Cellular distribution, metabolism and regulation of the xanthine oxidoreductase enzyme system

Xanthine oxidase (EC 1.1.3.22) and xanthine dehydrogenase (EC 1.1.1.204) ar e both members of the molybdenum hydroxylase flavoprotein family and repres ent different forms of the same gene product. The two enzyme forms and thei r reactions are often referred to as xanthine oxidoreductase (XOR) activity . Physiologically, XOR is known as the rate-limiting enzyme in purine catab olism but has also been shown to be able to metabolize a number of other ph ysiological compounds. Recent studies have also demonstrated its ability to metabolize xenobiotics, including a number of anticancer compounds, to the ir active metabolites. During the past 10 years, evidence has mounted to su pport a role for XOR in the pathophysiology of inflammatory diseases and at herosclerosis as well as its previously determined role in ischemia-reperfu sion injury. While significant progress has recently been made in our under standing of the physiological and biochemical nature of this enzyme system, considerable work still needs to be done. This paper will review some of t he more recent work characterizing the interactions and the factors that in fluence the interactions of XOR with various physiological and xenobiotic c ompounds. (C) 2000 Elsevier Science Ireland Ltd. All lights reserved.