Effect of Fructose and Glyceraldehyde on Ethanol Metabolism in Human Liver and in Rat Liver

Abstract

The basic kinetic parameters, V and Km, have been determined for liver enzymes involved in the metabolism of fructose and ethanol in rats and man. Values, previously not reported, or which deviate significantly from those reported in the literature are as follows: The maximal activity of aldehyde dehydrogenase from human liver with acetaldehyde as substrate was determined as 43 μmol × min−1× g wet wt−1. The activity of NADP‐dependent alcohol dehydrogenase with ethanol as substrate both in rat liver and in human liver was very low. The presence of glycerate kinase (12 μmol × min−1× g wet wt−1) in human liver has been established. The Km‐value of human‐liver alcohol dehydrogenase (NAD) for d‐glyceraldehyde was determined as 80–90 mM compared to 8–10 mM for the rat liver enzyme. The NADP‐dependent alcohol dehydrogenase from human liver had a Km‐value for d‐glyceraldehyde of 2.5–3.3 mM. Glycerate kinase from human and rat liver had Km‐values for d‐glyceraldehyde of 2.5–3.0 mM and 0.03 mM, respectively. In slices of human liver the increase in ethanol‐oxidation rate caused by 11 mM fructose (‘the fructose effect’) or by 2 mM d‐glyceraldehyde was 76% and 56%, respectively. In rat‐liver slices the effect of D‐glyceraldehyde upon ethanol metabolism was inhibited 100% by rotenone. In the same experiments rotenone caused a 5001, inhibition of the basic ethanol oxidation rate and of the oxygen consumption. 10 mM pyruvate, in experiments with liver slices from fasted rats, caused a 90%, increase in the ethanol oxidation rate in the absence of CO2, but only a 20%, increase in the presence of CO2 CO2 in itself caused a 70%, increase in the unstimulated oxidation of ethanol. Kinetic considerations and results reported in this paper held together with results from other laboratories lead to the conclusion that the theories previously proposed for the effect of fructose, d‐glyceraldehyde or pyruvate upon ethanol metabolism are irreconcilable with the experimental results. A new hypothesis for the ‘fructose effect’ is proposed. Malate dehydrogenase, malic enzyme, pyruvate carboxylase and transfer of oxaloacetate from the mitochondrial to the extramitochondrial compartment constitute a mechanism by which transfer of hydrogen from NADH to NADP may take place, thus increasing the rate of removal of NADH from the cytoplasm. Copyright © 1972, Wiley Blackwell. All rights reserved