Sections 15.1, 15.5  



Phosphofructokinase (PFK) is a glycolytic enzyme that catalyzes the irreversible transfer of a phosphate from ATP to fructose-6-phosphate:

fructose-6-phosphate + ATP fructose-1,6-bisphosphate + ADP

In part because of the irreversible nature of this step in glycolysis, PFK is the key regulatory enzyme for glycolysis. When ATP levels are high in the cell, the cell no longer needs metabolic energy production to occur. In this case, PFK's activity is inhibited by allosteric regulation by ATP itself, closing the valve on the flow of carbohydrates through glycolysis. Recall that allosteric regulators bind to a different site on the enzyme than the active (catalytic) site. Thus ATP binds in two places on PFK: in the active site as a substrate and in the regulatory site as a negative modulator. ATP bound in the regulatory site acts as a modulator by lowering the affinity of PFK for its other substrate, fructose-6-phosphate.

Modulators of PFK


Inhibitor (-)
Inhibitor (-)
Activator (+)

PFK is also inhibited by abundant cellular concentrations of citrate, another marker of a high energy state of a cell. When citrate levels are high, the cell can obtain more than enough energy from the citric acid cycle and does not need glycolysis to shovel more carbons into the citric acid cycle.

Perhaps the most interesting modulator of PFK is fructose-2,6-bisphosphate. It acts to stimulate PFK in liver cells, although its mode of action is not currently well understood.

Relevant Units

Glycolysis animation
Citric Acid Cycle animation

Copyright 2002, John Wiley & Sons Publishers, Inc.