Metabolic correlates of ethanol, acetaldehyde, acetate and methanol in humans and animals.

Abstract

Following the administration of alcoholic beverages, ethanol exerts a number of direct and indirect effects on the body and in turn, ethanol is itself metabolized. Liver and brain are twomajor organs which are immediately concerned with the effects of ethanol. Ethanol acts as CNS depressant and as a source of energy. Since the metabolism of ethain the liver proceeds at a constant rate until completion,acetate is produced regardless of energy requirements of the body. Thus, ethanol plays the role of an aberrant nutrient. Although ethanol has no effect on oxygen consumption in the liver, it severely suppresses the productionof carbon dioxide in the Krebs cycle resulting in the corresponding suppressionof respiratory quotient. This indicates that ethanol diverts the utilizationof oxygen for the oxidationof reducing, equivalents which accumulate as a consequence of increased formation of NADH. This is reflected in the shift from the oxidative to reductive components of a number of oxido-reductive couples, e.g.: pyruvate-lactate, oxaloacetate-malate and acetoacetate-beta-hydroxybutyrate. These actions of ethanol are exarcerbated by the fact that the metabolism of ethanol is also associated with the diversion of the availability of a number of enzymes and coenzymes from the metabolism of endogenous substrates towards the metabolism of metabolites of ethanol, thus resulting in the competitive inhibitionof a number of enzyme catalyzed reactions, e.g., inhibition of methanol metabolism during long-term consumption resulting in the acumulation of methanol in body fluids; shift in the peripheral metabolism of biogenic amines from oxidative to reductive pathways; and formation of aberrant neurotransmitters (in vitro); inhibition of the oxidation of fatty acids in the liver...