DAVID NACHMANSOHN AND IRWIN B. WILSON 



electrolyte distribution. The energy for this "active" ion trans- 

 port must be assumed to be provided by the chemical energy 

 derived from reactions common to most cells. 



The Proteins of the Acetylcholine System 



Once the integration of acetylcholine into the metabolic 

 pathways of the neuron had been accomplished, by 1950, the 

 mechanism of the elementary process and the interaction of 

 acetylcholine with the specific proteins of the system became of 

 primary interest. To a certain extent the situation resembled 

 that in muscle physiology, when biochemical studies in the late 

 thirties had resulted in the recognition that ATP is the primary 

 energy source in the elementary process of contraction and the 

 properties of myosin and actin and their reactions with ATP 

 began to dominate muscle research. In the case of nerve the 

 situation is somewhat different: of the four proteins reacting 

 with acetylcholine directly, only the two enzymes, the esterase 

 and the acetylase, are available for studies in vitro. In contrast 

 to the situation in muscle physiology the receptor is not available 

 in solution ; its reactions may be tested in intact structures only. 

 Nothing is known about the storage protein. 



ACTIVE SURFACE OF ACETYLCHOLINESTERASE; 

 THE HYDROLYTIC PROCESS 



The most suitable protein for studying the molecular forces 

 responsible for interaction with acetylcholine is the esterase. 

 This is due to its stability and great reactivity with a large variety 

 of compounds. However, information obtained with this 

 enzyme might be of considerable value in understanding the 

 reactions with the other proteins of the system. A molecule such 

 as acetylcholine has only a limited number of features which 

 may contribute to its interaction with proteins. All proteins of 

 the system reacting specifically with the ester must do so through 

 the same elementary interactions. We may, therefore, assume 

 that they are similarly constituted at the active site. Small dif- 

 ferences might lead to a considerable alteration of function. 



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