Multiple Choice
If a chemical is an inhibitor of the enzyme adenylyl cyclase, which of the following steps in the GPCR signaling pathway would be directly blocked?
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12. Biosignaling
Inhibitory Adenylate Cyclase GPCR Signaling
Multiple Choice
The addition of the nonhydrolyzable GTP-analog, GTPγS (shown below), is a common cell culture technique. If only affecting the inhibitory pathway, what effect would GTPγS have on cellular cAMP levels?
A
cAMP levels increase because adenylate cyclase can no longer hydrolyze GTP.
B
cAMP levels decrease because Gs remains in its inactive state and can no longer bind GDP.
C
cAMP levels decrease because Gi remains in its active state since it can no longer hydrolyze GTP.
D
cAMP levels increase because Gi remains in its inactive state since it can no longer hydrolyze GTP.
Verified step by step guidance1
Understand the role of GTP in cellular signaling: GTP is a molecule that binds to G-proteins, which are involved in transmitting signals from outside the cell to the inside. When GTP is bound, the G-protein is active; when GDP is bound, it is inactive.
Identify the effect of GTPγS: GTPγS is a nonhydrolyzable analog of GTP, meaning it can bind to G-proteins but cannot be hydrolyzed to GDP. This means that G-proteins remain in their active state when bound to GTPγS.
Focus on the inhibitory pathway: In the context of the problem, we are interested in the inhibitory G-protein (Gi). Normally, Gi inhibits adenylate cyclase, reducing cAMP levels when active.
Analyze the effect of GTPγS on Gi: Since GTPγS cannot be hydrolyzed, Gi remains in its active state, continuously inhibiting adenylate cyclase. This leads to a decrease in cAMP levels because adenylate cyclase activity is reduced.
Conclude the effect on cAMP levels: With Gi remaining active due to the presence of GTPγS, cAMP levels decrease as adenylate cyclase is inhibited and cannot produce cAMP efficiently.
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