Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.17.3.2

Official Name

xanthine oxidase

Name from literature

xanthine oxidase

Pathway from literature

nucleic acid degradation/purine catabolism

Pathway from KEGG

Nucleotide Metabolism; Purine metabolism; map00230

Xenobiotics Biodegradation and Metabolism; Drug metabolism - other enzymes; map00983

Biosynthesis of Secondary Metabolites; Caffeine metabolism; map00232

Organisms

Human (9606)

Genome localization

2p23.1[7498 ],

Comments

An iron-molybdenum flavoprotein (FAD) containing [2Fe-2S] centres. Also oxidizes hypoxanthine, some other purines and pterins, and aldehydes (i.e. possesses the activity of 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 enzyme from animal tissues can be converted into EC 1.17.1.4, xanthine dehydrogenase. That from liver exists in vivo mainly as the dehydrogenase form, but can be converted into the oxidase form by storage at -20 _degree_C, by treatment with proteolytic enzymes or with organic solvents, or by thiol reagents such as Cu2+, N-ethylmaleimide or 4-mercuribenzoate. The effect of thiol reagents can be reversed by thiols such as 1,4-dithioerythritol. EC 1.17.1.4 can also be converted into this enzyme by EC 1.8.4.7, enzyme-thiol transhydrogenase (glutathione-disulfide) in the presence of glutathione disulfide. The Micrococcus enzyme can use ferredoxin as acceptor.

Rate-limiting Description

"In cancer cells, the up-regulation of guanylate biosynthesis is amplified by the concurrent decrease in activities of the catabolic enzymes, nucleotidase, nucleoside phosphorylase, and the rate-limiting purine catabolic enzyme, xanthine oxidase." (1353938)

"The behavior of the rate-limiting enzyme of purine catabolism, xanthine oxidase (EC 1.2.3.2); was examined in normal liver, in 17 hepatomas of different growth rates, and in rapidly growing differentiating and regenerating liver." (187329)

Regulatory Information

Regulatory type

Detail

regulatory enzyme;

"The concept of a widely distributed and highly regulated enzyme capable of generating both ROS and NO is intriguing in both physiological and pathological contexts." (12208366)

key enzyme;

"Xanthine oxidase (XO) is a key enzyme which can catalyze xanthine to uric acid causing hyperuricemia in humans." (17379526)

transcriptional level;

"Transcriptional regulation of human xanthine dehydrogenase/xanthine oxidase." (9388548#8661045)

post translational modification;

"The enzyme purified from breast milk shows very low enzymatic activity, and it is suggested that human XOR has evolved so as to be regulated by an exceptional range of pre- and posttranslational mechanisms.#We observe that gene expression of XDH/XO is regulatory in a cell-specific manner and is markedly affected by inflammatory cytokines, steroids, and physiologic events such as hypoxia. Posttranslational processing is also important in regulating XDH/XO activity." (9788904#15237859)

inhibitor;

"The NAD+ dependent retinol oxidation catalyzed by xanthine dehydrogenase is strictly dependent on cellular retinol binding proteins and is inhibited by oxypurinol" (18569334)

phosphorylation;

P47989

phosphorylation;

P47989:from_uniprot:222_Phosphothreonine

Gene ontology

Gene ontology

GO:0050660 (F) FAD binding [P47989 ];
GO:0051537 (F) 2 iron, 2 sulfur cluster binding [P47989 ];
GO:0030151 (F) molybdenum ion binding [P47989 ];
GO:0005829 (C) cytosol [P47989 ];
GO:0005506 (F) iron ion binding [P47989 ];
GO:0004855 (F) xanthine oxidase activity [P47989 ];
GO:0009055 (F) electron carrier activity [P47989 ];
GO:0005777 (C) peroxisome [P47989 ];
GO:0004854 (F) xanthine dehydrogenase activity [P47989 ];
GO:0055114 (P) oxidation reduction [P47989 ];

Subcellular localization

Localization

peroxisome [P47989 ];

Disease relevance

Disease

May contribute to adult respiratory stress syndrome (ARDS) and may potentiate influenza infection through an oxygen metabolite-dependent mechanism [P47989 ];

Defects in XDH are the cause of xanthinuria type 1 (XU1) [MIM:278300]. Xanthinuria is characterized by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. XU1 is due to isolated xanthine dehydrogenase. XU1 patients can metabolize allopurinol [P47989 ];

Links

SwissProt

P47989

Entrez Gene

7498

HPRD

06363



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  Last Modified: 2009-03-24  
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