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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 Method¹

Department of Physiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616

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 (gluco-neogenic) 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.

KEY WORDS: • 6-phosphogluconate • fructose • 2,6-bisphosphate • phosphofructokinase • lipogenesis

¹ The work was supported by grant AM 28319 from the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases of the National Institutes of Health.

² Present address: The Howard Hughes Medical Institute, SL-15, University of Washington, Seattle, WA 98195.

Manuscript received 9 January 1984.