Mechanism of the Inhibition of Aldehyde Dehydrogenase in Vivo by Disulfiram and Diethyldithiocarbamate

Aldehyde dehydrogenase in rat liver mitochondria and supernatant fluid has been assayed by following the rate of NADH production from NAD and aldehyde. Although it is known that disulfiram is a much more potent inhibitor in vitro of aldehyde dehydrogenase than diethyldithiocarbamate, the administration of either compound to rats brings about a decrease in enzyme activity in the livers of such animals. Very similar dose-response curves are obtained if it is assumed that diethyldithiocarbamate undergoes reoxidation to disulfiram in vivo . The decrease and return of activity of the supernatant and mitochondrial enzymes after disulfiram administration are identical in time course. The return of activity can be blocked by cycloheximide. These results indicate that disulfiram is an irreversible inhibitor of aldehyde dehydrogenase in vivo .