Review
Pathophysiology of circulating xanthine oxidoreductase: New emerging roles for a multi-tasking enzyme

https://doi.org/10.1016/j.bbadis.2014.05.022Get rights and content
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Highlights

  • During evolution mammalian XOR acquired the ability of generating oxidants.

  • The increase of XOR in serum has been shown in many pathological conditions.

  • XOR-derived ROS have a signal function with a pro-inflammatory action.

  • Circulating XOR is associated with pathologies depending on endothelial dysfunction.

  • XOR and uric acid in serum seem implicated in cardiovascular diseases.

Abstract

The enzyme xanthine oxidoreductase (XOR) catalyses the last step of purine degradation in the highest uricotelic primates as a rate-limiting enzyme in nucleic acid catabolism. Although XOR has been studied for more than a century, this enzyme continues to arouse interest because its involvement in many pathological conditions is not completely known. XOR is highly evolutionarily conserved; moreover, its activity is very versatile and tuneable at multiple-levels and generates both oxidant and anti-oxidant products. This review covers the basic information on XOR biology that is essential to understand its enzymatic role in human pathophysiology and provides a comprehensive catalogue of the experimental and human pathologies associated with increased serum XOR levels. The production of radical species by XOR oxidase activity has been intensively studied and evaluated in recent decades in conjunction with the cytotoxic consequences and tissue injuries of various pathological conditions. More recently, a role has emerged for the activity of endothelium-bound enzymes in inducing the vascular response to oxidative stress, which includes the regulation of pro-inflammatory and pro-thrombotic activities of endothelial cells. The possible physiological functions of circulating XOR and the products of its enzyme activity are presented here together with their implications in cardiovascular and metabolic diseases.

Abbreviations

de-Mo
demolybdo form
de-S
desulpho form
Mo
molybdenum
NO
nitric oxide
ROS
reactive oxygen species
RyR2
ryanodine receptor
XDH
xanthine dehydrogenase
XDH/XO
intermediate form
XO
xanthine oxidase
XOR
xanthine oxidoreductase
XOR
gene for XOR

Keywords

Cardiovascular diseases
Endothelium functions
Metabolic syndrome
Oxidative stress
Uric acid
Xanthine oxidoreductase

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