Effect of ethanol metabolism on initiation of protein synthesis in rat hepatocytes

Rat liver parenchymal cells were incubated in the presence and absence of ethanol (80 mM). Polysomes were isolated and analysed on sucrose gradients. Ethanol was shown to inhibit the incorporation of 14C-valine into proteins, result in a shift in the distribution of polysomes towards smaller sizes, inhibit the formation of 40S initiation complexes, and diminish the concentration of glucose-6-phosphate in the hepatocytes. Addition of 4-methylpyrazole (0.5 mM) partially prevented the inhibition of protein synthesis and completely restored the polysomal distribution. It is concluded that ethanol inhibits protein synthesis partly by a mechanism linked to ethanol metabolism. This effect takes place at the level of initiation and may be mediated by a reduced gluconeogenesis.