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| {{enzyme
| | My name is Clifford and I am studying Continuing Education and Summer Sessions and Neuroscience at Boca Raton / United States.<br><br>Also visit my blog post; [http://irvinguuhv.jigsy.com San Antonio roofing contractor] |
| | Name = xanthine oxidase/dehydrogenase
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| | EC_number = 1.17.3.2
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| | IUBMB_EC_number = 1/17/3/2
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| | CAS_number= 9002-17-9
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| | GO_code = 0004855
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| | image = XanthineOxidase-1FIQ.png
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| | width =
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| | caption = Crystallographic structure (monomer) of bovine xanthine oxidase.<ref name="pmid11005854">{{PDB|1FIQ}}; {{cite journal | author = Enroth C, Eger BT, Okamoto K, Nishino T, Nishino T, Pai EF | title = Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 20 | pages = 10723–8 |date=September 2000 | pmid = 11005854 | pmc = 27090 | doi = 10.1073/pnas.97.20.10723| url =http://www.pnas.org/content/97/20/10723.abstract }}</ref><br>The bounded FAD (red), FeS-cluster (orange), the molybdopterin cofactor with molybdenum (yellow) and salicylate (blue) are indicated.
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| }}
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| {{infobox protein
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| | Name = xanthine oxidase/dehydrogenase
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| | caption =
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| | image =
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| | width =
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| | HGNCid = 12805
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| | Symbol = [[Xanthine dehydrogenase|XDH]]
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| | AltSymbols =
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| | EntrezGene = 7498
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| | OMIM = 607633
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| | RefSeq = NM_000379
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| | UniProt = P47989
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| | PDB = 1FIQ
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| | ECnumber = 1.17.3.2
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| | Chromosome = 2
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| | Arm = p
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| | Band = 23.1
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| | LocusSupplementaryData =
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| }}
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| '''Xanthine oxidase''' ('''XO''', sometimes 'XAO') is a form of '''[[xanthine oxidoreductase]]''', a type of [[enzyme]] that generates [[reactive oxygen species]].<ref>{{cite journal | author=Ardan T, Kovaceva J, Cejková J | title=Comparative histochemical and immunohistochemical study on xanthine oxidoreductase/xanthine oxidase in mammalian corneal epithelium | journal=Acta Histochem | volume=106 | issue=1 | year=2004 | pages=69–75 | doi=10.1016/j.acthis.2003.08.001 | pmid=15032331 }}</ref> These enzymes catalyze the [[oxidation]] of [[hypoxanthine]] to [[xanthine]] and can further catalyze the oxidation of xanthine to [[uric acid]]. These enzymes play an important role in the catabolism of purines in some species, including humans.<ref>{{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}}</ref><ref>{{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}}</ref>
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| Xanthine oxidase is defined as an ''enzyme activity'' (EC 1.17.3.2).<ref>{{cite web|url=http://www.genome.jp/dbget-bin/www_bget?ec:1.17.3.2|title=KEGG record for EC 1.17.3.2}}</ref> The same protein, which in humans has the [[HGNC]] approved gene symbol ''XDH'', can also have [[xanthine dehydrogenase]] activity (EC 1.17.1.4).<ref name="KEGG record for EC 1.17.1.4">{{cite web|url=http://www.genome.jp/dbget-bin/www_bget?ec:1.17.1.4|title=KEGG record for EC 1.17.1.4}}</ref> Most of the protein in the liver exists in a form with xanthine dehydrogenase activity, but it can be converted to xanthine oxidase by reversible sulfhydryl oxidation or by irreversible proteolytic modification.<ref name="entrez">{{cite web | title = Entrez Gene: XDH xanthine dehydrogenase| url =http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7498| accessdate = }}</ref><ref>{{cite web|url=http://www.omim.org/entry/607633?search=xanthine%20dehydrogenase&highlight=xanthine%20dehydrogenase|title=*607633 XANTHINE DEHYDROGENASE; XDH}}</ref>
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| ==Reaction==
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| The following chemical reactions are catalyzed by xanthine oxidase:
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| * hypoxanthine + H<sub>2</sub>O + O<sub>2</sub> <math>\rightleftharpoons</math> xanthine + H<sub>2</sub>O<sub>2</sub>
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| * xanthine + H<sub>2</sub>O + O<sub>2</sub> <math>\rightleftharpoons</math> uric acid + H<sub>2</sub>O<sub>2</sub>
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| * Xanthine oxidase can also act on certain other purines, pterins, and aldehydes. For example, it efficiently converts 1-methylxanthine (a metabolite of [[caffeine]]) to 1-methyluric acid, but has little activity on 3-methylxanthine.<ref>{{cite journal|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042732/pdf/bcp_0537.pdf|title=1-Methylxanthine derived from caffeine as a pharmacodynamic probe of oxypurinol effect|author=D. J. Birkett et al.|year=1997|journal=Br J Clin Pharmacol|volume=43|pages=197–200|pmc=2042732|pmid=9131954|issue=2}}</ref>
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| * Under some circumstances it can produce [[superoxide]] ion RH + H<sub>2</sub>O + 2 O<sub>2</sub> <math>\rightleftharpoons</math> ROH + 2 O<sub>2</sub><sup>−</sup> + 2 H<sup>+</sup>.<ref name="KEGG record for EC 1.17.1.4"/>
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| <gallery>
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| Image:Hypoxanthin - Hypoxanthine.svg|[[hypoxanthine]] (one oxygen atom)
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| Image:Xanthin - Xanthine.svg|[[xanthine]] (two oxygens)
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| Image:Harnsäure Ketoform.svg|[[uric acid]] (three oxygens)
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| </gallery>
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| ==Protein structure==
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| The protein is large, having a [[molecular weight]] of 270 kDa, and has 2 [[Flavin group|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.
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| ==Catalytic mechanism==
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| The active site of XO is composed of a molybdopterin unit with the molybdenum atom also coordinated by terminal oxygen ([[oxo ligand|oxo]]), sulfur atoms and a terminal [[hydroxide]].<ref>{{cite journal
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| | author = Hille R.
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| | title = Structure and Function of Xanthine Oxidoreductase
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| | journal= [[European Journal of Inorganic Chemistry]]
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| | year = 2006
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| | volume = 2006
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| | issue = 10
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| | pages= 1905–2095
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| | doi = 10.1002/ejic.200600087}}</ref> In the reaction with xanthine to form uric acid, an oxygen atom is transferred from molybdenum to xanthine, whereby several intermediates are assumed to be involved.<ref>{{cite journal
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| | author = Metz S, Thiel W.
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| | title = A Combined QM/MM Study on the Reductive Half-Reaction of Xanthine Oxidase: Substrate Orientation and Mechanism
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| | journal= [[Journal of the American Chemical Society]]
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| | year = 2009
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| | volume = 131
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| | issue = 41
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| | pages= 14885–158902
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| | doi = 10.1021/ja9045394
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| | pmid = 19788181}}</ref> 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>).
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| ==Clinical significance==
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| Xanthine oxidase is a [[superoxide]]-producing enzyme found normally in [[Serum (blood)|serum]] and the lungs, and its activity is increased during [[Influenza A virus|influenza A]] infection.<ref>http://www.colorado.edu/intphys/iphy3700/vitCHemila92.pdf</ref>
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| 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.{{citation needed|date=July 2012}}
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| 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]]. Since xanthine oxidase is involved in the metabolism of [[6-mercaptopurine]], caution should be taken before administering allopurinol and 6-mercaptopurine, or its prodrug [[azathioprine]], in conjunction.
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| [[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. Type I xanthinuria has been traced directly to mutations of the ''XDH'' gene which mediates xanthine oxidase activity. Type II xanthinuria may result from a failure of the mechanism which inserts sulfur into the active sites of xanthine oxidase and [[aldehyde oxidase]], a related enzyme with some overlapping activities (such as conversion of [[allopurinol]] to [[oxypurinol]].<ref>{{cite web|url=http://www.omim.org/entry/603592?search=type%20II%20xanthinuria&highlight=ii%20xanthinuria%20type|title=OMIM: Xanthinuria type II}}</ref>
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| Inhibition of xanthine oxidase has been proposed as a mechanism for improving cardiovascular health.<ref name="pmid21894646">{{cite journal |author=Dawson J, Walters M |title=Uric acid and xanthine oxidase: future therapeutic targets in the prevention of cardiovascular disease? |journal=British Journal of Clinical Pharmacology |volume= 62|issue= 6|pages= 633|date=October 2006 |pmid=21894646 |pmc=1885190 |doi=10.1111/j.1365-2125.2006.02785.x}}</ref>
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| Both xanthine oxidase and xanthine [[oxidoreductase]] are also present in [[cornea]]l epithelium and endothelium and may be involved in oxidative eye injury.<ref name="pmid12168784">{{cite journal |author=Cejková J, Ardan T, Filipec M, Midelfart A |title=Xanthine oxidoreductase and xanthine oxidase in human cornea |journal=[[Histol. Histopathol.]] |volume=17 |issue=3 |pages=755–60 |year=2002 |pmid=12168784 |doi= |url=http://www.hh.um.es/Abstracts/Vol_17/17_3/17_3_755.htm}}</ref>
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| ==Inhibitors==
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| {{main|Xanthine oxidase inhibitor}}
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| Inhibitors of XO include [[allopurinol]],<ref name="pmid16507884">{{cite journal | author = Pacher P, Nivorozhkin A, Szabó C | title = Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol | journal = Pharmacol. Rev. | volume = 58 | issue = 1 | pages = 87–114 |date=March 2006 | pmid = 16507884 | pmc = 2233605 | doi = 10.1124/pr.58.1.6 | url = }}</ref> [[oxypurinol]],<ref name="pmid2829916">{{cite journal | author = Spector T | title = Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical | journal = Biochem. Pharmacol. | volume = 37 | issue = 2 | pages = 349–52 |date=January 1988 | pmid = 2829916 | doi = 10.1016/0006-2952(88)90739-3 | url = }}</ref> and [[phytic acid]].<ref name="pmid14738912">{{cite journal | author = Muraoka S, Miura T | title = Inhibition of xanthine oxidase by phytic acid and its antioxidative action | journal = Life Sci. | volume = 74 | issue = 13 | pages = 1691–700 |date=February 2004 | pmid = 14738912 | doi = 10.1016/j.lfs.2003.09.040 | url = }}</ref>
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| ==See also==
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| * [[xanthine dehydrogenase]]
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| * [[sodium molybdate]]
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| * Homogenized milk and atherosclerosis
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| ==References==
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| {{reflist|2}}
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| ==External links==
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| * {{MeshName|Xanthine+Oxidase}}
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| {{Other oxidoreductases}}
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| {{Nucleotide metabolism}}
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| [[Category:EC 1.17.3]]
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| [[Category:Metalloproteins]]
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| [[Category:Molybdenum enzymes]]
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| [[Category:Iron-sulfur enzymes]]
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My name is Clifford and I am studying Continuing Education and Summer Sessions and Neuroscience at Boca Raton / United States.
Also visit my blog post; San Antonio roofing contractor