VOL. 12 (1953) CHOLINE ACETYLASE SPECIFICITY 32I 



as acetylcholine, has only a severly limited number of features which may contribute to 

 its interaction with proteins. The elementary interactions between the atoms, or groups 

 of atoms, of the ester and the enzyme are intrinsically weak. A relatively strong inter- 

 action is effected by the sum of all or nearly all elementary interactions. All proteins 

 which specifically interact with acetylcholine (or choline) must utilize most of the same 

 elementary interactions and therefore be similarly constituted at the site of action. The 

 exact consequence of the interaction may be determined by the omission of one or more 

 of the elementary interactions or by the addition of repulsive forces, e.g. steric inhibitions 

 peculiar to the particular protein. 



The comparative specificity of the three proteins toward the acid moiety of appro- 

 priate compounds is shown in Table III. In the case of the acetylase the compounds are 

 CoA derivatives and choline is the acyl acceptor. Choline derivatives are the compounds 

 for the esterase and receptor. Enzyme specificity is indicated in two categories : 



a. overall catalytic proficiency 



b. binding strength of the enzyme-substrate complex. 



TABLE III 



Acetylase Esterase 



Acidic moiety . , Receptor 



a b a b 



a. catalytic proficiency. 



b. binding strength 



The two enzymes clearly show a parallel interaction pattern in both categories. In 

 comparing the receptor to the enzymes it is significant that the receptor has no cata- 

 lytic function and, therefore, only comparison of the binding strength of the enzyme with 

 receptor response may be pertinent. Binding to the receptor is a necessary but not a 

 sufficient condition for the response of the receptor. Again there is a strong parallelism 

 except for the benzoate. Whether the weak response of the receptor to the benzoate is 

 real or caused by secondary phenomena is not known. 



The comparative specificity toward the extent of methylation is indicated in Table 

 IV. The compounds tested with the acetylase are the aminoethanols using acetyl CoA 

 as the acyl donor. The three categories of reaction considered for the esterase are 



a. overall catalytic proficiency 



b. substrate inhibition, usually attributed to the formation of an inactive ESg 

 complex 



c. reactivation of tetraethyl pyrophosphate inhibited enzyme^^'^^.The inhibited en- 

 zyme is a diethyl phosphoryl enzyme and its reactivation is an enzymic process. 



The ji5-aminoethyl acetates are the compounds for the esterase categories a and b and 

 for the receptor. The amino alcohols are the compounds for category c of the esterase. 

 As with the acidic moieties there is a marked parallelism in the interaction of these 

 compounds with the three proteins. In all but one instance the removal of a methyl 

 group from the trimethyl derivative results in a very great diminution of interaction. 

 To illustrate this fact just a few examples may be given. If a methyl group is removed 



References p. 324. 



