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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. This enzyme plays an important role in the catabolism of purines in some species, including humans.12
Contents |
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.) |
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.
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.3 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).
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.
Inhibition of xanthine oxidase has been proposed as a mechanism for improving cardiovascular health.4
Inhibitors
Inhibitors of XO include allopurinolcitation needed, Oxypurinol, and phytic acid.5
See also
References
- ^ Hille R (2005). "Molybdenum-containing hydroxylases". Arch. Biochem. Biophys. 433 (1): 107–16. doi:. PMID 15581570.
- ^ Harrison R (2002). "Structure and function of xanthine oxidoreductase: where are we now?". Free Radic. Biol. Med. 33 (6): 774–97. doi:. PMID 12208366.
- ^ Hille R. (2006). "Structure and Function of Xanthine Oxidoreductase". European Journal of Inorganic Chemistry 2006 (10): 1905–2095. doi:.
- ^ 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. doi:. PMID 17052251. PMC: 1885190, http://dx.doi.org/10.1111/j.1365-2125.2006.02785.x.
- ^ Muraoka S, Miura T (February 2004). "Inhibition of xanthine oxidase by phytic acid and its antioxidative action". Life sciences 74 (13): 1691–700. PMID 14738912, http://linkinghub.elsevier.com/retrieve/pii/S0024320503010592.
External links
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