Glucose 1,6-Diphosphate Formation by Phosphoglucomutase in Mammalian Tissues

Abstract

Glucose 1,6-diphosphate concentrations in 10 mouse tissues were found to range from 70 to 80 pmoles per kg in brain and red blood cells to 7 to 10 pmoles per kg in testes and pancreas.There was no discernible correlation between levels of glucose 1,6-diphosphate and levels of glucose 6phosphate, uridine diphosphoglucose or phosphoglucomutase, or Michaelis constants of phosphoglucomutase for its coenzyme.Ischemia caused a rapid decrease in glucose 1,6diphosphate level in brain, whereas there was little or no effect of starvation on the level in liver, or of maximal electrical stimulation on the level in muscle.Evidence is presented to show that glucose 1,6-di-P in muscle can be synthesized by P-glucomutase itself from fructose-l ,6-di-P and glucose-6-P (or glucose-l-P).The rate of synthesis is only about 0.015 % of the mutase rate for glucose-l-P, but this would be sufficient to synthesize the glucose-l ,6&-P in mouse muscle in 3 min.The equilibrium constant is about 12 for (fructose-l ,6-di-P) (glucose-6-P):(fructose-6-P) (glucose-l ,6-di-P).In the 20 years since the discovery of glucose 1,6-diphosphate (1) and its role as coenzyme for phosphoglucomutase (2), there have been very few investigations of the level of this substance in tissues.By accident, it was discovered that in mouse brain there is as much glucose 1,6-diphosphate as there is glucose 6-phosphate or uridine diphosphoglucose.This has prompted further study of levels of this cofactor in brain.Ischemia causes a rapid fall in brain coenzyme levels.It therefore seemed possible that there might be more of the coenzyme than previously supposed in other tissues as well.Consequently, normal levels have been measured in eight other organs with precautions to prevent change during sample preparation.In brain, the degradation and synthesis of glucose-l, 6-