NADH oxidase activity of rat liver xanthine dehydrogenase and xanthine oxidase-contribution for damage mechanisms.
The involvement of xanthine oxidase (XO) in some reactive oxygen species (ROS) -mediated diseases has been proposed as a result of the generation of O*- and H2O2 during hypoxanthine and xanthine oxidation. In this study, it was shown that purified rat liver XO and xanthine dehydrogenase (XD) catalyse the NADH oxidation, generating O*- and inducing the peroxidation of liposomes, in a NADH and enzyme concentration-dependent manner. Comparatively to equimolar concentrations of xanthine, a higher peroxidation extent is observed in the presence of NADH. In addition, the peroxidation extent induced by XD is higher than that observed with XO. The in vivo-predominant dehydrogenase is, therefore, intrinsically efficient at generating ROS, without requiring the conversion to XO. Our results suggest that, in those pathological conditions where an increase on NADH concentration occurs, the NADH oxidation catalysed by XD may constitute an important pathway for ROS-mediated tissue injuries.
Maia
Luisa
L
Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016, Lisboa, Portugal.
Vala
Andrea
A
Mira
Lurdes
L
D042931:Aldehyde Oxidase / Q000378:metabolism; D000818:Animals; D045304:Cytochromes c; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008081:Liposomes; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D019820:Xanthine / Q000378:metabolism; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D008081:Liposomes; D009097:Multienzyme Complexes; D017382:Reactive Oxygen Species; D019820:Xanthine; D008315:Malondialdehyde; D045304:Cytochromes c; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D042931:Aldehyde Oxidase; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D010100:Oxygen