NERVOUS ACTION 



found in the giant axon l:)y Cole and Curtis (3) and in the electric 

 tissue by Cox, Coates, and Brown (4), suggests that the paralleMsm 

 foinid between voltage and acetylcholine metabolism may be due 

 essentially to the effect of the ester on permeability in the way outlined 

 above. 



Specificity oj the Enzyme. In all the experiments on the activity 

 of the enzyme, it was assumed that choline esterase is specific for 

 acetylcholine. In such a case, not only is the conclusion justified 

 that the substrate metabolized is acetylcholine, but the activity of a 

 specific enzyme determined in vitro may well be used as an indicator 

 for the rate of the substrate occurring in vivo. As pointed out by 

 Schoenheimer and Rittenberg (21), one of the most important general 

 results of the work with isotopes is the conclusion that "enzymes do 

 not lie dormant during life but are continuoiasly active." This, of 

 course, does not imply that all enzymes are working at an optimal rate 

 at every moment. In cells Uke nerve and muscle a considerable 

 difference must be expected between resting condition and a state of 

 activity. Lactic acid formation for instance, occurs in anaerobic 

 condition even in the resting muscle; but during tetanic stimulation 

 the rate increases several thousand times. Siinilaily, it cjumot be 

 expected that an en/.yme directly connected with the events during the 

 passage of the impulse is equally active in resting condition. It ap- 

 pears possible, moreover, and even probable, that enzymes are, to 

 some extent at least, present in excess above the optimum usually re- 

 quired. But all experience in enzyme chemistry appears to indicate 

 that a correlation exists between the concentration of an enzyme in a 

 cell and the rate at which the substrate is metabolized. 



It thus appeared imperative to demonstrate the specificity of 

 the enzyme. The ester linkage in acetylcholine shows no peculiar 

 properties. It is therefore to be expected that this ester can be hy- 

 drolyzed by other esterases and, on the other hand, that choline 

 esterase can hydrolyze other esters. Specificity in this case would be 

 expected, on the basis of analogy, to be only relative and not absolute. 

 Choline esterase might be expected to split acetylcholine at a higher 

 rate than other esters, while other esterases might be expected to 

 behave diff'erently. By testing a number of substrates a pattern has 

 been established which makes it possible to distinguish choline esterase 

 from other esterases (17). 



343 



