Citrate accumulation and glycolysis/gluconeogenesis control If mitochondrial citrate accumulates and is exported to the cytosol, what regulatory effects does this have on key opposing enzymes?

Introduction / Context:
Cellular energy status is integrated through allosteric regulators. Citrate links the citric acid cycle to glycolysis and gluconeogenesis. High citrate indicates ample biosynthetic precursors and energy, signaling the cell to slow glycolysis while favoring glucose production/storage pathways.

Given Data / Assumptions:

• Citrate exits mitochondria when abundant and acts in the cytosol.
• PFK-1 is a rate-limiting enzyme of glycolysis.
• FBPase-1 is a rate-limiting enzyme of gluconeogenesis.

Concept / Approach:

Citrate is an allosteric inhibitor of PFK-1, decreasing glycolytic flux. Conversely, citrate can promote gluconeogenic direction by favoring FBPase-1 activity (often indirectly coordinated with low fructose-2,6-bisphosphate). Together, these actions prevent futile cycling and balance energy homeostasis.

Step-by-Step Solution:

Verification / Alternative check:

Classic enzyme kinetics experiments show citrate shifts PFK-1 to a less active state and supports gluconeogenic control when coupled with hormonal regulation (glucagon).

Why Other Options Are Wrong:

Option A contradicts known inhibition. Option B alone is incomplete. Option C alone is partial. Option E ignores well-established allosteric control.

Common Pitfalls:

Forgetting that citrate also indicates abundant acetyl-CoA and can support fatty acid synthesis while braking glycolysis.

Final Answer:

Both stimulation of FBPase-1 and inhibition of PFK-1