Xanthine oxidase

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. This enzyme plays an important role in the catabolism of purines in some species, including humans.

Reaction

* hypoxanthine + O2 + H2O ↔ xanthine + H2O2
* xanthine + O2 + H2O ↔ 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.

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 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.

ee also

* Allopurinol
* sodium molybdate

References

*

*

*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

*


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Look at other dictionaries:

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