​In a mammalian cell undergoing active glycolysis, what would be the effect of a sudden increase in the concentration of metabolites, AMP, citrate, ATP, and glucose-6-phosphate?

(A) Increased ATP inhibits glycolysis.
(B) Increased AMP stimulates glycolysis.
(C) Increased citrate and glucose-6-phosphate stimulate glycolysis.
(D) Increased AMP and citrate inhibit glycolysis.

Which one of the following represents the combination of all correct statements?

Correct option is C

​Glycolysis is regulated by several key metabolites that act as activators or inhibitors of rate-limiting enzymes such as phosphofructokinase-1 (PFK-1) and pyruvate kinase.

1. ATP and Glycolysis (A is Correct )
• ATP is an allosteric inhibitor of glycolysis, particularly of phosphofructokinase-1 (PFK-1).
• When ATP levels are high, cells do not need more energy, so glycolysis is slowed down.
2. AMP and Glycolysis (B is Correct )
• AMP is a key activator of glycolysis.
• High AMP levels indicate low energy (ATP is depleted), leading to activation of PFK-1 and stimulation of glycolysis.
3. Citrate and Glucose-6-Phosphate (C is Incorrect )
• Citrate inhibits glycolysis (not stimulates it), acting as a feedback inhibitor of PFK-1.
• Glucose-6-phosphate regulates glycolysis indirectly, but it mainly regulates glycogen synthesis.
4. AMP and Citrate (D is Incorrect )
• AMP stimulates glycolysis, not inhibits it.
• Citrate inhibits glycolysis, but this statement is incorrect because AMP and citrate do not both inhibit glycolysis.

Thus, the correct answer is (c) A and B.

Information Booster:

• Phosphofructokinase-1 (PFK-1) is the rate-limiting enzyme of glycolysis.
• High ATP inhibits PFK-1, slowing glycolysis to prevent excess ATP production.
• AMP is a strong activator of PFK-1, ensuring glycolysis continues when ATP is low.
• Citrate is an indicator of the TCA cycle's activity and inhibits glycolysis when the cell has sufficient energy.
• Glucose-6-phosphate inhibits hexokinase, preventing unnecessary glucose breakdown when sufficient glucose is available.

Additional Knowledge:

(A) ATP Inhibits Glycolysis (Correct)

• ATP binds to PFK-1, reducing its activity.
• When ATP is high, glycolysis is downregulated to prevent excessive ATP production.
• Example: Resting muscle has high ATP, leading to glycolysis inhibition.

(B) AMP Stimulates Glycolysis ( Correct)

• AMP activates PFK-1, promoting glycolysis.
• High AMP signals low cellular energy.
• Example: Intense exercise increases AMP, activating glycolysis.

(C) Citrate and Glucose-6-Phosphate Stimulate Glycolysis ( Incorrect)

• Citrate inhibits glycolysis by allosterically inhibiting PFK-1.
• Glucose-6-phosphate primarily regulates glycogen metabolism rather than glycolysis.

(D) AMP and Citrate Inhibit Glycolysis (Incorrect)

• AMP stimulates glycolysis, while citrate inhibits it.
• This statement is incorrect as both do not inhibit glycolysis.