Effects of diets on concentrations of 6-phosphogluconate and fructose 2,6-bisphosphate in rat livers and an assay of fructose 2,6-bisphosphate with an improved method.

We determined the effects of diets that have different lipogenic potentials on hepatic concentrations of 6-phosphogluconate and fructose 2,6-bisphosphate, both of which activate hepatic phosphofructokinase. Diets high in carbohydrate increased concentrations of both effectors compared to a high protein (gluconeogenic) diet. The concentration of 6-phosphogluconate was associated with the lipogenic nature of the diet, and the range of its concentration matched that over which phosphofructokinase responds to 6-phosphogluconate in vitro. In contrast, the concentration of fructose of 2,6-bisphosphate was not associated with the lipogenic potential of the diets. Fructose 2,6-bisphosphate was either absent from liver or its concentration was 10- to 30-fold higher than the concentration that gives the maximal activation of phosphofructokinase in vitro. The results indicate that fructose 2,6-bisphosphate and 6-phosphogluconate have different roles in the regulation of phosphofructokinase. Fructose 2,6-bisphosphate may be involved in switching hepatic carbohydrate metabolism between gluconeogenesis and glycolysis, whereas changes in the concentration of 6-phosphogluconate may coordinate the disposition of glucose 6-phosphate between the oxidative branch of the hexosemonophosphate pathway and glycolysis. In the course of our studies, we improved an enzymatic assay for fructose 2,6-bisphosphate.