Effect of ethanol administration on the metabolism of ethanol in baboons

To determine the mechanism whereby alcohol consumption accelerates ethanol metabolism, baboons were fed a diet containing ethanol (50% of calories) or an isocaloric control diet for 2 to 7 years. In alcohol-fed animals, the rate of ethanol metabolism per kilogram of body weight was accelerated by 34% at 50 mM concentrations of blood ethanol and liver size (estimated radiologically) increased by 23%. However, the rate of ethanol metabolism per gram of liver was not significantly increased. There was a 35% decrease in alcohol dehydrogenase (ADH) activity expressed per gram of liver and a 19% decrease per kilogram of body weight. Furthermore, the mitochondrial capacity to handle reducing equivalents was strikingly decreased as assessed by the rate of oxygen consumption at state 3 with glutamate and by the decrease in the activities of NADH and glutamate dehydrogenases. Thus, both factors presumed to be rate limiting for the ADH pathway (ADH activity and NADH reoxidation) were found to be decreased after chronic alcohol feeding. Therefore, even taking the increased liver size into consideration, the ADH pathway could not account for the rate of ethanol metabolism. By contrast, it was found that the activity of the microsomal ethanol-oxidizing system increased significantly after chronic alcohol consumption (by 22% expressed per gram of liver and by 54% expressed per kilogram of body weight). There were no significant changes in the content of cytochrome P-450.(ABSTRACT TRUNCATED AT 250 WORDS)