Question

Which of the following enzymes is active in its dephosphorylated state?

• A. Glycogen synthase
• B. Glycogen phosphorylase
• C. PFK-2 (phosphofructokinase-2)
• D. Fructose-2,6-bisphosphatase

Hint:

Fed-state insulin dephosphorylates and switches ON the glycogen-storing enzyme.

Answer 1

The Correct Option is A

Step 1: Understand the covalent regulation.
Many metabolic enzymes are regulated by reversible phosphorylation. Phosphorylation (driven by cAMP-dependent protein kinase A in the fasting/adrenaline state) and dephosphorylation (driven by protein phosphatase-1 in the fed/insulin state) switch enzymes ON or OFF depending on whether the body needs to store or mobilise fuel.

Step 2: Apply it to glycogen metabolism.
In the well-fed state, insulin promotes dephosphorylation. Glycogen synthase is active (a) in its dephosphorylated form, favouring glycogen synthesis. Conversely, glycogen phosphorylase is active (a) in its phosphorylated form, favouring glycogen breakdown. The two are reciprocally regulated so synthesis and degradation do not occur simultaneously.

Step 3: Eliminate the other options.
Glycogen phosphorylase to active when phosphorylated. The bifunctional PFK-2/fructose-2,6-bisphosphatase enzyme: when dephosphorylated the kinase (PFK-2) domain is active (raising fructose-2,6-bisphosphate, promoting glycolysis), and when phosphorylated the phosphatase (F-2,6-BPase) domain is active. So PFK-2 active dephosphorylated is also true in the liver, but the single classical ‘dephosphorylated = active’ storage enzyme tested here is glycogen synthase.

Key fact: Glycogen synthase is the storage-promoting enzyme that is switched ON by dephosphorylation in the insulin-driven fed state.