Regulation of Phosphofructokinase Activity

The body’s metabolic pathways are tightly regulated to maintain homeostasis and respond to changing environmental conditions. One critical aspect of metabolism is the regulation of glycolysis, the primary pathway for glucose breakdown. Key enzymes in this pathway include hexokinase, phosphofructokinase (PFK), and pyruvate kinase. PFK is considered the most important regulatory enzyme in glycolysis due to its sensitivity to various allosteric effectors.

When examining PFK activity, it is known that ATP acts as an allosteric inhibitor, while fructose-2,6-bisphosphate (F-2,6-BP) serves as a potent allosteric activator. In the presence of high levels of AMP, PFK becomes stimulated, which encourages glycolysis to proceed, allowing for increased ATP production during times of low energy availability. Conversely, in a state of high ATP, PFK activity decreases, reflecting the cell's energy status.

Given this context, which of the following changes in cellular conditions is most likely to enhance the activity of phosphofructokinase?