Fructose-2,6-bisphosphatase isozyme 3 (PFKFB3)

Fructose-2,6-bisphosphatase isozyme 3 (PFKFB3) is a bifunctional enzyme containing both kinase (PFK-2) and phosphatase (FBPase-2) domains that regulates the cellular concentration of fructose 2,6-bisphosphate, a key signaling molecule for glycolysis and gluconeogenesis[3][4][5]. The kinase domain synthesizes fructose 2,6-bisphosphate from fructose 6-phosphate and ATP, while the phosphatase domain degrades it. This regulation is crucial for metabolic switching in response to hormonal and energetic cues. PFKFB3 is notable for high kinase activity relative to phosphatase activity, especially in rapidly proliferating cells such as cancer cells, and is under active investigation as a target for anticancer therapies due to its role in driving the "Warburg effect" (aerobic glycolysis)[2][5]. Structural studies show that alterations in key residues affect bisphosphatase activity and are important in the regulation of this isozyme[2].

Other names

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3PFK-2/FBPase-2 isozyme 3PFKFB3

Inhibition of kinase domain to block fructose 2,6-bisphosphate synthesis and suppress glycolysis, especially in proliferating cancer cells[5]