34 II. DIGESTION AND ABSORPTION OF FATS 



CH 3 COOCH2CH 2 C(CH 3 ) 2 CH 3 ) had the highest rate of hydrolysis of any 

 simple aliphatic ester tested. 



Corresponding specificity or non-specificity has been reported for the 

 cholinesterases from tissues other than blood. Thus, brain cholinesterase 

 has been shown to be of the "true" type, 186 while that prepared from dog 

 pancreas resembled that of the serum {i.e., the pseudo variety). 211 



c'. Inhibition of Cholinesterases : (a') General Description of Inhibitors. 

 — The most characteristic property of cholinesterase is the ability of a large 

 number of compounds to inhibit its action. One of the best known in- 

 hibiting agents is eserine, or physostigmine. This is an alkaloid derived 

 from the seeds of the Physostigma venenosum, or deadly Calabar bean. 

 The empirical formula is C16H21O2N3, and it has the following structure 

 shown below: 



H 

 H 3 C O C CH 3 



\ Jl ^\ X 



. N— C— O— C C C CH 2 



/ I II I I 



H HC C C CH, 



\y \ /\\ / 



C N H N 



CH 3 CH 3 

 Eserine or Physostigmine 



The specificity of the action of eserine in potentiating the effect of stimu- 

 lation of cholinergic nerves was proved by Dale and Gaddum 212 in their 

 studies of denervated voluntary muscles. These authors conclude that 

 "the effects of eserine further limit our choice ... (of a chemical trans- 

 mitter) to a choline ester readily hydrolyzed by the tissues. Acetylcholine, 

 the only choline ester which has been shown to exist in the animal body, is 

 preeminent in physiological activity . . . and in its liability to the hydrolytic 

 destruction which eserine specifically inhibits." It is now generally con- 

 sidered that the eserine effect on cholinesterase is so specific that a powerful 

 induction of a nerve impulse by this drug is an evidence that acetylcholine 

 plays a role in the transmission of this impulse. Eserine forms salts with 

 most of the common acids. 



In addition to eserine, and the several compounds listed in Table 2, 

 many other substances are known to act as inhibiting agents for cholin- 

 esterases. These have been classified by Ammon 166 into the following 5 

 groups listed in Table 3. 



211 B. Mendel and D. B. MundeU, Biochem. J., 37, 64-66 (1943). 



212 H. H. Dale and S. H. Gaddum, /. Physiol, 70, 109-144 (1930). 



