PFK2 catalyzes formation of the compound fructose-2,6-bisphosphate (F2,6BP) by transferring a phosphate from ATP onto position 2 of fructose-6-phosphate (F6P) (Figure 16.7). F2,6BP is the most important allosteric regulator of glycolysis and gluconeogenesis and is formed as follows:
PFK2 is a single domain of an enzyme that also contains on it another domain for an enzymatic activity that reverses the effect of the PFK2-catalyzed reaction. The other domain is known as FBPase-2. FBPase-2 converts F2,6BP to F6P by hydrolyzing the phosphate at position 2 (liberating Pi), as follows:
(Note that this reaction is not the simple reversal of the PFK2-catalyzed reaction, but the F6P is regenerated.) Fructose-2,6-bisphosphatase is strongly inhibited by fructose-6-phosphate.
When the enzyme containing the PFK2 and FBPase-2 activities is phosphorylated by the cyclic-AMP-dependent protein kinase (cAPK), the FBPase-2 activity is favored and PFK-2 is inhibited. When the phosphate is removed, PFK2 activity is favored and FBPase-2 is inhibited.
Phosphorylation of the PFK2/FBPase-2 enzyme by cAPK requires cAMP. Levels of cAMP in the cell can be modulated hormonally. Glucagon and epinephrine increase cellular cAMP levels (favor gluconeogenesis), whereas insulin, decreases cellular cAMP levels, favoring removal of phosphates (stimulates glycolysis).