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Information on EC 1.17.3.2 - xanthine oxidase
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1.17.3.2 xanthine oxidaseIUBMB Comments
An iron-molybdenum flavoprotein (FAD) containing [2Fe-2S] centres. Also oxidizes hypoxanthine, some other purines and pterins, and aldehydes, but is distinct from EC 1.2.3.1, aldehyde oxidase. Under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 O2.- + 2 H+. The mammalian enzyme predominantly exists as an NAD-dependent dehydrogenase (EC 1.17.1.4, xanthine dehydrogenase). During purification the enzyme is largely converted to the O2-dependent xanthine oxidase form (EC 1.17.3.2). The conversion can be triggered by several mechanisms, including the oxidation of cysteine thiols to form disulfide bonds [4,5,7,10] [which can be catalysed by EC 1.8.4.7, enzyme-thiol transhydrogenase (glutathione-disulfide) in the presence of glutathione disulfide] or limited proteolysis, which results in irreversible conversion. The conversion can also occur in vivo [4,6,10].
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Word Map
- 1.17.3.2
- allopurinol
-
uric
- dismutase
- catalase
- sod
- endothelial
- xx
- malondialdehyde
-
reperfusion
- purine
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hyperuricemia
- artery
- ischemia
- gout
- karyotype
-
turner
- myocardial
- gsh
- pulmonary
- myeloperoxidase
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ischemia-reperfusion
- gonad
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hermaphrodite
- oxypurinol
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tbars
-
spin
- urate
-
thiobarbituric
-
sex-determining
- dysgenesis
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x-chromosome
-
chemiluminescence
- molybdenum
- caffeine
- gsh-px
-
fenton
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masculinization
-
acid-reactive
-
sex-reversed
-
feminization
- tungsten
-
hypouricemic
-
oxygen-derived
-
monosomy
- medicine
- diagnostics
-
urate-lowering
-
oxidase-derived
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self-fertilizing
- cyp2a6
-
nondisjunction
- drug development
-
radical-generating
- biotechnology
- pharmacology
- synthesis
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
AXOR, EC 1.1.3.22, EC 1.2.3.2., hypoxanthine oxidase, hypoxanthine-xanthine oxidase, hypoxanthine:oxygen oxidoreductase, More, oxidase, xanthine, Schardinger enzyme, xanthine dehydrogenase/oxidase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
EC 1.1.3.22
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EC 1.2.3.2.
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formerly
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hypoxanthine oxidase
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hypoxanthine-xanthine oxidase
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hypoxanthine:oxygen oxidoreductase
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oxidase, xanthine
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Schardinger enzyme
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xanthine oxidase
xanthine oxidoreductase
xanthine:O2 oxidoreductase
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xanthine:xanthine oxidase
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XO
XOD
XOR
additional information
xanthine oxidase
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one of two conformational stages of the enzyme with different activities, the second is xanthine dehydrogenase
xanthine oxidoreductase
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xanthine oxidoreductase
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xanthine oxidoreductase can exists in a dehydrogenase form, XD, and an oxidase form, XO
XOR
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xanthine oxidoreductase can exists in a dehydrogenase form, XD, and an oxidase form, XO
additional information
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XOR can adopt its XOR xanthone oxidoreductase form EC 1.17.3.2, and its xanthine dehydrogenase form, XDH, EC 1.17.1.4
additional information
XOR can adopt its XOR xanthine oxidoreductase form EC 1.17.3.2, and its xanthine dehydrogenase form, XDH, EC 1.17.1.4
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
xanthine + H2O + O2 = urate + H2O2
hydrogen-bonding arrangement of the substrate-bound complex at the active site, and proposed mechanism of the purine oxidation reaction by XOR
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xanthine + H2O + O2 = urate + H2O2
catalytic mechanism of xanthine oxidoreductase, overview
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xanthine + H2O + O2 = urate + H2O2
favored mechanism for the reaction with xanthine, overview
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xanthine + H2O + O2 = urate + H2O2
reaction mechanism for xanthine oxidase, overview. Catalysis is initiated by base-assisted nucleophilic attack of the equatorial Mo-OH on the C-8 carbon of xanthine with concomitant hydride transfer from C-8 to Mo=S, which simultaneously results in reduction of Mo(VI) to Mo(IV). Reoxidation of the molybdenum center occurs by electron transfer to the other redox-active centers of the enzyme, accompanied by deprotonation of the Mo-SH bond and displacement of bound product by hydroxide from solvent to regenerate the Mo-OH group
xanthine + H2O + O2 = urate + H2O2
reaction mechanism of XOR and binding modes of the substrate xanthine, overview. The oxidative hydroxylation of purine substrates takes place at the molybdenum center. Reducing equivalents introduced there are then transferred via two [2Fe-2S] centers to the FAD cofactor where reduction of the physiological electron acceptors occurs, NAD+ in the case of the dehydrogenase form, XDH, or O2 in the oxidase form, XO, of the enzyme occur
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xanthine + H2O + O2 = urate + H2O2
reaction mechanism of XOR and binding modes of the substrate xanthine, overview. The oxidative hydroxylation of purine substrates takes place at the molybdenum center. Reducing equivalents introduced there are then transferred via two [2Fe-2S] centers to the FAD cofactor where reduction of the physiological electron acceptors occurs, NAD+ in the case of the dehydrogenase form, XDH, or O2 in the oxidase form, XO, of the enzyme occur
xanthine + H2O + O2 = urate + H2O2
reaction mechanism, detailed overview. The reaction is initiated by proton abstraction from the Mo-OH group by Glu1261, the active-site base, followed by nucleophilic attack on the carbon to be hydroxylated, and hydride transfer to the Mo-S double bond. Suitable substrate orientation, overview. Arg880 is involved in stablizing the transition state in the course of nucleophilic attack, overview
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xanthine + H2O + O2 = urate + H2O2
mechanism of the reductive half-reaction of xanthine oxidase
xanthine + H2O + O2 = urate + H2O2
the catalytic reaction of xanthine oxidase is initiated by abstraction of a proton from the Mo-OH group by a conserved active site glutamate residue. The oxidative hydroxylation of xanthine to uric acid takes place at the molybdenum center and results in the two-electron reduction of the metal from Mo(VI) to Mo(IV). The enzyme is subsequently re-oxidized by NAD+ or molecular oxygen in a reaction that occurs at the FAD cofactor
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xanthine + H2O + O2 = urate + H2O2
the catalytic reaction of xanthine oxidase is initiated by abstraction of a proton from the Mo-OH group by a conserved active site glutamate residue. The oxidative hydroxylation of xanthine to uric acid takes place at the molybdenum center and results in the two-electron reduction of the metal from Mo(VI) to Mo(IV). The enzyme is subsequently re-oxidized by NAD+ or molecular oxygen in a reaction that occurs at the FAD cofactor
Bacillus pumilus RL-2d
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xanthine + H2O + O2 = urate + H2O2
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
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redox reaction
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reduction
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PATHWAY SOURCE
PATHWAYS
KEGG
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SYSTEMATIC NAME
IUBMB Comments
xanthine:oxygen oxidoreductase
An iron-molybdenum flavoprotein (FAD) containing [2Fe-2S] centres. Also oxidizes hypoxanthine, some other purines and pterins, and aldehydes, but is distinct from EC 1.2.3.1, aldehyde oxidase. Under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 O2.- + 2 H+. The mammalian enzyme predominantly exists as an NAD-dependent dehydrogenase (EC 1.17.1.4, xanthine dehydrogenase). During purification the enzyme is largely converted to the O2-dependent xanthine oxidase form (EC 1.17.3.2). The conversion can be triggered by several mechanisms, including the oxidation of cysteine thiols to form disulfide bonds [4,5,7,10] [which can be catalysed by EC 1.8.4.7, enzyme-thiol transhydrogenase (glutathione-disulfide) in the presence of glutathione disulfide] or limited proteolysis, which results in irreversible conversion. The conversion can also occur in vivo [4,6,10].
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CAS REGISTRY NUMBER
COMMENTARY
9002-17-9
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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
(carboxymethyl)cellulose with endohydrolysed (1->4)-beta-D-glucosidic linkages + H2O + O2
?
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-
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r
1-methyl-2-hydroxypurine + H2O + O2
1-methyl-2-hydroxy-7,9-dihydropurin-8-one + H2O2
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-
-
?
2-amino-4-hydroxypterin + H2O + O2
? + H2O2
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substrate inhibition kinetic pattern
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-
?
2-amino-6-chloro-purine + H2O + O2
2-amino-6-chloro-7,9-dihydro-purin-8-one + H2O2
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-
-
-
?
2-mercaptopurine + H2O + O2
8-hydroxy-2-mercaptopurine + H2O2
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no conversion to 2-thioxanthine
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-
?
3-hydroxy-4-methoxybenzaldehyde + H2O + O2
3-hydroxy-4-methoxybenzoate + H2O2
-
-
-
-
?
4-hydroxy-3-methoxybenzaldehyde + H2O + O2
4-hydroxy-3-methoxybenzoate + H2O2
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-
-
-
?
5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]-3H-pyrimidin-4-one + H2O + O2
?
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-
-
-
?
6'-deoxyacyclovir + H2O + O2
acyclovir + H2O2
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prodrug of the antiviral agent acyclovir
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?
6,8-dihydroxypurine + H2O + O2
? + H2O2
6,8-dihydroxypurine binding structure, overview
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?
6-mercaptopurine + H2O + O2
6-mercapto-7,9-dihydropurin-8-one + H2O2
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4.4% of activity with xanthin
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?
FYX-051 + O2 + H2O
?
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the structure of bovine XOR exposed to the slow-reacting substrate FYX-051 shows a covalent intermediate of the hydroxylation reaction, in which the hydroxyl oxygen bridged the molybdenumatom and the acceptor carbon atom of the aromatic ring of the substrate
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?
glyceryl trinitrate + NADH
? + NAD+ + H2O
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further reaction of organic nitrite with thiols or ascorbate leads to generation of NO or nitrosothiols
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?
isosorbide dinitrate + NADH
? + NAD+ + H2O
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further reaction of organic nitrite with thiols or ascorbate leads to generation of NO or nitrosothiols
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?
lumazine + H2O + O2
? + H2O2
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classical Michaelis-Menten hyperbolic saturation kinetic pattern
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?
nitrite + 2,3-dihydroxybenzaldehyde
NO + ?
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NO generation occurs under aerobic conditions and is regulated by O2 tension, pH, nitrite, and reducing substrate concentrations
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?
organic nitrate + NADH
organic nitrite + NAD+ + H2O
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organic nitrite is the initial product in the process of xanthine oxidase mediated organic nitrate biotransformation and is the precursor of NO and nitrosothiols, serving as the link between organic nitrate and soluble guanylyl cyclase
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?
xanthine + 2,6-dichlorophenolindophenol + H2O
urate + reduced 2,6-dichlorophenolindophenol
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?
6-mercaptopurine + 2 H2O + 2 O2
6-thiouric acid + 2 H2O2
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production of superoxide radicals
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?
6-mercaptopurine + 2 H2O + 2 O2
6-thiouric acid + 2 H2O2
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a two-step reaction with 6-thioxanthine as intermediate
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?
6-mercaptopurine + 2 H2O + 2 O2
6-thiouric acid + 2 H2O2
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an anticancer prodrug, no activation by xanthine oxidase but conversion to the inactive metabolite 6-thiouric acid, catabolism, overview
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?
adenine + H2O + O2
6-amino-7,9-dihydropurin-8-one + H2O2
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no activity with adenine
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?
allopurinol + H2O + O2
oxypurinol + H2O2
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allopurinol is a conventional substrate that generates superoxide radicals during its oxidation
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?
allopurinol + H2O + O2
oxypurinol + H2O2
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allopurinol is a substrate and a competitive inhibitor for xanthine oxidase, it binds irreversibly at the active site reducing molybdenum VI to IV
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?
allopurinol + H2O + O2
oxypurinol + H2O2
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allopurinol is a substrate and a competitive inhibitor for xanthine oxidase, it binds irreversibly at the active site reducing molybdenum VI to IV
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
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?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
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enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
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?
guanine + H2O + O2
2-amino-7,9-dihydro-1H-purine-6,8-dione + H2O2
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53.3% of activity with xanthin
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?
hypoxanthine + 2 H2O + 2 O2
urate + 2 H2O2
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a two-step reaction with xanthine as intermediate, production of superoxide radicals
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?
hypoxanthine + 2 H2O + 2 O2
urate + 2 H2O2
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via intermediate xanthine formation, production of superoxide radicals
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?
hypoxanthine + 2 H2O + 2 O2
urate + 2 H2O2
hypoxanthine binding structure, overview
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?
hypoxanthine + 2 H2O + 2 O2
urate + 2 H2O2
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92.3% of activity with xanthin
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?
hypoxanthine + 2 H2O + 2 O2
urate + 2 H2O2
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92.3% of activity with xanthin
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?
hypoxanthine + 2 H2O + 2 O2
urate + 2 H2O2
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production of superoxide radicals
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-
?
nitrate + NADH
nitrite + NAD+ + H2O
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reaction can be an important source of NO production in ischemic tissues
-
-
?
nitrite + NADH
NO + NAD+ + H2O
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reaction can be an important source of NO production in ischemic tissues
-
-
?
nitrite + NADH
NO + NAD+ + H2O
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NO generation occurs under aerobic conditions and is regulated by O2 tension, pH, nitrite, and reducing substrate concentrations
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?
nitrite + xanthine
NO + ?
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NO generation occurs under aerobic conditions and is regulated by O2 tension, pH, nitrite, and reducing substrate concentrations
-
-
?
pteridine + H2O + O2
?
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and derivatives, e.g.: 4-amino-7-hydroxy pteridine, 4-hydroxy-7-azapteridine
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-
?
purine + H2O + O2
7,9-dihydropurin-8-one + H2O2
-
purine and derivatives
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?
purine + H2O + O2
7,9-dihydropurin-8-one + H2O2
-
purine and derivatives
-
?
purine + H2O + O2
7,9-dihydropurin-8-one + H2O2
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23.3% of activity with xanthine
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?
purine + H2O + O2
7,9-dihydropurin-8-one + H2O2
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purine and derivatives
-
?
purine + H2O + O2
7,9-dihydropurin-8-one + H2O2
-
purine and derivatives
-
?
pyrimidine derivatives + H2O + O2
?
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7-hydroxy-(1,2,5)-thiadiazolo(3,4-d)-pyrimidine
-
-
?
pyrimidine derivatives + H2O + O2
?
-
7-hydroxy-(1,2,5)-thiadiazolo(3,4-d)-pyrimidine
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-
?
xanthine + H2O + O2
urate + H2O2
-
-
-
-
?
xanthine + H2O + O2
urate + H2O2
-
-
-
?
xanthine + H2O + O2
urate + H2O2
-
production of superoxide radicals
-
-
?
xanthine + H2O + O2
urate + H2O2
orientation of xanthine in the active site of xanthine oxidoreductase,structure, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
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production of superoxide radicals, determination of a reactive intermediate oxygen species relevant to superoxide and hydroxyl radicals, method optimization using electron transfer via H2O2, luminol, and aminophthallate, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
catalytically relevant binding mode of the substrate xanthine, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
effects of variations in the cofactor, the substrate, and the active site residue Glu802 on the reaction mechanism, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
substrate orientation and catalytic specificity, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
production of superoxide radicals
-
-
?
xanthine + H2O + O2
urate + H2O2
-
the enzyme is involved in development of ischemia and equine laminitis, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
the enzyme plays a role in the development of distant organ dysfunction after abdominal surgery, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
-
-
-
?
xanthine + H2O + O2
urate + H2O2
-
old persons show higher enzyme expression and activity than young persons which promotes a worse prognosis for patients with chronic heart failure due to the increased contents of risk factor urate, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
production of reactive oxygen species via superoxide radicals involved in endothelial dysfunction
-
-
?
xanthine + H2O + O2
urate + H2O2
-
production of superoxide radicals
-
-
?
xanthine + H2O + O2
urate + H2O2
-
roles of active site residues E308 and R881 in binding and activation of purine substrate, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
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the enzyme plays a role in the development of distant organ dysfunction after abdominal surgery, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
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urate is involved in development of endothelial dysfunction, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
xanthine oxidase-derived extracellular superoxide anions stimulate activator protein 1 activity and hypertrophy in vascular smooth muscle via c-Jun N-terminal kinase and p38 mitogen-activated protein kinases, xanthine and xanthine oxidase treatment of smooth muscle cells lead to increased cell growth and size, overview
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-
?
xanthine + H2O + O2
urate + H2O2
-
production of superoxide radicals, mechanism of stepwise enzyme reduction during catalysis, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
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production of superoxide radicals
-
-
?
xanthine + H2O + O2
urate + H2O2
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xanthine oxidase inhibition, meaning a decrease in myocardial oxidative stress, improves left ventricular dysfunction in dilated cardiomyopathic hamsters, modelling, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
production of superoxide radicals
-
-
?
xanthine + H2O + O2
urate + H2O2
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production of superoxide radicals, treatment with an enzyme inhibitor largely prevents the development of endothelial dysfunction and atherosclerosis in mice
-
-
?
xanthine + H2O + O2
urate + H2O2
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the enzyme plays a role in the development of distant organ dysfunction after abdominal surgery, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
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production of superoxide radicals
-
-
?
xanthine + H2O + O2
urate + H2O2
-
-
-
-
?
xanthine + H2O + O2
urate + H2O2
-
xanthine oxidoreductase, XOR, can exist in a dehydrogenase form, XD, and an oxidase form, XO. Part of total XOR activity in peroxisomes is XO activity. The major function of XOR activity in the cytoplasm of rat liver parenchymal cells and in sinusoidal cells is not the production of O2 radicals, but rather the production of uric acid which can act as a potent antioxidant
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-
?
xanthine + H2O + O2
urate + H2O2
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old animals show higher enzyme expression and activity than young rats which promotes a worse prognosis for patients with chronic heart failure due to the increased contents of risk factor urate, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
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production of superoxide radicals
-
-
?
xanthine + H2O + O2
urate + H2O2
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production of superoxide radicals can be induced by gama-irradiation and contributes to oxidative stress and endothelial nitroredox imbalance with resultant endothelial dysfunction and altered vascular mechanics, mechanism and regulation, overview
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-
?
xanthine + H2O + O2
urate + H2O2
the enzyme is involved in regulation of reactive oxygen species in the functional response of veins and arteries to angiotensin II, norepinephrine, and acetylcholine
-
-
?
xanthine + H2O + O2
urate + H2O2
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the enzyme plays a role in the development of distant organ dysfunction after abdominal surgery, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
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urate is involved in development of endothelial dysfunction, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
xanthine oxidase inhibition by febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in hyperuricaemia, experimentally-induced by inhibition of uricase with oxonic acid, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
xanthine oxidase is an important source of reactive oxygen species that contributes to neurovascular dysfunction in experimental diabetes, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
production of superoxide radicals, mechanism of stepwise enzyme reduction during catalysis, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
catalytically relevant binding mode of the substrate xanthine, overview
-
-
?
xanthine + H2O + O2
uric acid + H2O2
-
Arthrobacter S-2 enzyme: relatively specific
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor ferricyanide
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor 2,6-dichlorophenolindophenol
-
?
xanthine + H2O + O2
uric acid + H2O2
-
Arthrobacter S-2 enzyme: relatively specific
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor ferricyanide
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor 2,6-dichlorophenolindophenol
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor methylene blue
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor methylene blue
under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 H+ + 2 O2-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor NAD+
under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 H+ + 2 O2-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor O2
under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 H+ + 2 O2-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor quinones
under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 H+ + 2 O2-
?
xanthine + H2O + O2
uric acid + H2O2
-
specificity for electron acceptor is low
-
?
xanthine + H2O + O2
uric acid + H2O2
-
specificity for electron acceptor is low
under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 H+ + 2 O2-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor triphenyltetrazolium chloride, phenazine methosulfate, nitrate, cytochrome c, ferritin
-
?
xanthine + H2O + O2
uric acid + H2O2
-
enzyme also oxidizes hypoxanthine, some other purines, pterines and aldehydes, i.e. possesses the activity of EC 1.2.3.1, probably acts on the hydrated derivatives of these substrates
under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 H+ + 2 O2-
?
xanthine + H2O + O2
uric acid + H2O2
-
low specificity to substrate
under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 H+ + 2 O2-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor ferricyanide
under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 H+ + 2 O2-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor 2,6-dichlorophenolindophenol
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor 2,6-dichlorophenolindophenol
under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 H+ + 2 O2-
?
xanthine + H2O + O2
uric acid + H2O2
-
the enzyme accelerates reaction rate via base-catalyzed chemistry in which a Mo-OH group undertakes nucleophilic attack on the carbon center to be hydroxylated, with concomitant hydride transfer to a catalytically essential Mo=S group in the molybdenum coordination sphere. This chemistry appears to proceed via obligate two-electron chemistry rather than in individual steps to yield a reduced enzyme product complex with product coordinmated to the active site molybdenum by means of the newly introduced hydroxyl group in a sinple end-on fashion. Product displacement by hydroxide and electron transfer to other redox-active centers in the enzyme complete the catalytic sequence
-
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor O2
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor O2
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor O2
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor ferricyanide
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor 2,6-dichlorophenolindophenol
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor O2
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor ferricyanide
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor 2,6-dichlorophenolindophenol
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor O2
-
?
xanthine + H2O + O2
uric acid + H2O2
-
electron acceptor O2
enzyme contributes to the oxidant stress component of ischemia-reperfusion injury to intestine and liver, O2- production decreases with increasing substrate concentrations
?
xanthine + NO2-
uric acid + NO
-
oxidation of the enzyme by NO2- or reduction by xanthine take place at the molybdenum site
-
-
?
xanthine + O2 + H2O
urate + H2O2
-
xanthine oxidoreductase exists in two forms. The protein normally exists as xanthine dehydrogenase, XDH, EC 1.17.1.4, and utilizes NAD+ as its final electron acceptor in catalysis. Under certain conditions, most notably schemia and/or hypoxia, XDH can be converted to an oxidase form, XO, which can no longer reduce NAD+ and instead utilizes O2 exclusively as the terminal electron acceptor in the course of turnover. This conversion may occur either by oxidation of sulfhydryl groups and/or by limited proteolysis
-
-
?
xanthine + O2 + H2O
urate + H2O2
-
binding modes of the substrate xanthine and mechanism of its hydroxylation, overview
-
-
?
xanthine + O2 + H2O
urate + H2O2
-
conversion of xanthine to uric acid at the molybdenum-containing active site
-
-
?
xanthine + O2 + H2O
urate + H2O2
-
binding modes of the substrate xanthine and mechanism of its hydroxylation, overview
-
-
?
additional information
?
-
-
XDH, EC 1.17.1.4, can be converted into xanthine oxidase, XO, either reversibly by oxidation of the sulfhydryl groups of two conserved cysteine residues. Under physiological conditions the XDH form appears to dominate with 80% over the XO form with 20%
-
-
?
additional information
?
-
-
XDH, EC 1.17.1.4, can be converted into xanthine oxidoreductase, XO, either reversibly by oxidation of the sulfhydryl groups of two conserved cysteine residues. Under physiological conditions the XDH form appears to dominate with 80% over the XO form with 20%
-
-
?
additional information
?
-
-
AtXDH1 is capable of oxidizing NADH with concomitant formation of NAD+ and superoxide, the specific activity of recombinant AtXDH1 with NADH as substrate is about 15times higher than the activity with xanthine accompanied by a doubling in superoxide production and is dependent on sulfurated molybdenum cofactor, overview. FAD is crucial for NADH-based superoxide formation of AtXDH1, whereas the molybdenum cofactor has only little or no influence on the activity, residues E831, R909, E1297, W364, and Y421 are involved
-
-
?
additional information
?
-
-
AtXDH1 is capable of oxidizing NADH with concomitant formation of NAD+ and superoxide, the specific activity of recombinant AtXDH1 with NADH as substrate is about 15times higher than the activity with xanthine accompanied by a doubling in superoxide production, overview. FAD is crucial for NADH-based superoxide formation of AtXDH1, whereas the molybdenum cofactor has only little or no influence on the activity, residues E831, R909, E1297, W364, and Y421 are involved
-
-
?
additional information
?
-
-
the catalytic reaction of xanthine oxidase is initiated by abstraction of a proton from the Mo-OH group by a conserved active site glutamate residue. The oxidative hydroxylation of xanthine to uric acid takes place at the molybdenum center and results in the two-electron reduction of the metal from Mo(VI) to Mo(IV). The enzyme is subsequently re-oxidized by NAD+ or molecular oxygen in a reaction that occurs at the FAD cofactor
-
-
?
additional information
?
-
Bacillus pumilus RL-2d
-
the catalytic reaction of xanthine oxidase is initiated by abstraction of a proton from the Mo-OH group by a conserved active site glutamate residue. The oxidative hydroxylation of xanthine to uric acid takes place at the molybdenum center and results in the two-electron reduction of the metal from Mo(VI) to Mo(IV). The enzyme is subsequently re-oxidized by NAD+ or molecular oxygen in a reaction that occurs at the FAD cofactor
-
-
?
additional information
?
-
-
addition of xanthine oxidase to a solution of acetaldehyde and ascorbate increases the rate of ascorbate oxidation, due to the action of superoxide radicals generated in the process
-
-
?
additional information
?
-
-
hydroxyl free radicals generated by the hypoxanthine/xanthine oxidase/Fe system are implicated in oxidation of dibromoacetonitrile to CN-
-
-
?
additional information
?
-
-
5-chloro-6-methyl-3H-pyrimidin-4-one is no substrate
-
-
?
additional information
?
-
-
evaluation of a HPLC detection method for enzyme reaction products, overview
-
-
?
additional information
?
-
-
nature and position of functional group on thiopurine substrates influence activity of xanthine oxidase
-
-
?
additional information
?
-
-
the enzyme also catalyzes the oxidation of hypoxanthine to xanthine as xanthine dehydrogenase, EC 1.17.1.4, using NAD+ a oxidant substrate, XDH, mechanism of transition between XOR and XDH, after conversion reversibly via disulfide formation or irreversibly via proteolytic cleavage involving residues R335, R427, W336, and F549, overview
-
-
?
additional information
?
-
-
during inflammatory conditions, reversible oxidation of critical cysteine residues or limited proteolysis converts xanthine dehydrogenase, XDH, EC 1.17.1.4, to xanthine oxidase, XO, which reduces O2 to superoxide and H2O2. Conversion to XO, however, is not requisite for reactive oxygen species production, as XDH displays partial oxidase activity. Xanthine oxidoreductase generates proinflammatory oxidants and secondary nitrating species, with inhibition of XOR proving beneficial in a variety of disorders
-
-
?
additional information
?
-
-
the oxidation of xanthine takes place at the molybdenum center, and the electrons thus introduced are rapidly transferred to FAD via the Fe-SI and Fe-SII centers. Glu1261, located near the Mo-OH in the salicylate bound-form of XOR, initiates catalysis by deprotonating the Mo-OH group
-
-
?
additional information
?
-
-
quantum mechanical/molecular mechanical study of the reductive half-reaction of wild-type xanthine oxidase, overview
-
-
?
additional information
?
-
-
role of Glu802 is facilitating the tautomerization of hypoxanthine in the course of hydroxylation by the enzyme, substrate binding structures, overview
-
-
?
additional information
?
-
-
xanthine and lumazine are good substrates, while 2-hydroxy-6-methylpurine is a slow and poor substrate
-
-
?
additional information
?
-
scavenging activities of 1,1-diphenyl-2-picryhydrazyl (DPPH) radical and O2 generated with phenazine methosulfate (PMS) and NADH,overview
-
-
?
additional information
?
-
-
the enzyme shows two conformational stages with different activities: one is the xanthine oxidase, the second is xanthine dehydrogenase, EC 1.17.1.4
-
-
?
additional information
?
-
-
xanthine oxidase inhibition in small intestine ischemia-reperfusion injury leads to reduction in neutrophil infiltration
-
-
?
additional information
?
-
-
enzyme inhibitors exert beneficial effect on endothelial dysfunction, mechanisms, overview, mechanism of action in cardiovascular disease, overview
-
-
?
additional information
?
-
-
phosphatidylinositol 3-kinase and xanthine oxidase regulate nitric oxide and reactive oxygen species productions by apoptotic lymphocyte microparticles in endothelial cells, overview
-
-
?
additional information
?
-
-
the enzyme activity, but not oxidative damage parameters, at the time of sepsis diagnosis is significantly higher in non-survival septic patients than in survival patients, overview
-
-
?
additional information
?
-
-
the enzyme and its superoxide producing activity are involved in endothelial dysfunction in atherosclerosis, overview
-
-
?
additional information
?
-
-
the enzyme catalyzes the oxidation of endogenous and exogenous purines and pyrimidines
-
-
?
additional information
?
-
-
the enzyme is induced by heat shock, the reactive oxygen species produced by heat shock may play an important role in the heat shock-induced activation of MAPKs, which can induce MMP-1 and-9 expressions, overview
-
-
?
additional information
?
-
-
evaluation of a HPLC detection method for enzyme reaction products, overview
-
-
?
additional information
?
-
-
single nucleotide polymorphisms alter the substrate specificity of the enzyme, overview
-
-
?
additional information
?
-
-
the enzyme interacts with the Toll-like receptor-4, TLR-4, inducing proinflammatory cytokine production, extracellular superoxide production by the enzyme leads to nuclear translocation of nuclear factor-kappaB and increased neutrophil production of the NFkappaB-dependent cytokines tumor necrosis factor-alpha and macrophage inhibitory protein-2 mediated by TLR-4, overview
-
-
?
additional information
?
-
-
the enzyme is capable to generate superoxide radicals and H2O2 derived from it, the synthesis of the radicals is increased upon a temperature shift from 30°C to 45°C and by photosensitization of tumor cells with a hematoporphyrin derivative, overview
-
-
?
additional information
?
-
-
the enzyme, together with mitochondrial complex III, is responsible for reactive oygen species production in ischemic muscle, they act in tissue damage after ischemic-reperfusion, regulation, overview
-
-
?
additional information
?
-
-
xanthine oxidase inhibition in small intestine ischemia-reperfusion injury leads to prevention of intestine necrosis
-
-
?
additional information
?
-
-
chronic enzyme inhibition by allopurinol or febuxostat cannot prevent or treat the progression of congestive heart failure induced by coronary artery ligation in rabbits, overview
-
-
?
additional information
?
-
-
xanthine oxidase is necessary during the physiological involution of tissues
-
-
?
additional information
?
-
-
enzyme inhibitors exert beneficial effect on endothelial dysfunction, mechanisms, overview, mechanism of action in cardiovascular disease, overview
-
-
?
additional information
?
-
-
xanthine oxidase inhibition in small intestine ischemia-reperfusion injury leads to reduction in villar necrosis, reduced intestinal MPO levels, reduced circulating neutrophil priming and reduction in pulmonary damage, prevention of permeability changes in intestinal mucosa, reduction in length of necrotic small bowel by 60%, reduction in intestinal apoptosis and tissue MDA levels; reduction in plasma MDA levels and improvement in renal function, and improved small intestine anastomotic healing and animal survival, overview
-
-
?
additional information
?
-
-
xanthine oxidase-derived reactive oxygen species contribute to the development of D-galactosamine-induced liver injury in rats, overview
-
-
?
additional information
?
-
-
enzyme inhibition by orange juice and hesperetin participates in preventing oxidative stress by enhancing total antioxidant capacity and decreasing lipid peroxidation, overview
-
-
?
additional information
?
-
-
the oxidation of xanthine takes place at the molybdenum cofactor, and the electrons thus introduced are rapidly transferred to FAD via the Fe-SI and Fe-SII centers. Glu1261, located near the Mo-OH in the salicylate bound-form of XOR, initiates catalysis by deprotonating the Mo-OH group
-
-
?
additional information
?
-
purified recombinant wild-type and DELTAC mutant enzymes both exhibit mostly xanthine oxidase activity
-
-
?
additional information
?
-
ionized Glu232 of wild-type enzyme plays an important role in catalysis by discriminating against the monoanionic form of xanthine. Proposed orientations of xanthine binding in the active site of xanthine oxidoreductase, using the predominant tautomers of the neutral and monoanionic forms of xanthine, overview
-
-
?
additional information
?
-
-
xanthine oxidase catalyzes the oxidation of hypoxanthine to xanthine to uric acid, and oxygen radicals that are formed as a by-product at both of these oxidation steps may participate in plant defense reactions
-
-
?
additional information
?
-
-
xanthine oxidase catalyzes the oxidation of hypoxanthine to xanthine to uric acid, and oxygen radicals that are formed as a by-product at both of these oxidation steps may participate in plant defense reactions
-
-
?
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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
nitrate + NADH
nitrite + NAD+ + H2O
-
reaction can be an important source of NO production in ischemic tissues
-
-
?
nitrite + NADH
NO + NAD+ + H2O
-
reaction can be an important source of NO production in ischemic tissues
-
-
?
organic nitrate + NADH
organic nitrite + NAD+ + H2O
-
organic nitrite is the initial product in the process of xanthine oxidase mediated organic nitrate biotransformation and is the precursor of NO and nitrosothiols, serving as the link between organic nitrate and soluble guanylyl cyclase
-
-
?
6-mercaptopurine + 2 H2O + 2 O2
6-thiouric acid + 2 H2O2
-
an anticancer prodrug, no activation by xanthine oxidase but conversion to the inactive metabolite 6-thiouric acid, catabolism, overview
-
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
-
?
hypoxanthine + 2 H2O + 2 O2
urate + 2 H2O2
-
production of superoxide radicals
-
-
?
xanthine + H2O + O2
urate + H2O2
-
-
-
-
?
xanthine + H2O + O2
urate + H2O2
-
-
-
?
xanthine + H2O + O2
urate + H2O2
-
catalytically relevant binding mode of the substrate xanthine, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
the enzyme is involved in development of ischemia and equine laminitis, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
the enzyme plays a role in the development of distant organ dysfunction after abdominal surgery, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
old persons show higher enzyme expression and activity than young persons which promotes a worse prognosis for patients with chronic heart failure due to the increased contents of risk factor urate, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
production of reactive oxygen species via superoxide radicals involved in endothelial dysfunction
-
-
?
xanthine + H2O + O2
urate + H2O2
-
production of superoxide radicals
-
-
?
xanthine + H2O + O2
urate + H2O2
-
roles of active site residues E308 and R881 in binding and activation of purine substrate, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
the enzyme plays a role in the development of distant organ dysfunction after abdominal surgery, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
urate is involved in development of endothelial dysfunction, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
xanthine oxidase-derived extracellular superoxide anions stimulate activator protein 1 activity and hypertrophy in vascular smooth muscle via c-Jun N-terminal kinase and p38 mitogen-activated protein kinases, xanthine and xanthine oxidase treatment of smooth muscle cells lead to increased cell growth and size, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
xanthine oxidase inhibition, meaning a decrease in myocardial oxidative stress, improves left ventricular dysfunction in dilated cardiomyopathic hamsters, modelling, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
production of superoxide radicals
-
-
?
xanthine + H2O + O2
urate + H2O2
-
production of superoxide radicals, treatment with an enzyme inhibitor largely prevents the development of endothelial dysfunction and atherosclerosis in mice
-
-
?
xanthine + H2O + O2
urate + H2O2
-
the enzyme plays a role in the development of distant organ dysfunction after abdominal surgery, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
xanthine oxidoreductase, XOR, can exist in a dehydrogenase form, XD, and an oxidase form, XO. Part of total XOR activity in peroxisomes is XO activity. The major function of XOR activity in the cytoplasm of rat liver parenchymal cells and in sinusoidal cells is not the production of O2 radicals, but rather the production of uric acid which can act as a potent antioxidant
-
-
?
xanthine + H2O + O2
urate + H2O2
-
old animals show higher enzyme expression and activity than young rats which promotes a worse prognosis for patients with chronic heart failure due to the increased contents of risk factor urate, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
production of superoxide radicals can be induced by gama-irradiation and contributes to oxidative stress and endothelial nitroredox imbalance with resultant endothelial dysfunction and altered vascular mechanics, mechanism and regulation, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
the enzyme is involved in regulation of reactive oxygen species in the functional response of veins and arteries to angiotensin II, norepinephrine, and acetylcholine
-
-
?
xanthine + H2O + O2
urate + H2O2
-
the enzyme plays a role in the development of distant organ dysfunction after abdominal surgery, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
urate is involved in development of endothelial dysfunction, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
xanthine oxidase inhibition by febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in hyperuricaemia, experimentally-induced by inhibition of uricase with oxonic acid, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
-
xanthine oxidase is an important source of reactive oxygen species that contributes to neurovascular dysfunction in experimental diabetes, overview
-
-
?
xanthine + H2O + O2
urate + H2O2
catalytically relevant binding mode of the substrate xanthine, overview
-
-
?
xanthine + O2 + H2O
urate + H2O2
-
xanthine oxidoreductase exists in two forms. The protein normally exists as xanthine dehydrogenase, XDH, EC 1.17.1.4, and utilizes NAD+ as its final electron acceptor in catalysis. Under certain conditions, most notably schemia and/or hypoxia, XDH can be converted to an oxidase form, XO, which can no longer reduce NAD+ and instead utilizes O2 exclusively as the terminal electron acceptor in the course of turnover. This conversion may occur either by oxidation of sulfhydryl groups and/or by limited proteolysis
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XDH, EC 1.17.1.4, can be converted into xanthine oxidase, XO, either reversibly by oxidation of the sulfhydryl groups of two conserved cysteine residues. Under physiological conditions the XDH form appears to dominate with 80% over the XO form with 20%
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XDH, EC 1.17.1.4, can be converted into xanthine oxidoreductase, XO, either reversibly by oxidation of the sulfhydryl groups of two conserved cysteine residues. Under physiological conditions the XDH form appears to dominate with 80% over the XO form with 20%
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during inflammatory conditions, reversible oxidation of critical cysteine residues or limited proteolysis converts xanthine dehydrogenase, XDH, EC 1.17.1.4, to xanthine oxidase, XO, which reduces O2 to superoxide and H2O2. Conversion to XO, however, is not requisite for reactive oxygen species production, as XDH displays partial oxidase activity. Xanthine oxidoreductase generates proinflammatory oxidants and secondary nitrating species, with inhibition of XOR proving beneficial in a variety of disorders
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xanthine oxidase inhibition in small intestine ischemia-reperfusion injury leads to reduction in neutrophil infiltration
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enzyme inhibitors exert beneficial effect on endothelial dysfunction, mechanisms, overview, mechanism of action in cardiovascular disease, overview
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phosphatidylinositol 3-kinase and xanthine oxidase regulate nitric oxide and reactive oxygen species productions by apoptotic lymphocyte microparticles in endothelial cells, overview
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the enzyme activity, but not oxidative damage parameters, at the time of sepsis diagnosis is significantly higher in non-survival septic patients than in survival patients, overview
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the enzyme and its superoxide producing activity are involved in endothelial dysfunction in atherosclerosis, overview
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the enzyme catalyzes the oxidation of endogenous and exogenous purines and pyrimidines
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the enzyme is induced by heat shock, the reactive oxygen species produced by heat shock may play an important role in the heat shock-induced activation of MAPKs, which can induce MMP-1 and-9 expressions, overview
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the enzyme interacts with the Toll-like receptor-4, TLR-4, inducing proinflammatory cytokine production, extracellular superoxide production by the enzyme leads to nuclear translocation of nuclear factor-kappaB and increased neutrophil production of the NFkappaB-dependent cytokines tumor necrosis factor-alpha and macrophage inhibitory protein-2 mediated by TLR-4, overview
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the enzyme is capable to generate superoxide radicals and H2O2 derived from it, the synthesis of the radicals is increased upon a temperature shift from 30°C to 45°C and by photosensitization of tumor cells with a hematoporphyrin derivative, overview
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the enzyme, together with mitochondrial complex III, is responsible for reactive oygen species production in ischemic muscle, they act in tissue damage after ischemic-reperfusion, regulation, overview
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xanthine oxidase inhibition in small intestine ischemia-reperfusion injury leads to prevention of intestine necrosis
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chronic enzyme inhibition by allopurinol or febuxostat cannot prevent or treat the progression of congestive heart failure induced by coronary artery ligation in rabbits, overview
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xanthine oxidase is necessary during the physiological involution of tissues
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enzyme inhibitors exert beneficial effect on endothelial dysfunction, mechanisms, overview, mechanism of action in cardiovascular disease, overview
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xanthine oxidase inhibition in small intestine ischemia-reperfusion injury leads to reduction in villar necrosis, reduced intestinal MPO levels, reduced circulating neutrophil priming and reduction in pulmonary damage, prevention of permeability changes in intestinal mucosa, reduction in length of necrotic small bowel by 60%, reduction in intestinal apoptosis and tissue MDA levels; reduction in plasma MDA levels and improvement in renal function, and improved small intestine anastomotic healing and animal survival, overview
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xanthine oxidase-derived reactive oxygen species contribute to the development of D-galactosamine-induced liver injury in rats, overview
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enzyme inhibition by orange juice and hesperetin participates in preventing oxidative stress by enhancing total antioxidant capacity and decreasing lipid peroxidation, overview
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
[2Fe-2S] cluster
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two N-terminal non-identical iron-sulfur clusters of the [2Fe-2S]-type
FAD
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flavoprotein
392993, 393001, 393008, 644555, 644564, 644622, 644624, 644627, 644629, 644632, 644635, 644640, 644641, 644642, 644643, 644644, 644645, 644646, 644648, 644649, 644650, 644651, 644653, 644654, 644655, 644657
FAD
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required for reoxidation of the enzyme, contains two non-identical [2Fe-2S] centers
FAD
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the FAD cofactor is open to solvent in XO, but much less accessible in XDH, binding site structure, overview
FAD
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the FAD cofactor is open to solvent in XO, but much less accessible in XDH, binding site structure, overview
FAD
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XOR is a molybdoflavin protein, is not affected by inhibitor nitro-oleic acid
FAD
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the Mo(VI) ion at the active site is reduced to Mo(IV), which then transfers two electrons, via the 2Fe-2S clusters, to the FAD cofactor
molybdopterin
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one cofactor per subunit, oxidation of xanthine takes place at this center, electrons are rapidly distributed to the other centers by intramolecular electron transfer
[2Fe-2S]-center
two nonidentical [2Fe-2S] clusters designated as Fe/SI and Fe/SII, distinguished by redox potential and EPR signal
additional information
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cofactor conformation, binding structure analysis and mechanism, overview
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additional information
cofactor conformation, binding structure analysis and mechanism, overview
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additional information
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the molybdenum center is located in a separate subunit from the Fe/S- and flavin-containing parts of the enzyme
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CoCl2
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increased activity of xanthine oxidase in cells exposed to CoCl2 and subsequent increase in reactive oxygen species derived from enzyme activity, which results in accumulation of hypoxia-inducible factor 1alpha. Blockade of enzyme activity by allopurinol, N-acetyl-L-cysteine or siRNA significantly attenuates expression of hypoxia-inducible factor 1alpha and thus the induction of genes such as erythropoietin and vascular endothelial growth factor
Cu2+
Fe2+
Iron
Mo
Mo4+
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the Mo(VI) ion at the active site is reduced to Mo(IV), which then transfers two electrons, via the 2Fe-2S clusters, to the FAD cofactor
Molybdenum
additional information
Cu2+
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Cu2+ either stimulates or inhibits xanthine oxidase activity, depending on metal concentration (inhibition above 0.7 mM) and pre-incubation length, the latter also determining the inhibition type. Cu2+-enzyme complex formation is characterized by modifications in xanthine oxidase electronic absorption bands, intrinsic fluorescence, and alpha-helical and beta-sheet content. Apparent dissociation constant values imply high- and low-affinity Cu2+ binding sites in the vicinity of the enzyme's reactive centers, Cu2+ binding to high-affinity sites causes alterations around xanthine oxidase molybdenum and flavin adenine dinucleotide centers, changes in secondary structure, and moderate activity inhibition, binding to low affinity sites causes alterations around all xanthine oxidase reactive centers including FeS, changes in tertiary structure as reflected by alterations in spectral properties, and drastic activity inhibition. Stimulation is attributed to transient stabilization of xanthine oxidase optimal conformation. Potential role of copper in the regulation of xanthine oxidase activity, binding kinetics, detailed overview
Fe2+
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xanthine oxidase dependent oxidation of ascorbate is markedly increased in presence of iron
Fe2+
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two 2Fe-2S clusters. The Mo(VI) ion at the active site is reduced to Mo(IV), which then transfers two electrons, via the 2Fe-2S clusters, to the FAD cofactor
Iron
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iron-molybdenum protein
Molybdenum
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molybdenum cofactor is a complex between molybdenum and molybdopterin (a 6-alkylpterin with 4-carbon side chain which has an enedithiol at carbon 1' and 2', a hydroxyl at carbon 3', and a terminal phosphate group)
Molybdenum
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an iron-molybdenum protein
Molybdenum
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nitrate reduction to nitrite as well as nitrite reduction to NO occurs at the molybdenum site
Molybdenum
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the enzyme accelerates reaction rate via base-catalyzed chemistry in which a Mo-OH group undertakes nucleophilic attack on the carbon center to be hydroxylated, with concomitant hydride transfer to a catalytically essential Mo=S group in the molybdenum coordination sphere. This chemistry appears to proceed via obligate two-electron chemistry rather than in individual steps to yield a reduced enzyme product complex with product coordinmated to the active site molybdenum by means of the newly introduced hydroxyl group in a sinple end-on fashion
Molybdenum
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the molybdenum center is a pyranopterin-MoVI-OS-OH. The pyranopterin cofactor is coordinated to the metall via an enedithiolate side chain, coordination geometry, overview
Molybdenum
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XOR is a molybdenum-containing enzyme. In the oxidized form of XORs, the Mo(VI) ion is in the center of a square-pyramidal geometry, coordinated by an oxo-ligand at the apical position and one hydroxo and one sulfido ligand at equatorial positions,3a in addition to the two vicinal sulfur ligands contributed by the pterin group, cofactor geometry, overview
Molybdenum
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an iron-molybdenum protein
Molybdenum
XOR is a molybdenum-containing enzyme. In the oxidized form of XORs, the Mo(VI) ion is in the center of a square-pyramidal geometry, coordinated by an oxo-ligand at the apical position and one hydroxo and one sulfido ligand at equatorial positions, in addition to the two vicinal sulfur ligands contributed by the pterin group, cofactor geometry, overview
additional information
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the molybdenum center is located in a separate subunit from the Fe/S- and flavin-containing parts of the enzyme
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-2,3-dihydro-4H-chromen-4-one
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a flavone compound from Selaginellaceae with antiviral activity
1-O-(4''-O-caffeoyl)-beta-glucopyranosyl-1,4-dihydroxy-2-(3',3'-dimethylallyl)benzene
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2,4-dichloro-6-(2-phenyl-5,6-dihydropyrazolo[1,5-c]quinazolin-5-yl)phenol
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2-(3,4-dihydroxy-5-methoxyphenyl)-5,7-dihydroxy-4H-chromen-4-one
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competitive, 50% inhibition at 0.00022 mM
2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one
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competitive, 50% inhibition at 0.00124 mM
2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-6-methoxy-4H-chromen-4-one
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competitive, 50% inhibition at 0.00019 mM; competitive, 50% inhibition at 0.00020 mM
2-(4-chlorophenyl)-5-(3,4-dimethoxyphenyl)-5,6-dihydropyrazolo[1,5-c]quinazoline
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2-amino-6-hydroxy-8-mercaptopurine
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mixed-type inhibition, the inhibitor specifically blocks the enzyme activity with the drug 6-mercaptopurine, but does affect activity with xanthine and hypoxanthine to a lesser extent, overview
2-amino-6-purine thiol
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competitive inhibitor, the inhibitor specifically blocks the enzyme activity with the drug 6-mercaptopurine, but does affect activity with xanthine and hypoxanthine to a lesser extent, overview
2-coumaric acid
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competitively inhibits the enzyme by binding to the active site, have a protective effect against reactive oxygen species in cells, structure-function relationship, computational molecular docking, overview
2-hydroxy-4-methoxy-6-[(E)-2-(4-methoxyphenyl)ethenyl]benzaldehyde
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a resveratrol derivative
2-hydroxy-6-methylpurine
interacts with Arg880 in both active sites of the nezyme dimer, binding structure, overview
2-hydroxy-6-[(E)-2-(4-hydroxyphenyl)ethenyl]-4-methoxybenzaldehyde
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a resveratrol derivative
2-methoxycinnamic acid
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competitively inhibits the enzyme by binding to the active site, have a protective effect against reactive oxygen species in cells, structure-function relationship, computational molecular docking, overview
2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid
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i.e. febuxostat, TEI-6720, or TMX-67, mixed-type inhibition of both the oxidized and reduced form of xanthine oxidase
3,4-di-O-caffeoylquinic acid methyl ester
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reversible inhibition, IC50: 0.0036 mM
3,4-dihydroxyphenyl dodecanoate
sigmoidal inhibition of superoxide anion formation