CATALYSIS: THE GUIDE OF LIFE 123 



cholinesterase activity and conduction can be demonstrated is based 

 on the effect of cholinesterase inhibitors. If the breakdown of the 

 membrane during the passage of the impulse is connected with the 

 release of acetylcholine and the restoration of the resting condition 

 requires the immediate removal of the active ester, then inhibition of 

 cholinesterase should abolish conduction. It can be shown on a great 

 variety of nerves, that eserine, a strong inhibitor of cholinesterase, 

 abolishes the action potential. The enzyme-inhibitor complex in this 

 case is easily reversible. In agreement with the reversibility of the 

 chemical process, the nerve and muscle action potentials reappear 

 when the eserine is washed out. 



"Recently a new potent inhibitor of cholinesterase became known, 

 namely, di-isopropyl fluorophosphate (DFP). This compound, in con- 

 trast to eserine, destroys cholinesterase irreversibly. The rate of 

 irreversible destruction depends, however, on several factors like tem- 

 perature, concentration, etc. A most striking parallelism can be 

 demonstrated between the rate of destruction of cholinesterase and the 

 rate of abolition of the action potential. The close correlation 

 between the two events can be established as a function of time as well 

 as of temperature. The rate of irreversible inactivation of the enzyme 

 in vitro at a given temperature coincides with the rate of irreversible 

 inactivation of the enzyme and the irreversible abolition of the action 

 potential in nerves. The experiments have established conclusively 

 that the activity of the enzyme is inseparably associated with the con- 

 duction in nerve and muscle. 59 > 60 - 61 



"Prostigmine, another cholinesterase inhibitor, which is in vitro 

 as strong as eserine, has no effect on nerve and muscle conduction. It 

 can be shown on the giant axon of Squid that prostigmine, in con- 

 trast to eserine and DFP, does not penetrate the lipoid membrane sur- 

 rounding all nerves (whether myelinated or unmyelinated). 62 Prostig- 

 mine is, like acetylcholine and curare, a methylated quaternary am- 

 monium salt. Such compounds are not soluble in lipoids. This may 

 explain why these compounds act only on the nerve endings where no 

 lipoid membrane is found, but do not affect muscle or nerve fiber. 

 The peculiar ability of the synapse to react to certain compounds, as 

 first demonstrated for curare by Claude Bernard, was the basis for the 

 assumption of a special mechanism for the propagation of the impulse 

 across the synapse. In the light of recent biochemical and biophys- 

 ical findings, this peculiar ability may be attributed to a difference in 

 the anatomical structure rather than the underlying basic mechanism. 

 Recent observations of Arvanitaki, Bullock, Eccles and others, support 

 the assumption that the flow of current is the propagating agent 

 across synapses, as it is along the fibers. In the pre- and post-synaptic 



