Study of the fructose 6-phosphate/fructose 1,6-bi-phosphate cycle in the liver in vivo.

1. The method proposed by Rognstad & Katz [(1976) Arch, Biochem, Biophys, 177, 337-345] for the determination of the fructose 6-phosphate/fructose 1,6-bisphosphate cycle by the randomization of carbon between C-1 and C-6 of glucose glucose formed from [1-14C] galactose was applied to anaesthetized rats and conscious mice. 2. It was checked that the hydrolysis of fructose 6-phosphate by glucose 6-phosphatase is too weak to invalidate the method. The participation of the Cori cycle in the randomization was negligible within the short experimental period used (2-4 min). 3. No detectable randomization of carbon was observed in starved animals, indicating that phosphofructokinase is inactive in this experimental condition. 4. Randomization of carbon was detected as soon as 1 min after administration of [1-14C] galactose to fed animals and was maximal at about 3-4 min. It was calculated that on average 15% of the glucose formed by the liver to fed rats was recycled through the triose phosphates. The extent of cycling was quite variable. Recycling was also observed in starved rats in which glucose had been administered intravenously 10 min previously. In these animals, recycling was completely inhibited by glucagon. 5. The main factors that appear to be responsible for the very large changes in recycling observed in various experimental conditions are the concentrations of fructose 1,6-bisphosphate and of fructose 6-phosphate and also the affinity of phosphofructokinase for fructose 6-phosphate. The concentration of nucleotides does not seem to play a role.