The nature and action of cholera toxin.
Cholera diarrhoea is due to the action of a toxin that acts on all animal cells by stimulating the enzyme adenylate cyclase, which catalyses the production oc cyclic AMP from ATP. In intestinal brush border cells raised cyclic AMP levels result in increased secretion of chloride ions, leading to fluid accumulation in the gut. Escherichia coli produces a similar toxin. The receptor for cholera toxin on the cell membrane appears to be a complex containing the ganglioside GGnSLC (or GM1). Cholera toxin is a protein composed of two different kinds of subunits linked non-covalently. Each toxin molecule has one subunit A and four or more subunits B. Subunit B is inactive but binds to the ganglioside GGnSLC on the cell surface. Subunit A does not bind to cell membranes or gangioside and is slightly toxic to intact cells but strongly and instantly active in lysed cells. The binding of whole toxin through the B subunit to the cell is followed by a lag before subunit A penetrates the cell membrane (leaving subunit B on the surface) and stimulates the adenylate cyclase. The stimulation of adenylate cyclase depends on the presence of NAD and other co-factors present in the cell sap.
D000262:Adenylyl Cyclases / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004768:Enterotoxins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008970:Molecular Weight; D011506:Proteins / Q000302:isolation & purification; D013268:Stimulation, Chemical; D014734:Vibrio cholerae
D002712:Chlorides; D004768:Enterotoxins; D011506:Proteins; D000262:Adenylyl Cyclases