Question

How does the presence of the poorly hydrolyzable GTP analog GTP$\mathit{\gamma }$S (in which an O atom on the terminal phosphate is replaced by an S atom) affect cAMP production by adenylate cyclase?

Short answer

$\text{GTP}\gamma \text{S}$bound to${\text{R}}_{\text{S}}$ will promote cAMP production, but bound to ${\text{R}}_I$inhibits it.

Step-by-step solution

Outcomes of poorly hydrolysableof GTP

$\mathbf{\text{GTP}}\mathit{\gamma }\mathbf{\text{S}}$cannot be hydrolyzed, which has two possible outcomes:

Binding of$\mathbf{\text{GTP}}\mathit{\gamma }\mathbf{\text{S}}$ to ${\mathbf{\text{R}}}_{\mathbf{\text{S}}}$causes uninhibited production of cAMP, since hydrolysis of bound $\mathbf{\text{GTP}}\mathit{\gamma }\mathbf{\text{S}}$to GDP stops the production.

Explanation

Binding of$\text{GTP}\gamma \text{S}$ to ${\text{R}}_I$causes no cAMP to be produced because${\text{G}}_{\text{Iα}}$. GTP complex inhibits adenylate cyclase, and $\text{GTP}\gamma \text{S}$can't be hydrolysed to restore the activity.