Effects of superoxide dismutase and catalase during reduction of adrenochrome by DT-diaphorase and NADPH-cytochrome P450 reductase.
NADPH-cytochrome1 P450 reductase and DT-diaphorase catalyze and one- and two-electron reduction of adrenochrome to its o-semiquinone and o-hydroquinone, respectively. Under aerobic conditions both adrenochrome o-semiquinone and o-hydroquinone proved to be unstable, undergoing autoxidation with concomitant oxygen consumption and continuous NADPH and NADH oxidation. Molecular oxygen was found to play a predominant role in autoxidation of o-semiquinone during reduction of adrenochrome catalyzed by NADPH-cytochrome P450 reductase. In addition, molecular oxygen, in the presence of manganese, was found to be responsible for the majority of autoxidation of o-semiquinone. However, the role of superoxide radicals in the autoxidation of leucoadrenochrome during the reduction of adrenochrome by DT-diaphorase was found to be predominant. Catalase different significantly with respect to NADPH and NADH oxidation during reduction of adrenochrome catalyzed by NADPH-cytochrome P450 reductase and DT-diaphorase. Catalase increased NADPH oxidation slightly, while NADH oxidation was inhibited during reduction of adrenochrome by NADPH cytochrome P450 reductase and DT-diaphorase, respectively. The presence of manganese in the incubation mixture was found to increase the prooxidant role of catalase on autoxidation during one-electron reduction of aminochrome catalyzed by NADPH cytochrome P450 reductase. A marked difference in the inhibitory effect of superoxide dismutase on oxygen consumption during adrenochrome reduction catalyzed by NADPH-cytochrome P450 reductase and DT-diaphorase was also observed. A possible mechanism for reduction of adrenochrome by NADPH-cytochrome P450 reductase and DT-diaphorase and a role for superoxide dismutase and catalase are proposed.
Baez
S
S
Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden.
Segura-Aguilar
J
J
D000323:Adrenochrome / Q000378:metabolism*; D000818:Animals; D002374:Catalase / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004837:Epinephrine / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000502:physiology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism*
D008345:Manganese; D000323:Adrenochrome; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D009251:NADPH-Ferrihemoprotein Reductase; D016660:NAD(P)H Dehydrogenase (Quinone); D004837:Epinephrine