The Effect of High Ethanol Doses on Rates of Ethanol Oxidation in Rats. A Reassessment of Factors Controlling Rates of Ethanol Oxidation in vivo

Abstract

Ethanol was oxidized more slowly by rats given an ethanol dose of 5.1 g/kg than by rats given an ethanol dose of 1.4 g/kg. A positive correlation was found between [lactate]/[pyruvate] ratios and rates of ethanol oxidation. Acetaldehyde concentrations varied between rats but in some cases were high enough to influence rates of ethanol oxidation. Liver alcohol dehydrogenase levels were just sufficient to account for ethanol oxidation rates observed in vivo. Pre-administration of a large ethanol dose (6.5 g/kg) did not alter mean [lactate]/[pyruvate] ratios or ethanol oxidation rates during metabolism of test doses of 2.5 g/kg. Injection of pyruvate did not increase rates of ethanol oxidation. Results did not support suggestions that a high-Km ethanol oxidizing system played an important role in vivo, that increased rates of ethanol oxidation were induced by large, acute ethanol doses or that the rate of NADH reoxidation controlled rates of ethanol metabolism. Results supported evidence which indicated that the level of alcohol dehydrogenase was the major factor limiting rates of ethanol oxidation in vivo.