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Phosphofructokinase (PFK-1) regulation

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.

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Phosphofructokinase (PFK-1) regulation

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

  2. 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.

  3. 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

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

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

  6. 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

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

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