Effect of Chronic Ethanol Administration on Protein Catabolism in Rat Liver

Hepatic protein catabolism was measured in rats which were pair‐fed a liquid diet containing either ethanol or isocaloric maltose‐dextrin (control diet). Within 12 days after initiation of pair feeding, the level of total hepatic protein in ethanol‐fed rats was 26K higher than that in pair‐fed control rats. During this time interval, the catabolic rates of both short‐lived [³H]puromycin‐labeled proteins and long‐lived native [¹⁴C]bicarbonate‐labeled proteins were measured In the two groups of animals. The degradation rate of short‐lived [³H] puromycinyl proteins and peptides was the same in ethanol‐fed and pair‐fed control rats. However, the overall catabolic rate of long‐lived proteins in rats fed the ethanol liquid diet for 2‐10 days was 37‐40% lower than that in pair‐fed controls. This difference in protein turnover was not a general phenomenon, since the time‐dependent decay of [¹⁴C]proteins in the hepatic microsome fraction of ethanol‐fed rats was 33% slower than that in pair‐fed controls, but the apparent rate of cytosolic protein catabolism was the same in both groups of animals. The differences in protein turnover did not reflect quantitative changes in lysosomal proteases since the activities of four hepatic lysosomal cathepsins were unaffected by alcohol administration. When rats were subjected to longer periods of pair feeding (16‐25 days), the difference in overall hepatic protein catabolism between ethanol‐fed rats and their pair‐fed controls was considerably attenuated. Our findings indicate that during the early stages of pair‐feeding, animals consuming ethanol showed a slower rate of degradation of long‐lived hepatic proteins compared with pair‐fed control rats. Since a significant determinant of cellular protein content is the rate of protein degradation, the results suggest that the lower rate of protein catabolism in ethanol‐fed rats accounts for part of the net hepatic protein accumulation in these animals.