Glycolysis Regulation

Regulation of Glycolysis

• Glycolysis is regulated at 3 steps that are the most exergonic and irreversible.
• These 3 reactions are catalyzed by enzymes that are allosterically regulated.
• This means they are regulated by a molecule binding to another site that is not its active site.

1. Hexokinase
2. Phosphofructokinase
3. Pyruvate Kinase

Hexokinase

• Inhibited by the product it makes: G6P.
• Enzyme active when G6P levels are low (when glycolysis is active).
• Enzyme inhibited when G6P levels are high (when glycolysis slows down).

• The key regulator of carbohydrate metabolism in the cell.
• PFK inhibitors:
• High levels of ATP
• When too much ATP is present, it can bind to the regulatory site on the enzyme and lower its affinity for the substrate.
• High levels of citrate
• As citrate builds up form TCA cycle, it causes glycolysis to slow down by inhibiting PFK.
• Protons (H+)
• Prevents excessive formation of lactic acid.
• Low pH (acidic conditions) will inhibit PFK.
• PFK activators:
• High levels of AMP
• AMP competes with ATP for binding the PFK regulatory site.
• AMP binding at the regulatory site prevents ATP binding → no inhibition of PFK by ATP.
• Think about it like this: if there's a lot of AMP, there's low ATP. Therefore, we need more glycolysis.
• High levels of Fructose-2,6-Bisphosphate (F-2,6-BP)
• Enhances PFK activity by increasing the affinity of PFK to its substrate F6P.

Pyruvate Kinase

• Main function is to produce pyruvate + ATP.
• Pyruvate kinase inhibitors:
• High levels of ATP
• The amino acid alanine
• Pyruvate kinase activators:
• High levels of Fructose-1,6-Bisphosphate (F-1,6-BP)