The Fructose 1,6-Diphosphatase-Phosphofructokinase Substrate Cycle

Abstract

The effect of glucagon on the rate of gluconeogenesis from substrates not involving pathways of mitochondrial metabolism has been investigated in isolated rat liver cells. From estimation of the rates of glucose formation, glucose phosphorylation, fructose 6-phosphate phosphorylation, fructose 1,6-diphosphate dephosphorylation, and lactate and pyruvate formation, it is concluded that glucagon stimulates gluconeogenesis from galactose, dihydroxyacetone, xylitol, and fructose by influencing the rate of reactions involving fructose 6-phosphate. Both glucagon and cyclic adenosine 3′:5′-monophosphate act to inhibit flux through phosphofructokinase and enhance flux through fructose 1,6-diphosphatase. The simultaneous change produced by glucagon in expressed activity of each enzyme results in the redirection of carbon from lactate and pyruvate formation to glucose synthesis.