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?

Glycolysis is stimulated by a high concentration of fructose-2,6-bisphosphate, and the gluconeogenesis is stimulated by a low concentration of fructose-2,6-bisphosphate.

Explanation: Fructose-2, 6-bisphosphate (F2, 6P) is an allosteric activator of the key enzyme in the glycolysis cycle, phosphofructokinase (PFK). F2, 6P also acts as an inhibitor of fructose bisphosphate phosphatase (FBPase) in gluconeogenesis. The concentration of F2, 6P is governed by the balance between its synthesis and breakdown, catalysed by phosphofructokinase-2 (PFK-2) and fructose-bisphosphatase-2 (FBPase-2), respectively. These enzymes are found in a dimeric protein and are controlled by a phosphorylation/dephosphorylation mechanisms. Phosphorylation of the dimeric protein results in an increased concentration of FBPase-2, leading to a decreased concentration of F2, 6P, thus activating the gluconeogenesis cycle. The concentration of PFK-2 is increased when the dephosphorylation of the dimeric protein takes place, leading to the increased concentration of F2, 6P, thus stimulating glycolysis cycle.

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