EFFECT OF FASTING ON THE ACTIVITY AND TURNOVER OF RAT-LIVER ALCOHOL-DEHYDROGENASE

Alcohol dehydrogenase activity in rat liver decreased with fasting to .apprx. 60% of the fed level, but the specific activities of the enzyme purified from livers of fed and 12 or 48 h fasted animals were similar, 3.2-3.4 U/mg protein. Therefore, the decrease in enzyme activity with fasting should have resulted from a decrease in the amount of enzyme protein. The turnover of alcohol dehydrogenase was examined in fed and fasted rats. The fractional rate of enzyme synthesis (ka) in fed rats was determined by radioisotopic methods to be 0.13 day-1 and it increased to 0.18 day-1 after a 12 or 48 h fast. The absolute rate of synthesis (V) and the fractional rate of degradation (kd) were calculated from these ks values, and the total enzyme content in livers from animals that were fasted for 8-72 h. After 48-72 h of fasting, V decreased 16% and kd increased .apprx. 20% with respect to the fed values. These changes accounted for the lowered enzyme activity in the fasted state. The rapid decrease in enzyme activity with fasting, t1/2 .simeq. 16 h, was due to a rapid increase in kd from 0.14-0.16 day-1 in fed animals to 0.61 day-1 during the first 8 h after the initiation of fast. Thereafter, kd decreased steadily to reach 0.18 day-1 after 48-72 h of fasting.