Concerted action of DT-diaphorase and superoxide dismutase in preventing redox cycling of naphthoquinones: an evaluation.
It has been suggested that the enzymes DT-diaphorase and superoxide dismutase act in concert to prevent redox cycling of naphthoquinones and thus protect against the toxic effects of such substances. Little is known, however, about the scope of this process or the conditions necessary for its operation. In the presence of low levels of DT-diaphorase, 2-methyl-1,4-naphthoquinone was found to undergo redox cycling. This was very effectively inhibited by SOD, and in the presence of both enzymes the hydroquinone was maintained in the reduced form. The inhibitory effect of the enzyme combination was overcome, however, at high concentrations of the quinone, or by small increases in pH. Furthermore, redox cycling was re-established by addition of haemoproteins such as cytochrome c and methaemoglobin. DT-diaphorase and SOD strongly inhibited redox cycling by 2,3-dimethyl- and 2,3-dimethoxy-1,4-naphthoquinone, but not that of 2-hydroxy-, 5-hydroxy- or 2-amino-1,4-naphthoquinone. Inhibition of redox cycling by a combination of DT-diaphorase and SOD is therefore not applicable to all naphthoquinone derivatives, and when it does occur, it may be overwhelmed at high quinone concentrations, and it may not operate under slightly alkaline conditions or in the presence of tissue components capable of initiating hydroquinone autoxidation.
Munday
R
R
AgResearch, Ruakura Agricultural Research Centre, Private Bag 3123, Hamilton, New Zealand. rex.munday@agresearch.co.nz
D000818:Animals; D002417:Cattle; D003574:Cytochrome c Group / Q000378:metabolism; D001728:Dicumarol / Q000737:chemistry / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008706:Methemoglobin / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D009285:Naphthoquinones / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism*; D013997:Time Factors; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
D003574:Cytochrome c Group; D006454:Hemoglobins; D009285:Naphthoquinones; D014812:Vitamin K; D001728:Dicumarol; D008706:Methemoglobin; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); D003576:Electron Transport Complex IV; D010100:Oxygen; C023885:menadiol