In vitro co-metabolism of acetoacetate and ethanol in human hepatic mitochondrial and cytosolic fractions

Abstract

The rate of alcohol elimination is highly resistant to acceleration in vivo in well-nourished individuals. The acceleration of ethanol elimination may be achieved by providing the conditions in which the action of alcohol dehydrogenase is not delayed by the insufficiency of the oxidized NAD form. The aim of the study was to verify the theoretically assumed mechanism of accelerating alcohol elimination by administering excessive acetoacetate (Ac-Ac) in the experimental in vitro model. Ac-Ac forming the redox system with beta-hydroxybutyrate (beta-HBA) is the natural acceptor of excessive protons from ethanol oxidation. Ac-Ac and beta-HBA penetrate freely through the cell membranes and are easily assimilated energetic substrates. The examinations were performed using the hepatic homogenates (collected from the cadavers shortly after death) supplemented with ethanol and Ac-Ac. The ethanol levels were determined at 0, 15, 60, 90 and 150 min of the experiment. The findings showed that the equimolar addition of Ac-Ac resulted in a two- to three-fold increase in ethanol oxidation in hepatic homogenates. The biochemical system discussed above resembles the natural way of utilizing the excessive NADH, which is formed during ethanol combustion in chronic alcoholics. The results indicate that further investigations are necessary to assess the clinical importance of this metabolic system.