The Role of Disulfiram in Alcohol Metabolism and the Treatment of Alcoholism

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the two major enzymes responsible for the metabolism of ethanol. ADH converts ethanol to acetaldehyde and ALDH converts acetaldehyde to acetate. Disulfiram is an irreversible inhibitor of ALDH. The increase in serum aldehyde concentrations when alcohol is consumed in the presence of disulfiram produces acute, unpleasant symptoms known as the disulfiram-alcohol reaction. The mechanism of inhibition is believed to involve a disulfiram metabolite-cysteine adduct in the active pocket of ALDH.