Increased alcohol dehydrogenase independent ethanol oxidation at high ethanol concentrations in isolated rat hepatocytes: the effect of chronic ethanol feeding

Abstract

Rates of ethanol oxidation in isolated rat hepatocytes increased with increasing ethanol concentrations even at near-saturation of the alcohol dehydrogenase (ADH) pathway. After inhibition of ADH by pyrazole, approximately 30% of ethanol-oxidizing activity remained and this activity of the non-ADH pathway was also dependent upon ethanol concentration. The apparent Km of th non-ADH pathway for ethanol was 13 mM, which is comparable to the value for the microsomal ethanol oxidizing system. Inhibition of catalase by azide affected the activity of the non-ADH pathway by less than 10%. After chronic ethanol feeding, the rates of ethanol oxidation in isolated hepatocytes and liver slices increased significantly compared to those in pair-fed controls. This adaptive increase of ethanol oxidation was more striking at a high ethanol level (30 mM) than at a low one (10 mM). Significant differences between the two groups remained even after inhibition of ADH and catalase. The results suggest that the microsomal ethanol oxidizing system may account for the major part of the non-ADH pathway.