Cholera toxin causes persistent diarrhoea by covalently modifying the alpha subunit of Gs protein. What is the biochemical mechanism?
- A Phosphorylation of Gsα, leading to its dissociation from the receptor
- B ADP-ribosylation of Giα, preventing inhibition of adenylyl cyclase
- C ADP-ribosylation of Gsα preventing GTP hydrolysis, locking adenylyl cyclase in a constitutively active state ✓
- D Ubiquitination of Gsα, leading to its proteasomal degradation
Correct answer: C. ADP-ribosylation of Gsα preventing GTP hydrolysis, locking adenylyl cyclase in a constitutively active state
Explanation
Cholera toxin catalyzes ADP-ribosylation of an arginine residue on the alpha subunit of the stimulatory G-protein (Gsα), inhibiting its intrinsic GTPase activity. Without GTP hydrolysis, Gsα remains permanently activated, constitutively stimulating adenylyl cyclase and producing excess cAMP in intestinal epithelial cells. Elevated cAMP activates PKA → phosphorylation of CFTR chloride channels → massive Cl⁻ (and water) efflux causing secretory diarrhoea. Pertussis toxin similarly ADP-ribosylates Giα.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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