Changes in the Subcellular Distribution of Metabolites Due to Ethanol Oxidation in the Perfused Rat Liver

Abstract

The subcellular distribution of metabolites involved in the transfer of reducing equivalents across the mitochondrial membrane was studied in perfused livers from fed rats. A 10-fold increase in the flux rate of the malate-aspartate shuttle and the inhibition of the citrate cycle due to ethanol oxidation, were reflected by characteristic changes in the cytosolic and mitochondrial concentrations of malate, 2-oxoglutarate, aspartate, glutamate and citrate. The malate-aspartate shuttle was triggered by a decrease in the cytosolic oxaloacetate concentration which, due to the cytosolic aspartate aminotransferase equilibrium, led to an increased efflux of 2-oxoglutarate and aspartate from the mitochondria in exchange for malate and glutamate, respectively. The 1st site at which the citrate cycle was inhibited appeared to be the level of 2-oxoglutarate oxidation.