DAVID NACHMANSOHN 



The oxidation products of amino acids, i. c, a-keto acids 

 (pyruvic, phenylpyru\'ic, oxyphenylpyruvic, and a-ketoglutaric acids 

 have been tested) have a strong inhibitory effect on the formation 

 of acetylcholine when present in concentrations of 10~' to 10~* molar. 

 These are close to the concentrations w^hich occur in living cells. 

 Pyruvic acid is known to be a "physiological anticonvulsant" (20). 

 The strong inhibitory effect of a-keto acids on the formation of acetyl- 

 choline is therefore obviously of physiological as well as of clinical 

 interest. 



Action Potential and Inhibition of Choline Esterase 



A new and significant relationship has been recently established 

 between enzyme activity and nerve action potential, this time using the 

 peripheral axon as material (Bullock, Nachmansohn, and Rothenberg) . 

 If acetylcholine is the depolarizing agent and if the function of choline 

 esterase is to remove the active ester so that polarization again becomes 

 possible after the passage of the impulse, then inhibition of the enzyme 

 should alter and, in sufficiently high concentration, should abolish the 

 nerve action potential. Experiments carried out on the giant axon 

 and on the fin nerve of squid have shown that eserine, known to be a 

 strong inhibitor of choline esterase, alters and finally abolishes the 

 nerve action potential. When the nerves are put back into sea water, 

 they quickly recover and conductivity reappears. The reversibility 

 of the effect is consistent with the fact that the inhibition of choline 

 esterase is easily reversible in vitro. Strychnine, another inhibitor of 

 choline esterase, was also found to alter and, in higher concentrations, 

 to abolish the nerve action potential reversibly. 



Prostigmine has in vitro the same effect as eserine, but it has no 

 effect on the nerve action potential. Eserine is a tertiary amine and 

 may therefore, if undissociated, penetrate the lipoid membrane. 

 Prostigmine is a quaternary ammonium salt and therefore it cannot 

 penetrate the lipoid membrane. This has been demonstrated experi- 

 mentally: Eserine was found in the axoplasm of nerves kept in a solu- 

 tion containing this compound, while prostigmine was absent in the axo- 

 plasm tested under the same conditions. These observations explain 

 why prostigmine and acetylcholine, both quaternary ammonium salts, 

 act externally only on nerve endings which do not have a myelin 



