The Role of Alcohol Metabolism in the Effect of Ethanol on Protein Synthesis in Isolated Rat Hepatocytes

Rat liver parenchymal cells were isolated and incubated for 1–2 hr in a buffered salt solution. The addition of increasing concentrations of ethanol (10–105 mM| to the suspensions was accompanied by a dose‐dependent reduction (5%‐60%) of 14C‐valine incorporation into medium and cell proteins. Ethanol metabolism by alcohol dehydrogenase (ADH) was maximal between 10 and 20 m/W ethanol and did not increase at higher ethanol concentrations. Four‐methylpyrazole (4‐MP) (0.5 m/W), which inhibited ADH. abolished the inhibitory effect of low concentrations of ethanol (8 m/W) on valine incorporation, while it could not prevent the. inhibition caused by higher concentrations of ethanol (16 and 65 m/W). D‐Penicillamine (2 and 4 m/W), which complexes acetaldehyde, did not influence the inhibitory effect of ethanol on valine incorporation into protein. Additions of acetate (5 and 10 m/W) or sorbitol (3.5 and 5 m/W) were not able to mimic the effect of ethanol, as neither could reduction of medium pH from 7.4 to 7.0. Propanol (6–32 m/W) as well as tertiary butanol (5 and 10 m/W) inhibited valine incorporation into protein in a dose‐dependent manner. When ethanol was added to hepatocytes prepared from animals fed ethanol for 6 wk, the same inhibition of valine incorporation into protein was found as for cells from previously untreated rats. It was concluded that the inhibition of valine incorporation into liver proteins, which previously has been shown to be due to reduced protein synthesis, may occur in two ways. Low concentrations of ethanol appear to exert its effect through ethanol metabolism, while probably a direct effect of ethanol (and other alcohols) becomes increasingly important as the alcohol concentration rises.