The Good and the Bad: The Bifunctional Enzyme Xanthine Oxidoreductase in the Production of Reactive Oxygen Species

Abstract

Xanthine oxidoreductase (XOR) is a molybdoflavin enzyme which occurs in two forms; the reduced form known as xanthine dehydrogenase (XDH, EC 1.17.1.4) and the oxidised form known as xanthine oxidase (XO, EC 1.17.3.2). In humans, it is a 293 kDa homodimer which catalyses consecutive hydroxylation steps of purine degradation. The oxidised form of the enzyme produces hydrogen peroxide and superoxide (O2•−), both of which are reactive oxygen species (ROS) that can interact with several biomolecules producing adverse reactions. XOR can also produce nitric oxide, a cardiovascular protective molecule. Overproduction of nitric oxide results in the formation of the highly reactive peroxynitrite radical. XOR-produced ROS may provide protection against infection, while at the same time can also lead to inflammation, oncogenesis, brain injury and stroke. XOR is also involved in tumour lysis syndrome in chemotherapy patients as well in ischaemia-reperfusion injury, increasing the levels of ROS in the body. Consequently, the presence of XOR in blood can be used as a biomarker for a number of conditions including oxidative stress and cardiovascular disease.