In glycolysis, what effect would high cellular ATP have on PFK-1 activity?

• A. Inhibit PFK-1 activity when ATP levels are high; glycolysis slows.
• B. Activate PFK-1 when ATP levels are high; glycolysis speeds up.
• C. No effect of ATP on PFK-1.
• D. Degrade PFK-1 when ATP high.

Answer: (A)

High cellular energy signals like ATP tell the cell that it doesn’t need to run glycolysis at full speed, so the activity of the main regulatory enzyme is reduced. Phosphofructokinase-1 (PFK-1) sits at a pivotal control point in glycolysis, converting fructose-6-phosphate to fructose-1,6-bisphosphate. When ATP is plentiful, it binds to an allosteric site on PFK-1 and inhibits the enzyme, lowering glycolytic flux. This prevents unnecessary glucose breakdown when energy is already sufficient. Conversely, when energy is scarce, AMP/ADP and fructose-2,6-bisphosphate activate PFK-1 to accelerate glycolysis and generate ATP. Regulation also integrates signals from the TCA cycle, with citrate providing additional inhibition when energy production is already high. So, high ATP slows glycolysis by inhibiting PFK-1.