Vitamins, Harmones and Hemoglobin
By which of the following actions GS receptor can be stimulated to induce watery diaorrhea (AIIMS May 2011)
a. The cholera toxin (CTX or CT) is an oligomeric complex made up of six protein subunits: a single copy of the A subunit (part A), and five copies of the B subunit (part B), connected by a disulfide bond.
b. The five B subunits form a five-membered ring that binds to GM1 gangliosides on the surface of the intestinal epithelium cells.
c. The A1 portion of the A subunit is an enzyme that ADP-ribosylates G proteins, while the A2 chain fits into the central pore of the B subunit ring. Upon binding, the complex is taken into the cell via receptor-mediated endocytosis.
d. Once inside the cell, the disulfide bond is reduced, and the A1 subunit is freed to bind with a human partner protein called ADP-ribosylation factor 6 (Arf6).
e. Binding exposes its active site, allowing it to permanently ribosylate the Gs alpha subunit of the heterotrimeric G protein. This results in constitutive cAMP production, which in turn leads to secretion of H2O, Na+.
f. K+, Cl−, and HCO3− into the lumen of the small intestine and rapid dehydration. Thus in the small intestine, cholera toxin acts by ADP – ribosylation of the G regulatory protein.
Harper’s Biochemistry, 24th Edition, Pg. 514-515