Phosphofructokinase (PFK-1) regulation Cristian Ascencio and Evan Parker

PFK-1 commits hexoses to glycolysis The glycolysis product glucose- 6-phosphate can be used for both glycolysis and glycogen formation. Phosphorylation of Fructose-6 phosphate is an irreversible step that expends cellular ATP and commits hexoses to glycolysis. The enzyme PFK-1 must be regulated to ensure optimal resource usage.

PFK-1 regulation PFK-1 is ATP dependent and its activity is increased by ATP availability. At higher levels of ATP, the ATP binds to allosteric regulation sites reducing the activity. ADB also binds to allosteric regulation sites activating PFK-1. – The balance between ATP and ADP in the cell is indicative of energy usage and is the regulator system for PFK-1

ATP in allosteric inhibition site (PDB ID = 3O8L)

ADP in allosteric activation site (PDB ID = 1PFK)

Bound ATP rotates the positions of Arg162 and Glu161 the positive charge on Arg162 stabilizes the negative charge on the phosphate of F6P, and Km is low The negative charge on Glu161 repulses the F6P and raises the Km

References PDB.org; 1PFK, 3O8L Lehninger Principles of Biochemistry by Nelson and Cox