F26BP

F26BP stands for fructose-2,6-bisphosphate, a small phosphate sugar that acts as a potent allosteric regulator of carbohydrate metabolism. It is not an intermediate of glycolysis or gluconeogenesis itself, but modulates key enzymes to shift flux between these pathways. The molecule is produced from fructose-6-phosphate by the bifunctional enzyme phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/F2,6BPase), which adds a phosphate from ATP. The same enzyme can also degrade F26BP to fructose-6-phosphate via its phosphatase activity. The balance between kinase and phosphatase activities determines cellular F26BP levels.

F26BP exerts its metabolic effect by allosterically activating phosphofructokinase-1 (PFK-1), the rate-limiting step of glycolysis, and by inhibiting fructose-1,6-bisphosphatase, a key gluconeogenic enzyme. Thus high F26BP favors glycolysis; low F26BP favors gluconeogenesis. Hormonal signals regulate this balance through phosphorylation of the PFK-2/FBPase-2 enzyme: insulin signaling tends to raise F26BP in liver, promoting glycolysis, whereas glucagon and adrenaline decrease F26BP, steering metabolism toward glucose production.

F26BP is conserved across many organisms, including bacteria, yeast, plants, and animals. In vertebrates, a family of PFK-2/FBPase-2 bifunctional enzymes carries out its synthesis and degradation, often with tissue-specific expression and regulatory properties.

Because of its central role in metabolic control, F26BP is a focus of research into metabolic diseases such as diabetes and cancer metabolism, where altered F26BP signaling can redirect glucose utilization.