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xanthine oxidase/dehydrogenase
Crystallographic structure (monomer) of bovine xanthine oxidase.[1]
The bounded FAD (red), FeS-cluster (orange), the molybdopterin cofactor with molybdenum (yellow) and salicylate (blue) are indicated.
EC number
CAS number 9002-17-9
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures
Gene Ontology AmiGO / EGO
xanthine oxidase/dehydrogenase
Symbol XDH
Entrez 7498
HUGO 12805
OMIM 607633
RefSeq NM_000379
UniProt P47989
Other data
EC number
Locus Chr. 2 p23.1

Xanthine oxidase (XO, a form of xanthine oxidoreductase that generates reactive oxygen species[2]) is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid. This enzyme plays an important role in the catabolism of purines in some species, including humans.[3][4]

Xanthine oxidase can be converted to xanthine dehydrogenase by reversible sulfhydryl oxidation.[5]



The following chemical reactions are catalyzed by xanthine oxidase:

  • hypoxanthine + H2O + O2 \rightleftharpoons xanthine + H2O2
  • xanthine + H2O + O2 \rightleftharpoons uric acid + H2O2

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.

Catalytic mechanism

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.[6] 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).

Clinical significance

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. 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.

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.

Inhibition of xanthine oxidase has been proposed as a mechanism for improving cardiovascular health.[7]

Both xanthine oxidase and xanthine oxidoreductase are also present in corneal epithelium and endothelium and may be involved in oxidative eye injury.[8]


Inhibitors of XO include allopurinol,[9] oxypurinol,[10] and phytic acid.[11]

See also


  1. ^ PDB 1FIQ; Enroth C, Eger BT, Okamoto K, Nishino T, Nishino T, Pai EF (September 2000). "Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion". Proc. Natl. Acad. Sci. U.S.A. 97 (20): 10723–8. doi:10.1073/pnas.97.20.10723. PMID 11005854. PMC 27090.  
  2. ^ Ardan T, Kovaceva J, Cejková J (2004). "Comparative histochemical and immunohistochemical study on xanthine oxidoreductase/xanthine oxidase in mammalian corneal epithelium". Acta Histochem 106 (1): 69–75. doi:10.1016/j.acthis.2003.08.001. PMID 15032331.  
  3. ^ Hille R (2005). "Molybdenum-containing hydroxylases". Arch. Biochem. Biophys. 433 (1): 107–16. doi:10.1016/ PMID 15581570.  
  4. ^ 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.  
  5. ^ "Entrez Gene: XDH xanthine dehydrogenase".  
  6. ^ Hille R. (2006). "Structure and Function of Xanthine Oxidoreductase". European Journal of Inorganic Chemistry 2006 (10): 1905–2095. doi:10.1002/ejic.200600087.  
  7. ^ Dawson J, Walters M (October 2006). "Uric acid and xanthine oxidase: future therapeutic targets in the prevention of cardiovascular disease?". British journal of clinical pharmacology 62: 633. doi:10.1111/j.1365-2125.2006.02785.x. PMID 17052251.  
  8. ^ Cejková J, Ardan T, Filipec M, Midelfart A (2002). "Xanthine oxidoreductase and xanthine oxidase in human cornea". Histol. Histopathol. 17 (3): 755–60. PMID 12168784.  
  9. ^ Pacher P, Nivorozhkin A, Szabó C (March 2006). "Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol". Pharmacol. Rev. 58 (1): 87–114. doi:10.1124/pr.58.1.6. PMID 16507884.  
  10. ^ Spector T (January 1988). "Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical". Biochem. Pharmacol. 37 (2): 349–52. doi:10.1016/0006-2952(88)90739-3. PMID 2829916.  
  11. ^ Muraoka S, Miura T (February 2004). "Inhibition of xanthine oxidase by phytic acid and its antioxidative action". Life Sci. 74 (13): 1691–700. doi:10.1016/j.lfs.2003.09.040. PMID 14738912.  

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