A re-evaluation of the tissue distribution and physiology of xanthine oxidoreductase

Abstract

Xanthine oxidoreductase is an enzyme which has the unusual property that it can exist in a dehydrogenase form which uses NAD+ and an oxidase form which uses oxygen as electron acceptor. Both forms have a high affinity for hypoxanthine and xanthine as substrates. In addition, conversion of one form to the other may occur under different conditions. The exact function of the enzyme is still unknown but it seems to play a role in purine catabolism, detoxification of xenobiotics and antioxidant capacity by producing urate. The oxidase form produces reactive oxygen species and, therefore, the enzyme is thought to be involved in various pathological processes such as tissue injury due to ischaemia followed by reperfusion, but its role is still a matter of debate. The present review summarizes information that has become available about the enzyme. Interpretations of contradictory findings are presented in order to reduce confusion that still exists with respect to the role of this enzyme in physiology and pathology.

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“…First, xanthine oxidase activity is not likely to be the source of ROS in both liver and small intestine because neither allopurinol nor hypox- anthine resulted in a detectable effect. Moreover, the granular form of final reaction product was not indicative of a soluble enzyme, such as xanthine oxidase (Kooij, 1994). Secondly, the presence of NADP did not have any effect.…”

Protein Kinase A Catalytic Subunit Alters Cardiac Mitochondrial Redox State and Membrane Potential Via the Formation of Reactive Oxygen Species

“…There are several extra-mitochondrial sources of ROS and the assignment of the mitochondria as the site of ROS generation is not completely resolved. [29][30][31] We demonstrated that PKAcat induced ROS generation and Trolox inhibited PKAcat-induced ROS generation. Furthermore, PKAcatinduced ∆ m depolarization was also inhibited by another ROS scavenger, N-acetylcysteine (NAC; 400 mol/L, data not shown).…”

Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease

“…The hepatic localization of XOR is zonally distributed, with higher activity in pericentral, compared with periportal, hepatocytes (44). The zonal distribution of XOR corresponds to regions where ischemia and hypoxia would be most severe, as oxygen is extracted as blood flows from the portal triad to the central vein branches.…”