Xanthine oxidoreductase-catalyzed reactive species generation: A process in critical need of reevaluation

摘要

Nearly 30 years have passed since the discovery of xanthine oxidoreductase (XOR) as a critical source of reactive species in ischemia/reperfusion injury. Since then, numerous inflammatory disease processes have been associated with elevated {XOR} activity and allied reactive species formation solidifying the ideology that enhancement of {XOR} activity equates to negative clinical outcomes. However, recent evidence may shatter this paradigm by describing a nitrateitrite reductase capacity for {XOR} whereby {XOR} may be considered a crucial source of beneficial ?NO under ischemic/hypoxic/acidic conditions; settings similar to those that limit the functional capacity of nitric oxide synthase. Herein, we review XOR-catalyzed reactive species generation and identify key microenvironmental factors whose interplay impacts the identity of the reactive species (oxidants vs. ?NO) produced. In doing so, we redefine existing dogma and shed new light on an enzyme that has weathered the evolutionary process not as gadfly but a crucial component in the maintenance of homeostasis.