Covalent modification of enzymes by phosphorylation is a key regulatory mechanism. Phosphorylation of glycogen synthase INACTIVATES it while phosphorylation of glycogen phosphorylase ACTIVATES it. What is the net effect when glucagon elevates cAMP?

• A Glycogen synthesis is stimulated; glycogenolysis is inhibited
• B Both glycogen synthesis and glycogenolysis are simultaneously stimulated
• C Glycogenolysis is stimulated and glycogen synthesis is simultaneously inhibited, maximizing glucose output ✓
• D Glycogen synthase is activated while phosphorylase is inhibited, promoting glycogen synthesis

Explanation

Glucagon → Gs-coupled receptor → cAMP → PKA activation. PKA phosphorylates: (1) phosphorylase kinase (activates it), which phosphorylates glycogen phosphorylase b → active 'a' form (glycogenolysis ON); (2) glycogen synthase → inactive phosphorylated form (glycogen synthesis OFF). This reciprocal regulation ensures maximum hepatic glucose output during fasting/hypoglycemia. PKA also phosphorylates phosphodiesterase (delayed negative feedback), PP1 inhibitor-1 (inhibiting the phosphatase that would reverse these effects), and transcription factors for gluconeogenic gene expression.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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