Metabolic regulation — Which of the following is NOT a common mechanism to alter flux through a pathway’s rate-determining step?

Introduction / Context:
Cells regulate metabolic flux at key control points to match supply with demand. Understanding bona fide mechanisms helps distinguish real regulatory strategies from implausible or rarely relevant concepts.

Given Data / Assumptions:

• Rate-determining steps are often catalyzed by enzymes subject to regulation.
• Mechanisms include rapid (allosteric, covalent) and slow (transcriptional) control.
• We must identify the option that is not a recognized regulatory mechanism.

Concept / Approach:
Allosteric control modulates activity via effector binding. Covalent modifications such as phosphorylation switch activity states. Genetic control adjusts enzyme abundance by altering transcription/translation. “Diffusional coupling between adjacent active sites” is not a standard regulatory mechanism for pathway flux; while substrate channeling can occur in multienzyme complexes, “diffusional coupling” is not used as a primary control strategy to set pathway rate in textbooks.

Step-by-Step Solution:

Verification / Alternative check:
Classic examples: PFK-1 (allosteric), glycogen phosphorylase (phosphorylation), and lipid metabolism (transcriptional regulation by SREBP/PPAR) illustrate the three accepted mechanisms.

Why Other Options Are Wrong:

• Allosteric control is widespread (ATP, AMP, citrate, F2,6BP).
• Genetic control changes Vmax by altering enzyme concentration.
• Covalent modification provides rapid, reversible switches.

Common Pitfalls:
Confusing physical proximity or metabolon formation with deliberate regulatory control; although it may influence kinetics, it is not a canonical flux control mechanism taught at this level.

Final Answer:
Diffusional coupling between adjacent active sites