Question

In one of the southern regions of the planet, several people were diagnosed with cholera. This is a particularly dangerous infectious disease that can spread rapidly if urgent measures are not taken. A patient with acute diarrhea, vomiting, muscle weakness, and spasms in the calf muscles was admitted to the admission department of the hospital. The skin of the hands is wrinkled, blood pressure is low. Examination of the patient confirmed the diagnosis of cholera. The causative agent of cholera, cholera vibrio, produces a toxin, one of the promoters of which is an enzyme - ADP-ribosyltransferase. Explain the mechanism of action of model toxin.
For an answer
1. Write the reactions catalyzed by this cholera toxin enzyme;
2. Explain the consequences of this reaction for the adenylate cyclase system in the cells of the intestinal mucosa;
3. Describe how cholera symptoms develop as a result of the toxin.

Answer 1

ADP ribosylation of membrane proteins are catalyzed by cholera toxin enzyme - ADP ribosyl transferase.

In the presence of ATP and a cytosolic factor, cholera toxin fragment A1 catalyzes the transfer of ADP ribose from NAD to a number of soluble and membrane bound proteins of the erythrocyte. The most readily modified membrane protein ( Mr 42000) is the adenylate cyclase associated GTP binding protein. It's modification by toxin is stimulated by guanine nucleotides. Adenylate cyclase activity increases in parallel with the addition of ADP ribose to this protein and decreases in parallel with the subsequent reversal of ADP ribosylation by toxin and nicotinamide.

The protein is only accessible to toxin A subunits if the erythrocytes are lysed. When adenylate cyclase activity reaches a maximum, the number of ADP ribose residues bound to this protein ( about 1500 per cell) is similar to the reported number of beta adrenergic receptors.

3. Cholera which is caused by Vibrio cholerae produces a toxin known as cholera toxin. This toxin causes the intestinal cells to release enormous amount of water leading to diarrhoea and loss of fluids and electrolytes ( electrolytes). Living in or traveling to areas where cholera is present raises the risk of getting it.