Glycolysis regulation — Hexokinase catalyzes the first step of glycolysis. Which metabolite inhibits hexokinase activity by product feedback inhibition in most tissues?

Introduction:Entry of glucose into glycolysis is controlled at multiple levels. Hexokinase, the ubiquitous enzyme that phosphorylates glucose to glucose-6-phosphate (G6P), is regulated by feedback from its product to prevent excessive trapping of glucose in tissues when downstream pathways are saturated.

Given Data / Assumptions:

• Hexokinase converts glucose to G6P using ATP.
• G6P is a branch-point metabolite for glycolysis, glycogenesis, and the pentose phosphate pathway.
• Product inhibition is a common control mechanism for early pathway steps.

Concept / Approach:Determine which metabolite directly accumulates when downstream flux is limited and can bind hexokinase to reduce activity: glucose-6-phosphate. Other metabolites regulate different enzymes (e.g., ATP/citrate inhibit PFK-1, fructose-1,6-bisphosphate feed-forward activates pyruvate kinase), but they are not the hexokinase product.

Step-by-Step Solution:

Verification / Alternative check:Contrast with glucokinase (hepatic): it is not strongly inhibited by G6P and is regulated by sequestration (GKRP) and insulin, reflecting different physiological roles.

Why Other Options Are Wrong:

Common Pitfalls:Confusing hexokinase with hepatic glucokinase; mixing up regulators of PFK-1 with those of hexokinase.

Final Answer:Glucose-6-phosphate.