Question

Which observation suggested to Sutherland the involvement of a second messenger in epinephrine's effect on liver cells?

1) Glycogen breakdown was observed when epinephrine and glycogen phosphorylase were combined.
2) Glycogen breakdown was observed only when epinephrine was administered to intact cells.
3) Receptor studies indicated that epinephrine was a ligand.
4) Enzymatic activity was proportional to the amount of calcium added to a cell-free extract.
5) Epinephrine was known to have different effects on different types of cells.

Answer 1

Sutherland was led to the concept of a second messenger in epinephrine's effect on liver cells by the observation that glycogen breakdown requires the presence of intact cells, indicating a cascading signal involving cAMP.

Step-by-step explanation:

The observation that suggested to Sutherland the involvement of a second messenger in epinephrine's effect on liver cells was that glycogen breakdown was observed only when epinephrine was administered to intact cells. This is because, in a cell-free system where receptors and other cell components are not present, epinephrine alone cannot cause the breakdown of glycogen. However, in the presence of whole cells, epinephrine binding to the beta-adrenergic receptors triggers a cascade of events involving a second messenger, cyclic AMP (cAMP), which eventually leads to the activation of glycogen phosphorylase and the breakdown of glycogen.

cAMP is synthesized from ATP by the enzyme adenylyl cyclase, which is activated when epinephrine binds to the cell's beta-adrenergic receptor and activates a G-protein. The rise in cAMP levels in the cell acts as the secondary messenger in the signaling pathway, leading to various cellular responses including the conversion of glycogen to glucose.