Phosphofructokinase Is Inhibited By

Phosphofructokinase (PFK) is a key enzyme in the glycolysis pathway, responsible for catalyzing the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate. This enzymatic reaction is an essential step in cellular energy production. However, PFK is subject to inhibition by various factors that can regulate its activity. In this article, we will explore the different inhibitors of phosphofructokinase and their impact on cellular metabolism.

Phosphofructokinase is inhibited by several factors that can affect its activity and, consequently, the rate of glycolysis. Let’s dive into each of these inhibitors and understand their role in cellular metabolism.


One of the primary inhibitors of PFK is ATP, which is the end product of glycolysis. When ATP levels are high, it signals that the cell has sufficient energy supply and does not need to produce more. In this scenario, ATP binds to allosteric sites on PFK, inhibiting its activity and slowing down glycolysis. This negative feedback mechanism ensures that the cell does not waste energy by producing more ATP than it needs.


Citrate is an intermediate in the citric acid cycle, which is the primary pathway for ATP synthesis in the mitochondria. High levels of citrate indicate that energy production is sufficient, and there is no need for increased glycolysis. Citrate allosterically inhibits PFK, reducing the production of fructose-1,6-bisphosphate and slowing down the glycolytic flux.

pH and H+ ions

Changes in cellular pH can also affect the activity of PFK. Low pH levels (acidic conditions) result in an increased concentration of H+ ions. These ions can interact with PFK and inhibit its activity by disrupting its tertiary structure. The inhibition of PFK by H+ ions helps to maintain cellular pH homeostasis and prevent excessive acidification.


AMP, which is derived from ADP, can stimulate PFK activity. When the cell’s energy levels are low, the AMP/ATP ratio increases, signaling the need for more ATP production. AMP binds to specific allosteric sites on PFK, activating the enzyme and promoting glycolysis. This positive feedback mechanism ensures that the cell can respond to the increased demand for energy.

Feedback inhibition

Apart from the direct inhibitors mentioned above, PFK is also subject to feedback inhibition by some of the glycolytic intermediates. For example, high levels of ATP can stimulate the conversion of PEP (phosphoenolpyruvate) to pyruvate, bypassing the PFK-catalyzed step. This feedback loop helps regulate the flow of metabolites through the glycolytic pathway, ensuring energy balance and avoiding unnecessary ATP production.

Frequently Asked Questions

Q: Can PFK be permanently inhibited?

No, PFK is not permanently inhibited under normal physiological conditions. The inhibition of PFK is reversible, allowing the cell to adjust its metabolic flux based on energy demands. Once the inhibitory factors subside, PFK activity can be restored, and glycolysis can proceed.

Q: Are there any other regulators of PFK activity?

Yes, besides inhibition, PFK activity can also be regulated by other factors. Hormones like insulin and glucagon can modulate PFK activity to regulate glucose metabolism in response to different physiological states. Additionally, the concentration of NAD+ and ADP can affect PFK activity, providing further fine-tuning of glycolysis.

Q: What happens when PFK is inhibited?

When PFK is inhibited, the rate of glycolysis slows down. This can have various effects on cellular metabolism. For example, in muscle cells during intense exercise, PFK inhibition leads to a decrease in glycolytic flux, reducing the conversion of glucose to pyruvate for ATP production. The accumulation of glycolytic intermediates can also impact other metabolic pathways.

Final Thoughts

The inhibition of phosphofructokinase plays a crucial role in the regulation of cellular metabolism. By responding to intracellular energy demands and external factors, the inhibition of PFK controls the rate of glycolysis and helps maintain energy homeostasis. Understanding the different inhibitors of PFK and their impact on cellular metabolism provides valuable insights into the intricate regulation of energy production in our cells.

In summary, the inhibition of phosphofructokinase by ATP, citrate, pH/H+ ions, and feedback inhibition ensures that glycolysis is regulated according to the cell’s energy needs. These inhibitory mechanisms help maintain energy homeostasis and prevent the unnecessary production of ATP. By studying the intricacies of PFK regulation, researchers can gain a deeper understanding of cellular metabolism and potentially uncover new therapeutic targets for metabolic disorders.

Leave a Comment