ETHANOL INHIBITS ACETATE METABOLISM IN RAT HEPATOCYTES

The metabolism of acetate al concentrations of 1, 2.5, 5 and 10 mM was investigated in freshly isolated hepalocytes from 48 hr fasted, female rats:in the absence and presence of 10 mM ethanol. The maximal capacity for acetate metabolism was 0.85 mu mol/(10(8) cells . min). Ethanol caused a 20% decrease in the apparent V-max for acetate metabolism and an increase in the apparent K-m for acetate from 3.0 to 4.6 mM. At physiological concentration of acetate (similar to 1 mM) and in the absence of an inhibitory effect of ethanol, the capacity for acetate metabolism was 15-20% of the rate of acetate formation from ethanol and the inhibitory effect of ethanol further reduced it to 10-15%. The results thus explain the well-known but hitherto not understood fact that only a small fraction of acetate produced in the liver during ethanol oxidation is further metabolized by the liver, while the majority is exported for oxidation in other tissues. Finally, a new method for calculation of liver acetate uptake in the presence of ethanol is presented.