Question

Whenever the cell's ATP supply is depleted, which of the following enzyme’s activity is increased?

• A. Hexokinase
• B. Pyruvate kinase
• C. Glucokinase
• D. Phosphofructokinase-1

Hint:

PFK-1 is a key regulatory enzyme in glycolysis, and its activity is enhanced during low ATP conditions to promote energy production.

Answer 1

The Correct Option is D

Step 1: Understanding ATP depletion in cells.
When ATP levels are low, cells activate pathways to restore ATP, often by increasing the rate of glycolysis. Phosphofructokinase-1 (PFK-1) is a key regulatory enzyme in glycolysis, and its activity is typically increased when ATP levels are low.
Step 2: Analyzing the options.
(1) Hexokinase: Hexokinase is involved in the initial steps of glycolysis but is not as closely regulated by ATP levels.
(2) Pyruvate kinase: Pyruvate kinase is important in the final step of glycolysis but is not the most direct regulator when ATP levels are low.
(3) Glucokinase: Glucokinase is a type of hexokinase found in the liver, and while it is involved in glucose metabolism, it is not the most important enzyme for regulating ATP levels.
(4) Phosphofructokinase-1: Correct — PFK-1 is the rate-limiting enzyme in glycolysis, and its activity is upregulated when ATP levels are depleted to increase the production of ATP.
Step 3: Conclusion.
The correct answer is (4) Phosphofructokinase-1, as its activity increases when the cell's ATP supply is low.

Answer 2

When ATP is depleted, cells need to accelerate glycolysis to regenerate it, and the enzyme most sensitive to this signal is the one allosterically regulated by the ATP/AMP ratio. Checking each option:

1. Hexokinase: Hexokinase is inhibited by its own product, glucose-6-phosphate, and is not the primary enzyme whose activity is directly boosted by falling ATP levels.
2. Pyruvate kinase: Pyruvate kinase catalyses the final step of glycolysis and is regulated mainly by fructose-1,6-bisphosphate and hormonal phosphorylation, rather than being the primary direct sensor of ATP depletion.
3. Glucokinase: Glucokinase, the liver-specific hexokinase isoform, is regulated mainly by glucose concentration and is not allosterically switched on by low ATP.
4. Phosphofructokinase-1: PFK-1 is directly inhibited by ATP and citrate when energy is abundant, and directly activated by AMP and ADP when ATP is depleted, making it the rate-limiting checkpoint of glycolysis that speeds up specifically in response to falling cellular energy charge.

Because PFK-1's allosteric regulation is built specifically around sensing the ATP-to-AMP balance, it is the enzyme whose activity rises when ATP supply is depleted.

Therefore, the correct answer is phosphofructokinase-1.