Acute effects of ethanol on hepatic protein synthesis and secretion in the rat

Abstract

In isolated hepatocytes, 6–50 mM ethanol inhibited the incorporation of amino acids into protein. These in vitro effects of ethanol were associated with greater increases in lactate/pyruvate ratios, slower rates of ethanol oxidation, and smaller acetaldehyde concentrations than those found in vivo. When the redox changes produced by ethanol were decreased by the addition of 4-methylpyrazole (an inhibitor of alcohol dehydrogenase), methylene blue (a scavenger of reducing equivalents) or a combination of aspartate and α-ketoglutarate (which provides substrates for the translocation of reducing equivalents from the cytosol into the mitochondria), the ethanol-induced inhibition of protein synthesis was prevented. This effect took place despite marked elevations of the acetaldehyde concentration after the addition of either methylene blue or aspartate plus α-ketoglutarate. When hepatocytes were isolated from rats fed alcohol-containing diets and incubated with ethanol, the redox changes were attenuated and ethanol failed to inhibit protein synthesis. Acute ethanol administration to rats decreased secretion of newly synthesized albumin with retention of albumin in the liver. This acute effect of ethanol on secretion was not associated with impairment of the synthesis of either albumin or total liver protein, as determined in vivo by the incorporation of [14C]leucine into proteins and the specific activity of leucyl-tRNA. Thus, acute ethanol administration inhibits hepatic protein secretion rather than protein synthesis. The inhibitory effect on protein synthesis produced by ethanol in vitro reflects the inability of isolated liver preparations to handle the excess of reducing equivalents generated by ethanol oxidation and does not correlate with acetaldehyde concentrations. The in vivo relevance of these in vitro effects remains to be determined.