Cholera toxin causes persistent diarrhoea by ADP-ribosylating which protein, and what is the functional consequence?

• A Giα, preventing GTP hydrolysis and constitutively activating adenylyl cyclase
• B Adenylyl cyclase directly, increasing cAMP synthesis
• C Gsα, preventing GTP hydrolysis and constitutively activating adenylyl cyclase ✓
• D Protein kinase A regulatory subunit, causing constitutive PKA activation

Explanation

Cholera toxin ADP-ribosylates the arginine residue (Arg201) of Gsα, preventing its intrinsic GTPase activity. This locks Gsα in the GTP-bound active conformation, constitutively stimulating adenylyl cyclase and massively elevating intracellular cAMP. In intestinal epithelial cells, elevated cAMP activates PKA, which phosphorylates CFTR channels and inhibits NaCl absorption via Na+/H+ exchanger inhibition, causing secretory diarrhoea. Pertussis toxin ADP-ribosylates Giα (not Gsα) to prevent Giα coupling. Cholera toxin does not directly modify adenylyl cyclase or PKA.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.