Fructose-2,6-bisphosphate (F-2,6-BP) is the most potent allosteric activator of PFK-1. Glucagon decreases hepatic F-2,6-BP by:

• A Inhibiting glucokinase activity directly
• B Directly inhibiting PFK-1 by binding its allosteric site
• C Activating PKA, which phosphorylates PFK-2/FBPase-2 bifunctional enzyme, activating its FBPase-2 activity and inactivating its PFK-2 kinase activity ✓
• D Upregulating PEPCK to divert F-6-P toward gluconeogenesis

Explanation

Glucagon → cAMP → PKA phosphorylates the bifunctional PFK-2/FBPase-2 enzyme at Ser32; phosphorylation activates the FBPase-2 domain (which degrades F-2,6-BP) and inactivates the PFK-2 kinase domain (which synthesises F-2,6-BP), decreasing F-2,6-BP and thereby reducing PFK-1 activity to slow glycolysis. Insulin does the opposite. This is the key hormonal switch for glycolysis/gluconeogenesis in the liver.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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