ACETYLCARNITINE-MEDIATED INHIBITION OF ETHANOL OXIDATION IN HEPATOCYTES

Carnitine-mediated prevention of ethanol-induced hepatic steatosis is related to the attenuation of ethanol metabolism by carnitine in the i ntact rat. Although carnitine retards ethanol oxidation in the intact animal, the in vitro activities of ethanol-metabolizing enzymes remain unaltered. Therefore, hepatocytes were targeted to understand the mec hanism of carnitine effect on ethanol metabolism. Rat hepatocytes were isolated by a collagenase-perfusion technique and incubated in albumi n-containing medium with ethanol in the presence or absence of added c arnitine or related compounds. Ethanol oxidation was determined by the loss of ethanol as well as by the products formed. The rate of ethano l oxidation in the presence of carnitine was one-half the rate in the absence of carnitine (14 vs. 25 nmol . min(-1). million(-1) cells). It took 100 times the concentration of carnitine to equal the maximal in hibition produced by acetylcarnitine and the effect of acetylcarnitine was without a lag time. It is concluded that acetylcarnitine is the m ediator of carnitine inhibition of ethanol oxidation.