Changes in the subcellular distribution of metabolites due to ethanol oxidation in the perfused rat liver.

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 tenfold 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 data suggest that the malate-aspartate shuttle is triggered by a decrease in the cytosolic oxaloacetate concentration which, due to the cytosolic aspartate aminotransferase equilibrium, leads to an increased efflux of 2-oxoglutarate and aspartate from the mitochondria in exchange for malate and glutamate, respectively. The first site at which the citrate cycle is inhibited appears to be the level of 2-oxoglutarate oxidation.