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NBME 18 Answers

nbme18/Block 1/Question#28 (6.3 difficulty score)
Cholera toxin is a catalyst that results in ...
Concentration of cAMP🔍
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Cholera roxin overactivates adenylate cyclase ( increases cAMP) by permanently activating Gs and thus icnreases Cl- secretion in the gut and H20 efflux Page 132 FA 2018




G-protein coupled receptors bind to GTP in the activated state and to GDP in the inactivated state. So inhibition of the GTPase keeps the receptor from turning GTP to GDP and thus it remains constitutively active (this is what tripped me up). Now that we know the Gs protein is overactive, then we know everything downstream is overproduced. Gs activates adenylyl cyclase which turns ATP to cAMP and thus cAMP is increased. No need to even know anything about Cholera if you understand the biochem.

Otherwise, you can remember that Cholera toxin over activates adenylyl cyclase and thus releases Cl- resulting in H2O loss.

I think about it as kind of like the opposite of cystic fibrosis, so in this case, the increased secretion of Cl- leads to less Na+ absorption and thus less H2O absorption (H2O efflux).