Hormonal Regulation of Phosphofructokinase by Fructose 2,6-bisphosphate

Phosphofructokinase catalyzes the reaction: Fructose-6-P + ATP → fructose 1, 6-P₂ + ADP. This reaction represents the first committed step in glycolysis in the metabolism of glucose and glycogen. This enzyme in all mammalian tissues is subject to control and is the key regulatory enzyme of glycolysis. Liver phosphofructokinase is inhibited by ATP and citrate and activated by AMP and fructose 1, 6-P₂. However, attempts to rationalize the regulation of phosphofructokinase in vivo based on the in vitro data have not been satisfactory. A calculation shows that the enzyme should be completely inactive in vivo due to strong inhibition by high concentration of ATP and a high Km for fructose-6-phosphate. It became clear that an alternate explanation must be found.