Induction of rat liver glucose-6-phosphate dehydrogenase and malic enzyme during blockage of glycogen accumulation.

Liver glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) and malic enzyme (ME, EC 1.1.1.40) activities were measured in rats that were starved for 2 days and then fed a high-glucose, adequate-protein diet for 3 days. During refeeding the rats were injected with thyroxine to block glycogen accumulations preceeding the enzyme "overshoot". The G6PD and ME "overshoot" at the end of refeeding was still evident in spite of a 90% reduction in the glycogen peak. The results showed that the glycogen accumulation prior to the enzyme "overshoot" was not obligatory to the subsequent rise in enzyme activity. The sequential accumulation/breakdown of liver glycogen (day 1 refeeding) followed by the accumulation of liver fat (day 2 of refeeding) are probably the result of the changes in enzymatic pathways available to deal with the inflow of excess glucose. Such dissociation of glycogen accumulation and G6PD and ME "overshoot" during starvation-refeeding makes it highly unlikely that either glucose or glucose-6-phosphate derived from glycogen would be the direct, primary inducer of G6PD or ME in rat liver.