Differential Requirement for de novo RNA Synthesis in the Starved-refed Rat; Inhibition of the Overshoot by 8-Azaguanine after Refeeding

Abstract

The activities of phosphohexose isomerase, pyruvate kinase, L-α-glycerophosphate dehydrogenase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme, dihydroxyacetone kinase and hexose phosphorylating capacity were measured in ad libitum-fed rats, starved rats, and starved rats refed for 1, 2 and 3 days. The activities of all enzymes measured increased to about twice the level measured in rats adapted to ad libitum feeding on days 2 and 3 of refeeding, except the activity of L-α-glycerophosphate dehydrogenase and the hexose phosphorylating capacity, which after the overshoot at 2 days returned to normal levels 3 days after refeeding. Treatment with 8-azaguanine resulted in high levels of liver glycogen and prevented the overshoot in enzyme activities — but not the increase back to normal levels. Phosphorylase activity was the same in both treated and nontreated rats; thus, increased liver glycogen levels in rats treated with azaguanine could not be explained on the basis of phosphorylase activity. 8-Azaguanine did decrease food intake; however, the overshoot was also observed in pair-fed rats. Therefore, the absence of overshoot in azaguanine-treated rats was not due to a decrease in food intake. The observed overshoot in enzyme activities on day 2 of refeeding was not observed in rats which received the first injection of the antibiotic 12 hours after refeeding. A possible explanation of the data is that the overshoot observed after refeeding is dependent on de novo RNA synthesis which occurs at least 12 hours after refeeding.