What does fructose 2,6-bisphosphate activate in glycolysis?

Fructose 2,6-bisphosphate is a crucial regulatory molecule in the glycolytic pathway, primarily functioning to activate phosphofructokinase-1 (PFK-1). PFK-1 is a key regulatory enzyme that catalyzes one of the rate-limiting steps of glycolysis, which converts fructose 6-phosphate to fructose 1,6-bisphosphate. The presence of fructose 2,6-bisphosphate increases the affinity of PFK-1 for its substrate and reduces the inhibitory effect of ATP, enabling glycolysis to proceed more effectively in conditions where energy is needed, such as during high energy demand or high levels of glucose.

This regulatory action is important because it allows the cell to finely tune the flow of glucose through glycolysis based on metabolic needs. In contrast, fructose 2,6-bisphosphate does not activate FBPase-1 (which acts in gluconeogenesis), pyruvate carboxylase, or pyruvate kinase, highlighting its specific role in enhancing glycolytic flux through the activation of PFK-1.