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Biochemistry

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Vitamins, Harmones and Hemoglobin

Question
13 out of 30
 

By which of the following actions GS receptor can be stimulated to induce watery diaorrhea (AIIMS May 2011)



A Phosphorylation
B Dephosphorylation

C ATP-ADP exchange
D ADP ribosylation

Ans. D The answer can be Cyclic AMP if it is option or ribosylation of G regulator protein. Please check for any typographic errors.

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.

Reference :

Harper’s Biochemistry, 24th Edition, Pg. 514-515

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