The energy cost of the metabolism of drugs, including ethanol.

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Observations of changes in body weight in man and rats indicate that the administration of high doses of ethanol results in an inefficient utilization of calories. It is postulated that this is due, at least in part, to activation of energy wasteful metabolic pathways such as microsomal ethanol oxidizing system (MEOS) in the hepatic endoplasmic reticulum, that this effect is increased by microsomal enzyme proliferation induced by ethanol consumption, and that the energy balance may be similarly disturbed by administration of other drugs. The proposed mechanism for these changes is an increase in the microsomal oxidation of both substrates (such as ethanol) and of NADPH, a process which does not appear to be linked to energy conservation such as the production of ATP. In the case of ethanol, these effects would be expected to be most obvious during ingestion of moderately high doses because of the much higher Km of ethanol for MEOS than for ADH. Because of the ability of ethanol feeding to induce various microsomal enzyme activities, the metabolism of substrates other than ethanol may also be involved in the energy wasting process.