Effect of ethanol dose on amino acid and urea concentrations in the fed rat liver in vivo

Abstract

In order to assess the role of ethanol oxidation in vivo on amino acid metabolism and urea synthesis, the changes in the concentrations of hepatic dicarboxylic amino acids, glutamine, alanine, carbamoylphosphate and urea were measured in fed rats at various times after the administration of 10 and 50 mmoles of ethanol/kg body wt, i.p. (1) The dose dependence of the acute effects of ethanol upon liver dicarboxylic amino acids in vivo has been demonstrated. The 10 mmoles/kg ethanol dose determines an accumulation by 30 per cent of aspartate and glutamate in the rat liver (30 and 60 min after ethanol injection) whereas the 50 mmoles/kg ethanol dose induces a 35 per cent fall in the aspartate level at the same time, and only a 20 per cent increase in glutamate concentration during the second hour following ethanol injection. (2) The dose-dependent effects of ethanol upon the hepatic level of urea are also shown. A significant decrease by 20 per cent in the liver content of urea is only observed 60 min after the administration of the 50 mmoles/kg ethanol dose. (3) On the contrary, the ethanol induced alterations in the hepatic alanine and glutamine concentrations are not dose-dependent. A 50 per cent decrease in alanine level and a rise (about 30 per cent) in glutamine concentration are observed 30 and 60 min after the administration of the two ethanol doses. The comparison between the effects of either 10 or 50 mmoles/kg ethanol doses leads to the conclusion that the rate of ethanol oxidation related to the malate-aspartate shuttle activity is directly connected with the glutamate (and aspartate) concentration. These findings suggest that ethanol reduces the hepatic urea concentration in vivo only when the ethanol dose injected to rats induces a rapid decrease in the aspartate/glutamate ratio (about 40 per cent within 15 min following the injection of the 50 mmoles/kg ethanol dose).