Phosphofructokinase (PFK-1) regulation

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Phosphofructokinase (PFK-1) regulation

• Cristian Ascencio and Evan Parker

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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.
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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

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ATP in allosteric inhibition site (PDB ID 3O8L)
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ADP in allosteric activation site (PDB ID 1PFK)
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• 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

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References

• PDB.org 1PFK, 3O8L
• http//cmgm.stanford.edu/biochem200/regulation/
• Lehninger Principles of Biochemistry by Nelson
  and Cox