Specificity in Cholinest erase Reactions 



I. B. Wilson 



Columbia University, New York City, N. Y. 



IN TALKING ABOUT THE SPECIFICITY of choliiiesterase reactions, I will have 

 to include older work and I want to apologize to those of you who will 

 have to listen to this again. The substrate for cholinesterase is acetyl- 

 choline. It is a quaternary amonium ion and it is also an ester. The reaction 

 is a hydrolysis to form the quaternary amino alcohol choline, and acetic 

 acid. O 



II 

 (CH3)3NC2H40— CCHs + H2O -^ (CH3)3NC2H40H + CH3COOH. 



The way one usually writes an enzyme catalyzed reaction is 



E + S . ' ' E • S ^"' > E + products 



so that, assuming a stationary state in E.S., 



V = 



where 



Km = 



K,E' 



Km + 5 



k2 + ks 



h 



Now, when we say that a compound is a good substrate, we mean that it is 

 hydrolyzed at a high rate, at a low substrate concentration. That means that 

 besides having a good value for k^ , the ]Michaelis-^Ienten constant. A',,, , must 

 be quite small. 



The first thing is to find out from the specificity of the reaction what forces, 

 what factors, are involved in making Km small. Now, this interpretation of 

 the Michaelis-Menten constant includes both an equilibrium term and a kinetic 

 term in which k-i over ^1 is the equilibrium dissociation constant for the enzyme 

 substrate complex. It is clear that Km has to be greater than or equal to the 

 dissociation constant and, since we want Km to be small, we have to have a 

 small dissociation constant. 



From the structure of this substrate, I think one would suspect that if the 

 forces of nature had designed a protein to combine with such a molecule it 

 certainly would have taken advantage of ionic forces and I would suspect that 



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