The effects of high ethanol doses on rates of ethanol oxidation in rats. A reassessment of factors controlling rates of ethanol oxidation in vivo.

1. Ethanol was oxidised more slowly by rats which were given an ethanol dose of 5.1 g/kg than by rats which were given an ethanol dose of 1.4 g/kg. 2. A positive correlation was found between [lactate]/[pyruvate] ratios and rates of ethanol oxidation. 3. Acetaldehyde concentrations varied widely between rats, but in some cases were high enough to influence rates of ethanol oxidation. 4. Liver alcohol dehydrogenase levels were just sufficient to account for ethanol oxidation rates observed in vivo. 5. 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. 6. Injection of pyruvate did not increase rates of ethanol oxidation. 7. The results do not support suggestions that a high-Km ethanol oxidising system plays an important role in vivo, that increased rates of ethanol oxidation can be induced by large, acute ethanol doses or that the rate of NADH reoxidation controls rates of ethanol metabolism. 8. The results support other evidence which has indicated that the level of alcohol dehydrogenase is the major factor limiting rates of ethanol oxidation in vivo.