DAVID NACHMANSOHN AND IRWIN B. WILSON 



(43). Analysis of the postulated equilibria and relations which 

 were borne out by experiment led Wilson to the calculation of 

 the /?K's of the basic and acidic groups in the esteratic site of the 

 enzyme surface. Figure 2 represents a scheme, illustrating the 

 interaction between acetylcholinesterase and its substrate. 



On the basis of these studies Wilson proposed the following 

 mechanism of hydrolysis : 



H^G® G® 



.3^1 II 



H-G + CHqCOOR =f=^ R-O7-C-O® »► C-O® + ROH 



CH3 CH3 



(A) (B) 



H G® H-G® 



I II I 



H-O: + C-O® ^==^ HO-C-O® =?=^ H-G + CH3COOH 



I I 



GH3 CH3 



(C) 



Here H — G represents the esteratic site of the enzyme bearing an 



acidic group (H) and a basic group (..). Intermediate (B) is a 

 resonance form of acetyl-enzyme. (A) and (C) are Michaelis- 

 Menten complexes. The proposed mechanism has been verified 

 in a variety of ways (33,34,44). 



In the last few years, the mechanism of enzymatic action and 

 the analysis of molecular forces acting in this process, as was 

 outlined here for acetylcholinesterase, has increasingly pre- 

 occupied biochemists, supplementing the study of metabolic 

 pathways. This development parallels in a certain way the 

 studies of structural proteins such as actin and myosin. The 

 results of these investigations are beginning to contribute to our 

 understanding of cellular function on a molecular level, al- 

 though, as will be discussed below, there are still many gaps be- 

 tween the in vitro studies and the phenomena observed in intact 

 cells ; the greatest obstacle is undoubtedly the lack of knowledge 

 of ultrastructure. In the following, two developments may be 



638 



