Fructose‑2,6‑bisphosphate is a regulator of both glycolysis and gluconeogenesis for the phosphofructokinase reaction of glycolysis and the fructose‑1,6‑bisphosphatase reaction of gluconeogenesis. In turn, the concentration of fructose‑2,6‑bisphosphate is regulated by many hormones, second messengers, and enzymes.

Activate glycolysis/Inhibit gluconeogenesis: Increased levels of fructose-2,6-bisphosphate, activation of PFK-2

Activate gluconeogenesis/Inhibit glycolysis: Increased levels of glucagon, Increased levels of cAMP, Activation of fructose-2,6-bisphosphatase (FBPase-2)

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Fructose‑2,6‑bisphosphate is a regulator of both glycolysis and gluconeogenesis for the phosphofructokinase reaction of glycolysis and the fructose‑1,6‑bisphosphatase reaction of gluconeogenesis. In turn, the concentration of fructose‑2,6‑bisphosphate is regulated by many hormones, second messengers, and enzymes. How do the following affect glycolysis and gluconeogenesis?

Explanation:

Fructose-2,6-bisphosphate is an allosteric effector for the enzymes phosphofructokinase-1 (PFK-1) and fructose-1,6-bisphosphatase (FBPase-1). It increases the affinity of PFK-1 for fructose-6-phosphate thereby activating glycolysis. However, it reduces the affinity of FBPase-1 for its substrate, fructose-1,6-bisphosphate thereby inhibiting gluconeogenesis.

Activation of phosphofructokinase-2 activates glycolysis and inhibits gluconeogenesis by catalyzing the phosphorylation of fructose-6-phosphate to form fructose-2,6-bisphosphate.

Increased levels of glucagon stimulates the synthesis of cAMpP which activates cAMP-dependent ptrotein kinase which phosphorylates the bifunctional enzyme PFK-2/FBPase-2. The phosphorylation of this enzyme inhibits its PFK-2 activity and activates its FBPase-2 activity. This results in the activation of gluconeogenesis and inhibition of glycolysis.

Fructose-2,6-bisphosphatase breaks down fructose-2,6-bisphosphate to fructose-6-phospshate and a phosphoryl group. This results in the activation of gluconeogenesis and the inhibition of glycolysis.

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