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

• http://cmgm.stanford.edu/biochem200/regulation/

• Lehninger Principles of Biochemistry by Nelson and Cox