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Biochemistry · Molecular biology and genetics: cholera toxin and Gs
Sample itemIn severe cholera, the toxin of Vibrio cholerae causes massive intestinal secretion by raising cAMP in enterocytes. Which post-translational change in a signalling protein causes this?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
A. ADP-ribosylation of Gs alpha, which locks it in the GTP-bound active state
Cholera toxin ADP-ribosylates the alpha subunit of Gs, inhibiting its GTPase activity. Gs therefore stays active and keeps adenylate cyclase on, raising cAMP, activating CFTR and causing chloride and water secretion. Oral rehydration solution works because glucose-coupled sodium uptake is preserved.
Option by option
A. ADP-ribosylation of Gs alpha, which locks it in the GTP-bound active state (correct)
Correct. ADP-ribosylation blocks Gs GTPase, so adenylate cyclase stays active.
B. ADP-ribosylation of elongation factor 2, which halts protein synthesis
Elongation factor 2 is modified by diphtheria toxin, not cholera toxin.
C. Phosphorylation of Gs alpha by protein kinase A, which enhances GTP binding
Cholera toxin acts by ADP-ribosylation, not by PKA phosphorylation of Gs.
D. Proteolytic cleavage of adenylate cyclase, which activates it permanently
Adenylate cyclase is not cleaved; its activity rises through Gs.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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