ATP regulates glycolysis primarily by inhibiting the enzyme phosphofructokinase (PFK), a key regulatory point in the pathway.
Role of Phosphofructokinase (PFK)
Phosphofructokinase is the main enzyme controlled in glycolysis. Its activity is influenced by several factors, including ATP levels.
ATP as an Allosteric Inhibitor
High levels of ATP signal that the cell has sufficient energy. To prevent overproduction of ATP, it inhibits glycolysis through PFK. Specifically, ATP binds to an allosteric site on the enzyme to inhibit its activity. This binding changes the enzyme's conformation, reducing its affinity for its substrate, fructose-6-phosphate.
| Regulator | Effect on PFK Activity |
|---|---|
| ATP | Inhibits |
| Citrate | Inhibits |
| Acidic pH | Inhibits |
| AMP | Activates |
Mechanism of Inhibition
Here's a breakdown of how ATP regulates PFK:
- Allosteric Binding: ATP binds to a regulatory site (allosteric site) on PFK, distinct from the active site where fructose-6-phosphate binds.
- Conformational Change: This binding induces a conformational change in the enzyme.
- Decreased Affinity: The conformational change reduces the enzyme's affinity for its substrate, fructose-6-phosphate.
- Reduced Activity: As a result, the rate of glycolysis decreases.
Other Regulatory Factors
While ATP is a crucial regulator, other molecules also influence PFK activity:
- Citrate: A product of the citric acid cycle, also inhibits PFK, indicating sufficient energy production.
- AMP: When ATP levels are low, AMP (adenosine monophosphate) accumulates and acts as an activator of PFK, stimulating glycolysis to produce more ATP.
- pH: A more acidic pH inhibits PFK, preventing excessive lactic acid buildup during anaerobic conditions.
