Integrated regulation — Which signaling metabolite most directly coordinates opposing fluxes of glycolysis and gluconeogenesis in liver in response to insulin/glucagon?

Introduction:
Hepatic carbohydrate metabolism must balance glycolysis (glucose utilization) against gluconeogenesis (glucose production). A single allosteric regulator, fructose-2,6-bisphosphate (F-2,6-BP), provides powerful reciprocal control of the two opposing pathways in response to hormonal cues.

Given Data / Assumptions:

• F-2,6-BP is synthesized and degraded by the bifunctional enzyme PFK-2/FBPase-2.
• Insulin increases F-2,6-BP (via dephosphorylation), stimulating glycolysis.
• Glucagon decreases F-2,6-BP (via phosphorylation), favoring gluconeogenesis.

Concept / Approach:
Identify the metabolite that directly and reciprocally regulates PFK-1 and fructose-1,6-bisphosphatase (FBPase-1). F-2,6-BP is the key: it activates PFK-1 (promoting glycolysis) and inhibits FBPase-1 (suppressing gluconeogenesis), thereby coordinating hepatic glucose flux with the hormonal state that also influences glycogen metabolism.

Step-by-Step Solution:

Verification / Alternative check:
Hepatocyte studies show that altering F-2,6-BP levels rapidly shifts glycolytic/gluconeogenic flux independent of changes in total metabolite pools.

Why Other Options Are Wrong:

Common Pitfalls:
Confusing fructose-2,6-bisphosphate (regulator) with fructose-1,6-bisphosphate (intermediate); conflating hormonal kinases with small-molecule allosteric effectors.

Final Answer:
Fructose-2,6-bisphosphate.