DAVID NACHMANSOHN AND IRWIN B. WILSON 



REACTION OF TERTIARY AND QUATERNARY NITROGEN 

 DERIVATIVES WITH THE ACETYLCHOLINE RECEPTOR 



Another development which illustrates the value of the 

 study of molecular forces for a better understanding of cellular 

 function is the remarkable difference between the reaction of the 

 proteins of the acetylcholine system to tertiary and that to 

 quaternary nitrogen derivatives. 



In the esterase studies it was in general found that there 

 was not a very pronounced difference in the binding of tertiary 

 and quaternary ammonium ions, but that in the case of sub- 

 strates and nerve gas reactivators there was a much greater 

 promotion by the anionic site. In other words, the extra methyl 

 group seems to increase greatly the functional activity. Owing 

 to a favorable entropy of activation the formation of acetyl 

 enzyme proceeds about 10 times faster with acetylcholine as 

 substrate than with the tertiary ester (45). The same increase 

 in functional activity is observed with choline acetylase : choline 

 is acetylated about 12 times as fast as dimethylethanolamine 



(3). 



The interaction of cell receptors (probably proteins) with 

 applied substances, receptor activators, and receptor inhibitors, 

 might be expected to obey the law of mass action (5,15,41). 

 Having only a limited number of interaction features, acetyl- 

 choline must interact with the receptor in much the same way as 

 with the enzyme and we may, therefore, infer a marked simi- 

 larity in the action sites of both proteins. The hydrolytic 

 process will, of course, be absent. In its place will be the 

 receptor function. Therefore, much that has been learned 

 about the binding forces and such features of specific inter- 

 action as "promotion" may well find their counterpart with the 

 receptor. Receptor inhibitors would be expected to be bound, 

 but the inhibitor lacks those special features which are necesary 

 to bring about the process whereby the receptor functions. As 

 in the case of enzymes, where poorer substrates serve as inhibi- 

 tors, poorer receptor activators under suitable circumstances 

 may be receptor inhibitors. We are thus in a position to apply 



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