Xanthine oxidase 97644 220091840 2008-06-18T06:41:37Z DOI bot 6652755 Citation maintenance. Initiated by [[User:Fconaway|Fconaway]]. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. [[Image:XanthineOxidase-1FIQ.png|thumb|Xanthine Oxidase]] The [[enzyme]] '''xanthine oxidase''', or '''XO''', (bovine milk enzyme is {{PDB|1FIQ}}, {{EC number|1.17.3.2}}) catalyzes the [[oxidation]] of [[hypoxanthine]] to [[xanthine]] and can further catalyze the oxidation of xanthine to [[uric acid]] ==Reaction== * hypoxanthine + O<sub>2</sub> + H<sub>2</sub>O ↔ xanthine + H<sub>2</sub>O<sub>2</sub> * xanthine + O<sub>2</sub> + H<sub>2</sub>O ↔ uric acid + H<sub>2</sub>O<sub>2</sub> <gallery> Image:Hypoxanthin - Hypoxanthine.svg|[[hypoxanthine]] (One oxygen) Image:Xanthin - Xanthine.svg|[[xanthine]] (Two oxygens) Image:Harnsäure Ketoform.svg|[[uric acid]] (Three oxygens. Diagram is rotated.) </gallery> ==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 cluster]]s and participate in electron transfer reactions. ==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 (biochemistry)|substrate]] by XO originates from water rather than from [[dioxygen]] (O<sub>2</sub>). ==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. ==See also== * [[Allopurinol]] * [[sodium molybdate]] ==References== * {{cite journal |author=Hille R |title=Molybdenum-containing hydroxylases |journal=Arch. Biochem. Biophys. |volume=433 |issue=1 |pages=107–16 |year=2005 |pmid=15581570 |doi=10.1016/j.abb.2004.08.012}} * {{cite journal |author=Harrison R |title=Structure and function of xanthine oxidoreductase: where are we now? |journal=Free Radic. Biol. Med. |volume=33 |issue=6 |pages=774–97 |year=2002 |pmid=12208366|doi=10.1016/S0891-5849(02)00956-5}} *{{cite journal | author = Hille R. | title = Structure and Function of Xanthine Oxidoreductase | journal= [[European Journal of Inorganic Chemistry]] | year = 2006 | volume = 2006 | issue = 10 | pages= 1905–2095 | doi = 10.1002/ejic.200600087}} ==External links== * {{MeshName|Xanthine+Oxidase}} [[Category:EC 1.17.3]] [[Category:Metalloproteins]] [[Category:Molybdenum compounds]] [[Category:Iron compounds]] {{1.17-enzyme-stub}} {{Other oxidoreductases}} {{Nucleotide metabolism}} [[de:Xanthinoxidase]] [[fr:Xanthine oxydase]] [[ru:Ксантиноксидаза]]