540 ANNALS NEW YORK ACADEMY OF SCIENCES 



the pattern of certain of the cholinesterases may be made, it will be 

 shown that there are a number of exceptions to any strict classification. 



Easson and Stedman^' proposed the following criteria for the specific- 

 ity of the cholinesterase action of different sera: (a) relative action of 

 the serum on choline and non-choline esters; (b) inhibition of the ester- 

 splitting action by prostigmine; (c) hydrolysis of mixed substrates. 

 Thus, human serum was considered to contain a specific cholinesterase, 

 because its action on non-choline esters was about l/80th of that to- 

 wards butyrylcholine, and because both actions were inhibited to the 

 same extent by the same concentration (10"'' M) of prostigmine. On 

 the other hand, guinea pig serum was considered to contain a specific 

 cholinesterase and a non-choline, ester-splitting esterase; because the 

 rate of actions on butyrylcholine and methylbutyrate were of about the 

 same magnitude; because 10~^ M prostigmine inhibited, markedly, only 

 the action on butyrylcholine; and because the actions on a mixture of 

 butyrylcholine and methylbutyrate were equal to the sum of the action 

 on each. We have found that judgment as to the relative action of a 

 serum or tissue extract on acetylcholine and non-choline esters may de- 

 pend considerably on the particular esters employed. For example, if 

 the actions of human and rabbit brain extracts on acetylcholine are 

 compared with that on monoacetin, it is found that there is relatively 

 little hydrolysis of the latter. It might be concluded that these extracts 

 contain, chiefly, specific cholinesterase. On the other hand, if the ac- 

 tion is compared with that on triacetin, it is found that there is consid- 

 erable hydrolysis of this ester, and it might just as readily be concluded 

 that the content of non-specific esterase is very high. 



Mendel and Rudney^^ stated that there were two different cholin- 

 esterases in the body : one of which acted exclusively on choline esters ; 

 and the other, a non-specific enzyme, which split both choline and non- 

 choline esters. These they termed "true" and "pseudo"-cholinesterases, 

 respectively. In addition to some of the criteria for specificity em- 

 ployed by Easson and Stedman,*^ Mendel and Rudney^^ pointed out 

 that the non-specific or "pseudo"-cholinesterases exhibited maximal ac- 

 tivity at high concentrations of the substrate, acetylcholine, whereas 

 the "true" cholinesterase showed optimal activity at low substrate con- 

 centrations. According to these authors, inhibition of both choline 

 and non-choline ester hydrolysis constitutes a criterion for distinguish- 

 ing the cholinesterase as "pseudo." We have found that the anti- 

 cholinesterase compound, DFP, markedly inhibits the mouse brain 

 hydrolyses of both acetylcholine and triacetin. According to the cri- 

 teria of Mendel and Rudney, this finding should classify mouse brain 



