Factors influencing rates of ethanol oxidation in isolated rat hepatocytes

The stimulation of ethanol oxidation by fructose which has frequently been observed in isolated hepatocytes was found to occur only in unsupplemented cells. In the presence of other substrates (lactate, pyruvate) which accelerate ethanol oxidation, fructose had no additional effect. Acceleration of ethanol oxidation by fructose was not directly related to the ATP demand created by fructose. The effects of fructose on ethanol oxidation rates were not due to changes in acetaldehyde concentration. In cells from fed animals, acetaldehyde concentrations rose as high as 200 microM in some incubations, and therefore became a significant factor limiting ethanol oxidation rates. In hepatocytes isolated from starved rats incubated with pyruvate, where acetaldehyde concentrations were very low, (1-2 microM) it was possible to assess the effect of changes in [lactate]/[pyruvate] (and hence free cytosolic NADH) on rates of ethanol oxidation. The results showed that the increase in free cytosolic [NADH] usually found during ethanol oxidation in vivo would inhibit rates of ethanol clearance by a maximum of 20%.