Ethanol and hepatic protein turnover.

Acute and chronic effects of ethanol on three pathways of hepatic protein turnover, synthesis, secretion and degradation, are reviewed and their contribution to ethanol-induced protein accumulation are discussed. In several studies it has been shown that acute dose of ethanol does not change the rate of protein synthesis in vivo, while in vitro inhibition is generally found. The reported effects of chronic ethanol treatment are more variable, since increased, unchanged and inhibited rates of protein synthesis has been measured. Thus further research is needed to clarify the role of protein synthesis in ethanol-induced accumulation of hepatocellular protein. Secretion of plasma proteins decreases both after acute and chronic administration of ethanol due to inhibition of synthesis, glycosylation and exocytosis. Although inhibition of glycosylation and exocytosis cause retention of export proteins in the liver and thus increase hepatic protein, no single plasma protein has been found to accumulate inside the hepatocyte in large amounts. This can be explained by rapid lysosomal degradation of nonsecreted plasma proteins in the hepatocyte. Acute as well as chronic ethanol treatment inhibit lysosomal protein degradation suggesting that resident proteins play an important role in the ethanol-induced accumulation of protein. Taken together, it is evident that the effect of ethanol on protein metabolism is multifunctional and the ethanol-induced changes in synthesis, secretion and degradation of proteins contribute either positively or negatively to the increase in hepatic protein mass that is frequently observed after chronic ethanol treatment.