Xanthine oxidase

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The enzyme xanthine oxidase, or XO, (bovine milk enzyme is PDB 1FIQ, EC 1.17.3.2) catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid

Contents 1 Reaction 2 Protein structure 3 Active site and mechanism of xanthine oxidase 4 Xanthine oxidase and disease 5 See also 6 References 7 External links

[edit] Reaction

• hypoxanthine + O₂ + H₂O ↔ xanthine + H₂O₂
• xanthine + O₂ + H₂O ↔ uric acid + H₂O₂

hypoxanthine (One oxygen)

xanthine (Two oxygens)

uric acid (Three oxygens. Diagram is rotated.)

[edit] Protein structure

The protein is large, having a molecular weight of 270,000, and has 2 flavin molecules (bound as FAD), 2 molybdenum atoms, and 8 iron atoms bound per enzymatic unit. The molybdenum atoms are contained as molybdopterin cofactors and are the active sites of the enzyme. The iron atoms are part of [2Fe-2S] ferredoxin iron-sulfur clusters and participate in electron transfer reactions.

[edit] Active site and mechanism of xanthine oxidase

The active site of XO is composed of a molybdopterin unit with the molybdenum atom also coordinated by terminal oxygen (oxo), sulfur atoms and a terminal hydroxide. In the reaction with xanthine to form uric acid, an oxygen atom is transferred from molybdenum to xanthine. The reformation of the active molybdenum center occurs by the addition of water. Like other known molybdenum-containing oxidoreductases, the oxygen atom introduced to the substrate by XO originates from water rather than from dioxygen (O₂).

[edit] Xanthine oxidase and disease

In humans, xanthine oxidase is normally found in the liver and not free in the blood. During severe liver damage, xanthine oxidase is released into the blood, so a blood assay for XO is a way to determine if liver damage has happened. As well, because xanthine oxidase is a metabolic pathway for uric acid formation, the xanthine oxidase inhibitor allopurinol is used in the treatment of gout.

Xanthinuria is a rare genetic disorder where the lack of xanthine oxidase leads to high concentration of xanthine in blood and can cause health problems such as renal failure. There is no specific treatment, sufferers are advised by doctors to avoid foods high in purine and to maintain a high fluid intake.

[edit] See also

• Allopurinol
• sodium molybdate

[edit] References

• Hille R (2005). "Molybdenum-containing hydroxylases". Arch. Biochem. Biophys. 433 (1): 107-16. doi:10.1016/j.abb.2004.08.012. PMID 15581570. 

• Harrison R (2002). "Structure and function of xanthine oxidoreductase: where are we now?". Free Radic. Biol. Med. 33 (6): 774-97. doi:10.1016/S0891-5849(02)00956-5. PMID 12208366. 

• Hille R. (2006). "Structure and Function of Xanthine Oxidoreductase". European Journal of Inorganic Chemistry 2006 (10): 1905-2095. doi:10.1002/ejic.200600087. 

[edit] External links

• MeSH Xanthine+Oxidase

v • d • e Other oxidoreductases (EC 1.15-1.18) 1.15 - Acting on superoxide as acceptor Superoxide dismutase 1.16 - Oxidizing metal ions Ceruloplasmin 1.17 - Acting on CH or CH2 groups Xanthine oxidase - Ribonucleotide reductase 1.18 - Acting on iron-sulfur proteins as donors Nitrogenase

v • d • e Metabolism: amino acid metabolism - nucleotide enzymes Purine metabolism Anabolism R5P->IMP: Ribose-phosphate diphosphokinase - Amidophosphoribosyltransferase - Phosphoribosylglycinamide formyltransferase - AIR synthetase (FGAM cyclase) - Phosphoribosylaminoimidazole carboxylase - Phosphoribosylaminoimidazolesuccinocarboxamide synthase - IMP synthase IMP->AMP: Adenylosuccinate synthase - Adenylosuccinate lyase - reverse (AMP deaminase) IMP->GMP: IMP dehydrogenase - GMP synthase - reverse (GMP reductase) Nucleotide salvage Hypoxanthine-guanine phosphoribosyltransferase - Adenine phosphoribosyltransferase Catabolism Adenosine deaminase - Purine nucleoside phosphorylase - Guanine deaminase - Xanthine oxidase - Urate oxidase Pyrimidine metabolism Anabolism CAD (Carbamoyl phosphate synthase II, Aspartate carbamoyltransferase, Dihydroorotase) Dihydroorotate dehydrogenase - Orotidine 5'-phosphate decarboxylase/Uridine monophosphate synthetase CTP synthase Catabolism Dihydropyrimidine dehydrogenase - Dihydropyrimidinase/DPYS - Beta-ureidopropionase/UPB1 Deoxyribonucleotides Ribonucleotide reductase - Nucleoside-diphosphate kinase - DCMP deaminase - Thymidylate synthase - Dihydrofolate reductase see also disorders, intermediates