Fructose-2,6-P2, chemistry and biological function.
A new activator of phosphofructokinase, which is bound to the enzyme and released during its purification, has been discovered. Its structure has been determined as beta-D Fructose-2,6-P2 by chemical synthesis, analysis of various degradation products and NMR. D-Fructose-2,6-P2 is the most potent activator of phosphofructokinase and relieves inhibition of the enzyme by ATP and citrate. It lowers the Km for fructose-6-P from 6 mM to 0.1 mM. Fructose-6-P,2-kinase catalyzes the synthesis of fructose-2,6-P2 from fructose-6-P and ATP, and the enzyme has been partially purified. The degradation of fructose-2,6-P2 is catalyzed by fructose-2,6-bisphosphatase. Thus a metabolic cycle could occur between fructose-6-P and fructose-2,6-P2, which are catalyzed by these two opposing enzymes. The activities of these enzymes can be controlled by phosphorylation. Fructose-6-P,2-kinase is inactivated by phosphorylation catalyzed by either cAMP dependent protein kinase or phosphorylase kinase. The inactive, phospho-fructose-6,P,2-kinase is activated by dephosphorylation catalyzed by phosphorylase phosphatase. On the other hand, fructose-2,6-bisphosphatase is activated by phosphorylation catalyzed by cAMP dependent protein kinase. Investigation into the hormonal regulation of phosphofructokinase reveals that glucagon stimulates phosphorylation of phosphofructokinase which results in decreased affinity for fructose-2,6-P2 appears to be due to the decreased synthesis by inactivation of fructose-2,6-P2,2-kinase and increased degradation as a result of activation of fructose-2,6-bisphosphatase. Such a reciprocal change in these two enzymes has been demonstrated in the hepatocytes treated by glucagon and epinephrine. The implications of these observations in respect to possible coordinated controls of glycolysis and glycogen metabolism are discussed.
D004789:Enzyme Activation; D004837:Epinephrine / Q000502:physiology; D006597:Fructose-Bisphosphatase / Q000378:metabolism; D005635:Fructosediphosphates / Q000502:physiology; D005934:Glucagon / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006598:Hexosediphosphates / Q000502:physiology; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D010732:Phosphofructokinase-1 / Q000502:physiology*; D010766:Phosphorylation
D005635:Fructosediphosphates; D006598:Hexosediphosphates; D005934:Glucagon; D010732:Phosphofructokinase-1; D006597:Fructose-Bisphosphatase; D005947:Glucose; D004837:Epinephrine