Xanthine oxidoreductase-catalyzed reactive species generation: A process in critical need of reevaluation
| Autor: | Nadiezhda Cantu-Medellin, Eric E. Kelley |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Xanthine oxidoreductase
Xanthine Dehydrogenase Nitrite Clinical Biochemistry I/R ischemia/reperfusion Free radicals Biochemistry GAGs glycosaminoglycans Nitric oxide chemistry.chemical_compound ROS reactive oxygen species medicine XOR xanthine oxidoreductase) Animals Humans Oxygen tension NOS nitric oxide synthase Hypoxia lcsh:QH301-705.5 •NO nitric oxide chemistry.chemical_classification Inflammation XO xanthine oxidase Reactive oxygen species lcsh:R5-920 biology Organic Chemistry Nitrite reductase medicine.disease Graphical Review XDH xanthine dehydrogenase Nitric oxide synthase chemistry Xanthine dehydrogenase lcsh:Biology (General) H2O2 hydrogen peroxide Biocatalysis biology.protein Reactive Oxygen Species lcsh:Medicine (General) Reperfusion injury O2•− superoxide |
| Zdroj: | Redox Biology, Vol 1, Iss 1, Pp 353-358 (2013) Redox Biology |
| ISSN: | 2213-2317 |
| Popis: | 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 nitrate/nitrite 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. Highlights • Inflammation-induced elevation of XO has long been associated with negative outcomes. • Yet, XO-derived reactive species generation is poorly understood leading to misconceptions. • For example, H2O2 and not O2•− is the major reactive product of XO. • And, recent reports demonstrate beneficial •NO production by XO and nitrite. • As such, a detailed reevaluation of XO-catalyzed reactive species generation is crucial. |
| Databáze: | OpenAIRE |
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