Ethanol metabolism in isolated hepatocytes. Effects of methylene blue, cyanamide and penicillamine on the redox state of the bound coenzyme and on the substrate exchange at alcohol dehydrogenase.
Ethanol metabolism in hepatocytes increases the NADH/NAD+ ratio. The mechanism was investigated by measurements of the redox state of the coenzyme bound to alcohol dehydrogenase and of ethanol-acetaldehyde exchange and concomitant hydrogen transfer between ethanol molecules. Isolated hepatocytes from fed rats were incubated with cyclohexanone and cyclohexanol or with [1,1-2H2]-and [2,2,2-2H3]ethanol, followed by gas chromatographic determination of the redox state and isotope analysis of the ethanol by gas chromatography-mass spectrometry, respectively. Cyanamide and methylene blue decreased the redox shift caused by ethanol and increased the rates of acetaldehyde reduction during the exchange. Both drugs increased the extent of hydrogen transfer between ethanol molecules during oxidoreduction. Penicillamine had no significant effect on the ethanol-induced change in redox state of the bound coenzyme although it decreased the rate of acetaldehyde reduction. The results indicate that methylene blue inhibits aldehyde dehydrogenase and that accumulation of acetaldehyde decreases the redox effects of ethanol. The redox effect appears to result primarily from rapid elimination of acetaldehyde and equilibration with the NAD system on the alcohol dehydrogenase, but is not enhanced by further decreases in acetaldehyde concentration. Thus, penicillamine could probably be used to decrease the concentration of acetaldehyde without increasing the redox effects.
Cronholm
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Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden.
D000079:Acetaldehyde / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D003484:Cyanamide / Q000494:pharmacology*; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008751:Methylene Blue / Q000494:pharmacology*; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010396:Penicillamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009243:NAD; D000431:Ethanol; D003484:Cyanamide; D000426:Alcohol Dehydrogenase; D010396:Penicillamine; D000079:Acetaldehyde; D008751:Methylene Blue