The Mechanism of the Fructose Effect on the Ethanol Metabolism of the Human Liver*

Abstract

Liver vein catheterization studies showed that the splanchnic elimination of ethanol was about 1. 5 mmoles/minute when ethanol was infused alone, and about 2. 7 mmoles/minute when it was infused together with fructose. The splanchnic blood flow, oxygen consumption, production of acetate, glucose and lactate, any pyruvate consumption were also signiiicantly increased. Comparison of these results with experiments in which the effect of fructose was studied alone indicates that ethanol breakdown modifies the splanchnic metabolism of fructose. Thus the formation of carbondioxide, lactate and pyruvate is decreased, and conversion to glucose, sorbitol and glycerol is enhanced. It is assumed that the alterations are caused by an increased ratio between the reduced and the oxidized form of nicotinamide adenine dinucleotide in the extramitochondrial cytoplasm of the liver cells. The experiments are in agreement with the concept that the fructose effect on ethanol metabolism is caused by a reaction between glyceraldehyde, formed from fructose, and the complex alcoholdehydrogenase- reduced nicotinamide adenine dinucleotide. This results in the production of glycerol and regeneration of the oxidized form of the complex. Dissociation of the complex, which is thought to be the limiting step of ethanol dehydrogenation under normal circumstances, is thus partially bypassed.