Xanthine oxidase

Xanthine oxidase (XO (sometimes 'XAO'), a form of xanthine oxidoreductase that generates reactive oxygen species . 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.

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

Reaction
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. 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. 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.

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

Inhibitors
Inhibitors of XO include allopurinol, oxypurinol, and phytic acid.