Chemical Explanation (Annals of the New York Academy of by International Society for the Philosophy of Chemistry;

By International Society for the Philosophy of Chemistry; Joseph E. Earley, Sr.

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38 CUATRECASAS I'll make this very simple, just to convey the basic aspects of their chemistry, but of course it is much more complicated. The basic structural unit of sphingolipids is the ceramide portion, which consists of a fatty aciGl attached to sphingosine. The latter is really a generic name. There are many kinds of sphingosines. The C-18 derivative is a prototype. Basically all we need is a long chain base having a 2 -amino1, 3-diol derivative. However, in some cases there are no double bonds, or two double bonds, and there may be other hydroxyl groups.

Is it truly a receptor, or is it something else? The answer is that it does modify the response. Under certain conditions, if one manipulates the system correctly, it is possible to observe no biological response in untreated cells, while there is a maximal response in cells which have been treated with GM 1. The difference in activity is accounted for by an increase in the amount of binding in the cells treated with GM 1. It is very probable that GM I ganglioside is the chemical receptor for cholera toxin.

We favor the latter since there is evidence for multivalency, and we feel that there must be at least two binding sites for gangliosides in the native molecule. In SDS it is possible to dissociate the active and the binding subunits. Interestingly, the binding unit, the choleragenoid, does not dissociate in SDS unless it is heated. This is thus another example of a non -membrane protein which is not readily dissociated by SDS. The active unit alone does not bind, and is devoid of biologic activity.

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