Phosphofructokinase-2

One of the important allosteric effectors (molecules that bind to an allosteric site to affect kinetic properties) in liver cells is fructose-2,6-bisphosphate (F26BP). This not a metabolic compound, but exists primarily for the purpose of connecting glycolysis and gluconeogensis to hormonal regulation (more detail coming about this in the next couple of pages). The protein that synthesizes F26BP is unique in some ways. Recall that if there is an enzyme to put the phosphate on (using ATP of couse) then there must be another enzyme to hydrolyze the phosphate off of F26BP again. Indeed there is. It just so happens this time that BOTH of these enzyme activities reside on a single polypeptide.

This of course leads to some nomeclature problems.

F26BP formation nomeclature

	Reaction	Activity Name	Abbrev.
The active site that catalyzes the reaction	Fructose-6-P + ATP Fructose-2,6-Bisphophate + ADP	phosphofructokinase-2 (places PO4 on C2 of fructose)	PFK-2
The active site that catalyzes the reaction	Fructose-2,6-bisphosphate Fructose-6-P + PO4=	Fructose-2,6-bisphosphatase	F26BPase
What to call the entire peptide then???	theroretically catalyzes both reactions (we will modify this in a minute)	phosphofructokinase-2	PFK-2 / F26BPase or just one of these for convenience depending on activity

In general ONLY one of these activities is "active" at a time. This is a good thing since this single peptide could catalyze that "futile cycle" all by itself. The activities are modified by covalent modification vwith a phosphate group. More on how this gets there in the next two pages. Suffice it to say that It is placed on by an enzyme called "cyclic AMP dependent protein kinase" and removed by another enzyme (differnt polypeptide this time) called protein phosphatase. In the picture below, The yellow spheres represent the single polypeptide with the two activities PFK-2 and F26BPase; the * indicates the covalently modified peptide.
Recall, please that fructose-2,6-bisphophate is an activator of glycolysis (by way of stabilizing the GOOD form of the metabolic enzyme phosphofructokinase-1 ) and an inhibitor of gluconeogenesis (by way of stabilizing the POOR form of fructose-1,6-bisphosphatase).