DAVID NACHMANSOHN 



appropriate conditions, their activity is suitable for investigation. 

 Moreover, study of cellular constituents as such does not indicate which 

 changes they may undergo in the living cell and at what rate. It is 

 true that study of an isolated enzyme alone does not yet permit direct 

 correlation with its cell function, since there are so many simultaneous 

 reactions in the complex system of the living cell. But, by investigating 

 a great number of reactions and series of reactions, and by studying 

 their connection with events in the intact cell, valuable information 

 of the chemical mechanism of cell function may be obtained. One 

 of the most conspicuous examples of such an analysis is the development 

 of muscle physiology. Because of the pioneer work of A. V. Hill and 

 O. Meyerhof, many physical and chemical changes have been cor- 

 related; and our concept of the mechanism of muscular contraction 

 has gone through a real "revolution," according to an expression of 

 A. V. Hill, although we are still far from having a complete picture. 



The most promising approach to the chemical reactions in- 

 volved in nerve activity appears, therefore, to be by way of a study of 

 the enzymes involved. Since Loewi's discovery suggested that the 

 release of acetylcholine may be connected with the transmission of 

 the nerve impulse, it could be expected that a study of the enzymes 

 involved in the formation and hydrolysis of the ester might lead to the 

 elucidation of the precise role of acetylcholine. 



But even the best methods of enzyme chemistry available are 

 not adequate for the study of many problems. In many cases, in order 

 to find a satisfactory answer, it was necessary to combine enzyme 

 chemistry with the selection of special cases which offered particularly 

 favorable conditions for the different problems. 



Role of Acetylcholine 



Investigations based on this line of approach and carried out 

 over a period of nearly ten years have provided evidence for a new 

 concept of the role which acetylcholine may have in the mechanism 

 of nervous action (7,11). According to the new concept, the release 

 and the removal of the ester are considered as an intracellular process 

 occurring at points along the neuronal surface and directly connected 

 with the nerve action potential. 



The action of acetylcholine may be pictured in the following 

 way: The nerve is, according to the generally accepted "membrane 



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