Question

Identify the correct order of events when epinephrine binds to \(\beta\)-receptor of the biological membrane.
A. Binding of GTP and release of GDP from \(\alpha\)-subunit of G-Protein.
B. Interaction of hormone bound \(\beta\)-receptor with \(\beta\gamma\) - subunit of G-Protein.
C. Binding of GTP bound \(\alpha\)-subunit of G-protein with Adenyl cyclase
D. Activation of dephosphorylation
E. Activation of phosphorylation
F. Activation of formation of cAMP
Choose the correct answer from the options given below:

• A. B, A, C, D, E, F
• B. B, A, C, F, E, D
• C. C, B, F, E, A, D
• D. B, C, A, D, F, E

Hint:

GPCR activation always follows the sequence: ligand binding \(\rightarrow\) receptor conformational change \(\rightarrow\) GDP-GTP exchange on G\(\alpha\) \(\rightarrow\) effector enzyme activation \(\rightarrow\) second messenger production.

Answer 1

The Correct Option is B

Step 1: Understanding the Concept:
Epinephrine binds to \(\beta\)-adrenergic receptors on the cell membrane, which are seven-transmembrane G-protein-coupled receptors (GPCRs).
This binding initiates an intracellular signal transduction cascade mediated by heterotrimeric G-proteins.

Step 2: Detailed Explanation:
Let us trace the sequential steps of this pathway:
Event B: Epinephrine binds to the \(\beta\)-adrenergic receptor, inducing a conformational change that allows the activated receptor to interact with the \(\beta\gamma\)-subunit of the adjacent heterotrimeric \(G_s\) protein complex.
Event A: This interaction promotes a conformational change in the G-protein's \(\alpha\)-subunit, triggering the release of bound GDP and the binding of GTP.
Event C: The GTP-bound \(\alpha\)-subunit (\(G_{\alpha s}\)) dissociates from the \(\beta\gamma\)-dimer and binds to the membrane-bound enzyme adenylyl cyclase, activating it.
Event F: Activated adenylyl cyclase catalyzes the conversion of ATP into the second messenger cyclic AMP (cAMP).
Event E: Rising cAMP levels activate Protein Kinase A (PKA), which phosphorylates target intracellular proteins (activation of phosphorylation).
Event D: To terminate the signal, phosphodiesterases degrade cAMP, and protein phosphatases remove the phosphate groups from target proteins (activation of dephosphorylation).
This sequence of events corresponds to the order: B \(\rightarrow\) A \(\rightarrow\) C \(\rightarrow\) F \(\rightarrow\) E \(\rightarrow\) D.

Step 3: Final Answer:
The correct order of events is B, A, C, F, E, D.