Glucagon activates glycogen phosphorylase in hepatocytes through a second messenger cascade. The rate-limiting amplification step in this cascade, making even nanomolar glucagon concentrations effective, is:

• A Each glucagon molecule directly activates thousands of glycogen phosphorylase molecules
• B cAMP directly dephosphorylates glycogen phosphorylase b converting it to the active a form
• C Each activated PKA molecule can phosphorylate multiple phosphorylase kinase molecules, each of which phosphorylates multiple phosphorylase molecules ✓
• D Glucagon receptor internalisation concentrates signal to the mitochondrial membrane

Explanation

The glucagon cascade achieves massive signal amplification through sequential enzymatic cascades. One glucagon molecule activates Gsα → adenylyl cyclase → many cAMP molecules → multiple PKA holoenzymes. Each active PKA catalytic subunit phosphorylates multiple phosphorylase kinase molecules; each activated phosphorylase kinase then phosphorylates multiple glycogen phosphorylase b molecules, converting them to the active phosphorylase a form. This cascading enzymatic amplification means a single hormone molecule ultimately mobilises millions of glucose units. cAMP does not directly modify phosphorylase, and receptor internalisation terminates rather than amplifies signalling.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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