-
catalyzes the first step of uridine degradation to beta-alanine in liver
-
-
?
additional information
?
-
UPP catalyzes the reversible phosphorolysis of uracil ribosides and analogous compounds to their respective nucleobases and ribose-1-phosphate, structural mechanisms, overview
-
-
?
additional information
?
-
-
UPP catalyzes the reversible phosphorolysis of uracil ribosides and analogous compounds to their respective nucleobases and ribose-1-phosphate, structural mechanisms, overview
-
-
?
additional information
?
-
-
the enzyme is regulated by multiple lipid-sensing nuclear receptors, gene expression is diurnally regulated
-
-
?
additional information
?
-
-
catalyzes the first step of uridine degradation to beta-alanine in liver
-
-
?
additional information
?
-
-
the enzyme also activates pyrimidine-containing drugs, including 5-fluorouracil, mechanism of the enzyme-drug interaction, overview
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
stabilizes the enzyme, which possesses an intermolecular metal-binding site, structure, overview
additional information
additional information
enzyme UP1 has a potential metal binding site but contains no metal ions
additional information
enzyme UP1 has a potential metal binding site but contains no metal ions
additional information
-
enzyme UP1 has a potential metal binding site but contains no metal ions
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-((2-pyrrolidine-1-yl)ethyl)uracil
inhibits both enzymic activity and growth of Plasmodium falciparum
1-(1',2'-dihydroxypropyl)-5,6-tetramethyleneuracil
-
only the R-enantiomer inhibits, but not the S-enantiomer
1-(1',3'-dihydroxy-2'-propoxy)methyl-5,6-tetramethyleneuracil
-
inhibits forward and reverse reaction
1-(1',3'-dihydroxy-2'-propoxy)methyl-5-benzyluracil
-
i.e. DHPBU, competitive
3-((2-pyrrolidine-1-yl)ethyl)uracil
inhibits both enzymic activity and growth of Plasmodium falciparum
4-benzyl-6-hydroxy-2-oxo-1,2-dihydropyridine-3-carbonitrile
2% inhibition at 0.001 mM
4-ethyl-6-hydroxy-2-oxo-1,2-dihydropyridine-3-carbonitrile
25% inhibition at 0.001 mM
4-hydroxy-5-[[(2-hydroxyethyl)amino]methyl]-3,4-dihydropyrimidin-2(1H)-one
2% inhibition at 0.001 mM
5-Azauracil
-
reaction is inhibited in the direction of deoxyuridine synthesis more than in the direction of their cleavage at the same concentration of 5-azauracil
5-benzyl-1-(2'-hydroxyethoxymethyl)uracil
competitive inhibition with respect to uridine, noncompetitive inhibition with respect to phosphate
5-benzyl-6-hydroxy-4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile
43% inhibition at 0.001 mM
5-[(diethylamino)methyl]-6-hydroxy-4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile
25% inhibition at 0.001 mM
5-[(dimethylamino)methyl]-6-hydroxy-4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile
81% inhibition at 0.001 mM
5-[[(1,3-dihydroxypropan-2-yl)amino]methyl]-6-hydroxy-4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile
82% inhibition at 0.001 mM
5-[[(2,3-dihydroxypropyl)amino]methyl]-6-hydroxy-4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile
78% inhibition at 0.001 mM
6-hydroxy-2-oxo-1,2-dihydropyridine-3-carbonitrile
67% inhibition at 0.001 mM
6-hydroxy-2-oxo-4-(propan-2-yl)-1,2-dihydropyridine-3-carbonitrile
31% inhibition at 0.001 mM
6-hydroxy-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile
42% inhibition at 0.001 mM
6-hydroxy-2-oxo-4-propyl-1,2-dihydropyridine-3-carbonitrile
16% inhibition at 0.001 mM
6-hydroxy-4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile
70% inhibition at 0.001 mM
6-hydroxy-4-methyl-2-oxo-5-phenyl-1,2-dihydropyridine-3-carbonitrile
12% inhibition at 0.001 mM
6-hydroxy-4-methyl-2-oxo-5-[(piperidin-1-yl)methyl]-1,2-dihydropyridine-3-carbonitrile
49% inhibition at 0.001 mM
6-hydroxy-4-methyl-5-[(morpholin-4-yl)methyl]-2-oxo-1,2-dihydropyridine-3-carbonitrile
51% inhibition at 0.001 mM
6-hydroxy-4-propyl-1H-pyridin-2-one-3-carbonitrile
16% inhibition at 0.001 mM
6-hydroxy-5-(((2-hydroxyethyl) amino) methyl)-4-methyl-1H-pyridin-2-one-3-carbonitrile
-
6-hydroxy-5-(((2-hydroxyethyl)amino)methyl)-4-methyl-1H-pyridin-2-one-3-carbonitrile
80% inhibition at 0.001 mM
Acyclonucleoside analogues
-
consisting of 5- and 5,6-substituted uracils and different acyclic chains
-
Deoxyglucosylthymine
-
phosphorolysis of uridine and deoxyuridine, synthesis of uridine at concentrations of 0.10 mM, 0.018 mM and 0.14 mM, not: phosphorolysis of deoxyuridine or thymidine at 0.19 mM
guanidine hydrochloride
-
50% loss of activity at 1.04 M, only little residual activity between 2 and 6 M
potassium 5-cyano-4-methyl-6-oxo-1,6-dihydropyridin-2-olate
60% inhibition at 0.001 mM
2,2'-anhydrouridine
-
high-resolution three-dimensional structure of uridine phosphorylase from in complex with the competitive inhibitor determined by X-ray diffraction (PDB ID 6RCA), detailed binding structure analysis, overview. The binding of the inhibitor at the active site of the protein is energetically more favorable than the binding of the native substrate uridine. The inhibitor molecules are located in all six active sites of the hexameric UPh molecule. Effect of 2,2'-anhydrouridine binding on the conformation of structurally functional elements of VchUPh
5-benzylacyclouridine
-
0.01 mM, 90% inhibition of normal tissues, 40-60% inhibition of carcinoma tissue
5-benzylacyclouridine
an UPP1-specific inhibitor. Binding of the inhibitor to the UPP1 active site, structure, overview
6-Methyluracil
-
acts as a pseudosubstrate, molecular docking into the active site, molecular-dynamics simulations of the complex. Repulsion between the hydrophilic hydroxyl group of the active-site residue Thr93 of VchUPh and the hydrophobic methyl group of 6-methyluracil prevents the oxygen atom O4' of the ribose moiety and the phosphate oxygen atom O3P of ribose 1-phosphate from forming hydrogen bonds with OG1_Thr93, which are essential for the enzymatic reaction. This, apparently, renders VchUPh inactive in the enzymatic synthesis of 6-methyluridine from 6-methyluracil
alpha-D-ribose 1-phosphate
product inhibition pattern, noncompetitive versus uridine, competitive versus phosphate, overview
alpha-D-ribose 1-phosphate
-
product inhibition, noncompetitive with respect to uridine and phosphate
Uracil
product inhibition pattern, noncompetitive versus uridine and phosphate, overview
Uracil
-
product inhibition, oncompetitive with respect to uridine and phosphate
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
UPase expression is up-regulated by glucose deprivation in mRNA as well as protein levels
-
additional information
-
UPase expression is up-regulated by glucose deprivation in mRNA as well as protein levels
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.121
2'-deoxyuridine
in 50 mM potassium phosphate buffer, pH 7.5, 25°C
0.036
5-fluorouracil
-
cosubstrate: alpha-D-ribose-1-phosphate, enzyme from liver
0.046
5-fluorouracil
-
cosubstrate: alpha-D-ribose-1-phosphate, enzyme from colon tumor
0.06
5-fluorouracil
-
cosubstrate: alpha-D-ribose-1-phosphate, enzyme from colon tumor
0.065
5-methyluridine
in 50 mM potassium phosphate buffer, pH 7.5, 25°C
0.02
alpha-D-ribose-1-phosphate
-
cosubstrate: 5-fluorouracil, enzyme from liver
0.038
alpha-D-ribose-1-phosphate
-
cosubstrate: 5-fluorouracil, enzyme from colon tumor
0.04
alpha-D-ribose-1-phosphate
-
cosubstrate: 5-fluorouracil, enzyme from colon tumor
0.087
alpha-D-ribose-1-phosphate
-
cosubstrate: uracil, enzyme from colon tumor
0.0489
thymidine
pH and temperature not specified in the publication
0.215
thymidine
in 50 mM potassium phosphate buffer, pH 7.5, 25°C
0.367
Uracil
-
cosubstrate: alpha-D-ribose-1-phosphate, enzyme from colon tumor
6.96
uridine
pH and temperature not specified in the publication
7.55
uridine
pH and temperature not specified in the publication
additional information
additional information
Michaelis-Menten kinetics and Lineweaver-Burk plots
-
additional information
additional information
kinetic analysis of UP1 is not consistent with a strong effect of substrate cooperativity
-
additional information
additional information
kinetic analysis of UP1 is not consistent with a strong effect of substrate cooperativity
-
additional information
additional information
-
kinetic analysis of UP1 is not consistent with a strong effect of substrate cooperativity
-
additional information
additional information
kinetic analysis of UP2 is not consistent with a strong effect of substrate cooperativity
-
additional information
additional information
kinetic analysis of UP2 is not consistent with a strong effect of substrate cooperativity
-
additional information
additional information
-
kinetic analysis of UP2 is not consistent with a strong effect of substrate cooperativity
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.41
thymidine
pH and temperature not specified in the publication
982
uridine
pH and temperature not specified in the publication
1188
uridine
pH and temperature not specified in the publication
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
8.38
thymidine
pH and temperature not specified in the publication
141.1
uridine
pH and temperature not specified in the publication
157.4
uridine
pH and temperature not specified in the publication
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000018
5-(3'-Benzyloxybenzyl)-1-[(1'-aminomethyl-2'-hydroxyethoxy)methyl]uracil
-
-
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
pH dependence of enzyme activities with different substrates, overview
additional information
-
pH dependence of enzyme activities with different substrates, overview
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5
7.4
7.5
8.2
8.5
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.8 - 9
-
pH 5.8: about 50% of activity maximum, pH 9.0: about 40% of activity maximum
6 - 8.5
pH dependence of enzyme activities with different substrates, overview
6.5 - 10.5
-
pH 6.5: about 50% of activity maximum, pH 10.5: about 65% of activity maximum
7 - 7.75
-
pH 6.5: about 70% of activity maximum, pH 8.5: about 25% of activity maximum
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40 - 80
-
40°C: about 40% of activity maximum, 80°C: about 10% of activity maximum
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
-
-
-
brenda
-
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
colon 26 tumor cells transplanted in BALB/c mice
brenda
UPP1 is significantly upregulated in glioma, especially in glioblastoma
brenda
UPP1 is significantly upregulated in glioma, especially in glioblastoma
brenda
UPP1 expression is significantly downregulated in thyroid cancer
brenda
-
N-butyl-N-(4-hydoxybutyl) nitrosamine (BBN) treatment for 12 weeks induces invasive cancer development in mice
brenda
-
N-butyl-N-(4-hydoxybutyl) nitrosamine (BBN) treatment for 12 weeks induces superficial cancer development in rats
brenda
-
12, 16 and 20 weeks after initiation of BBN treatment: higher PyNpase level in invasive carcinoma and hyperplasia compared to controls
brenda
-
12 weeks after initiation of BBN treatment: higher PyNpase level in superficial cancer and hyperplasia compared to controls, 16 and 20 weeks after initiation of BBN treatment: higher PyNpase level in superficial cancer but not in hyperplasia compared to controls
brenda
-
negative correlation between UPase expression and the clinical outcome of breast cancer
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
associated with intermediate filament vimentin in fibroblasts and colon 26 cells
brenda
-
60-70% of the enzyme exists in the cytosol as a soluble protein
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
significant upregulation of UPP1 in thyroid cancer tissues compared with normal thyroid tissues is significantly correlated with lymph node metastasis, tumour stage and tumour size. In the cell, reduced UPP1 expression significantly suppresses the migration, invasion and proliferation. Downregulation of UPP1 gene expression in TPC and BCPAP cells inhibits invasion and induces apoptosis in the thyroid cancer cells. Impact of UPP1 silencing on 5-fluorouracil (5-FU) chemo sensitivity in thyroid cancer cell lines
metabolism
physiological function
additional information
evolution
phylogenetic analysis of UPs in oomycetes
metabolism
uridine phosphorylase is a key enzyme in the pyrimidine salvage pathway, catalyzing the reversible phosphorolysis of uridine to uracil and ribose-1-phosphate
metabolism
uridine phosphorylase is a ubiquitous enzyme involved in pyrimidine salvage and maintenance of uridine homeostasis
metabolism
uridine phosphorylase (UP) is a key enzyme of pyrimidine salvage pathways that enables the recycling of endogenous or exogenous-supplied pyrimidines and plays an important intracellular metabolic role
metabolism
-
uridine phosphorylase (UP) is a key enzyme of pyrimidine salvage pathways that enables the recycling of endogenous or exogenous-supplied pyrimidines and plays an important intracellular metabolic role
-
physiological function
-
the enzyme contributes to the antineoplastic activity of 5'-deoxy-5-fluorouridine. The peroxisome proliferator-activated receptor gamma coactivator-1alpha enhances antiproliferative activity of 5-deoxy-5-fluorouridine in cancer cells through induction of uridine phosphorylase, overview
physiological function
uridine phosphorylase is a ubiquitous enzyme involved in pyrimidine salvage and maintenance of uridine homeostasis. UPP1 plays a role in the activation of pyrimidine nucleoside analogues used in chemotherapy, such as 5-fluorouracil and its prodrug, capecitabine
physiological function
enzyme UPP1 plays an essential role in pyrimidine salvage and regulation of uridine homeostasis. It plays a vital role in the stimulation of pyrimidine nucleoside analogues. UPP1 expression effects on 5-fluorouracil regulates epithelial-mesenchymal transition pathway. UPP1 acts as a crucial oncogene in thyroid cancer regulating epithelial-mesenchymal transition. Upregulation of UPP1 increases lymph node metastasis risk
physiological function
UPP1 interacts with immune checkpoint members in glioma
physiological function
-
uridine phosphorylase (UPh) is the enzyme that catalyzes the synthesis of thymidine or 5-methyluridine from thymine, as well as their phosphorolysis
additional information
-
bacterial thymidine phosphorylases of the NP-II family cannot bind 6-methyluracil in a proper conformation required for the catalysis because of a close contact between the 6-methyl group and Phe210. Structure-function analysis, overview
additional information
-
enzyme structure modeling, molecular dynamics simulation, overview. Calculation of the protein-ligand binding free energy
additional information
strict conservation of UP1 key residues in the binding pocket, structure analysis of PcUP1 with bound ligands, active site structure and substrate binding, overview
additional information
strict conservation of UP1 key residues in the binding pocket, structure analysis of PcUP1 with bound ligands, active site structure and substrate binding, overview
additional information
-
strict conservation of UP1 key residues in the binding pocket, structure analysis of PcUP1 with bound ligands, active site structure and substrate binding, overview
additional information
structure of the active center of enzyme UDP from Shewanella oneidensis strain MR-1 (SoUDP) in complex with uridine and sulfate (code PDB 4R2W), structure-function analysis. In the SoUDP active center, uridine is in high-energy syn-conformation, and the ribose residue acquires a conformation close to planar
additional information
-
the formation of a hydrogen-bond network between the 2'-hydroxy group of uridine and atoms of the active-site residues of uridine phosphorylase leads to conformational changes of the ribose moiety of uridine, resulting in an increase in the reactivity of uridine compared to thymidine. Since the binding of thymidine to residues of uridine phosphorylase causes a smaller local strain of the beta-N1-glycosidic bond in this the substrate compared to the uridine molecule, the beta-N1-glycosidic bond in thymidine is more stable and less reactive than that in uridine. The phosphate anion, which is the second substrate bound at the active site, interacts simultaneously with the residues of the beta5-strand and the beta1-strand through hydrogen bonding, thus securing the gate loop in a conformation so that the active site of the enzyme molecule becomes inaccessible for nucleoside binding. Structures of VchUPh in complexes with thymine and uracil are prepared for molecular docking of the second substrates of the reverse reaction (ribose 1-phosphate and 2-deoxyribose 1-phosphate). The phosphate-binding F site of the EF homodimer of VchUPh is formed by hydrophilic residues, four of which belong to the F subunit (Thr93/F, Gly25/F, Arg29/F, and Arg90/F), and the fifth residue (Arg47/E) belongs to the E subunit. Residues Gln165, Arg167, and Arg222 play key roles in the binding of the pyrimidine moiety of the ligand (uridine, thymidine, uracil, and thymine) to VchUPh. Residues Glu197 and Thr93, as well as His7 of the adjacent subunit, play the main role in the binding of the furanose moiety of thymidine and uridine. The uridine (URI) molecule occupies the whole nucleoside-binding site of the VchUPh molecule. The URI molecule interacts with the nucleoside-binding site in the structure of VchUPh complexed with uridine (ID PDB: 5C80) through hydrogen bonds
additional information
-
strict conservation of UP1 key residues in the binding pocket, structure analysis of PcUP1 with bound ligands, active site structure and substrate binding, overview
-
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PDB
SCOP
CATH
UNIPROT
ORGANISM