Regulation of the synthesis and degradation of fructose-2,6-bisphosphate in liver

The bifunctional PFK-2/FBPase-2 is controlled by reversible phosphorylation of a specific serine residue near the N-terminus of each subunit of the homodimeric protein.

In the unphosphorylated form, the 6-phosphofructo-2-kinase domain (K) is active, and fructose-2,6-bisphosphate (F2,6BP) is synthesized.

In the phosphorylated form, the fructose-2,6-bisphosphatase domain (B) is active, and F2,6BP is degraded.

Glucagon stimulates phosphorylation by activating cAMP-dependent protein kinase (PKA). Insulin and glucose (via xyulose-5-phosphate) stimulate dephosphorylation by activating a protein phosphatase.