Ethanol inhibits acetate metabolism in rat hepatocytes

The metabolism of acetate at concentrations of 1, 2.5, 5 and 10 mM was investigated in freshly isolated hepatocytes from 48 hr fasted, female rats in the absence and presence of 10 mM ethanol. The maximal capacity for acetate metabolism was 0.85 mumol/(10(8) cells.min). Ethanol caused a 20% decrease in the apparent Vmax for acetate metabolism and an increase in the apparent Km for acetate from 3.0 to 4.6 mM. At physiological concentration of acetate (approximately 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.