BOD AN SKY: CHOLINESTERASE 525 



esterase and dialyzed horse serum cholinesterase. Ba"^"^ activates Tor- 

 pedo cholinesterase, but not dialyzed horse serum cholinesterase. 



There has been considerable disagreement, regarding the activating 

 effects of Na+ and K"". But here, as in other respects, these disagree- 

 ments are resolved, if it is recognized that the studies have been carried 

 out on cholinesterases from various sources. Thus, 1 X 10~^ MK"" 

 inhibits Mendel and Rudney's purified horse serum cholinesterase 40 

 per cent at a substrate concentration of .0015 M acetylcholine, 15 per 

 cent at .03 M.^^ Glick-^ found, at .02 M substrate concentration, 

 that Na+ and K+ did not have any regular effect on horse serum cholin- 

 esterase activity, but both increased rabbit serum cholinesterase activ- 

 ity 25 per cent at 0.3 M Na+ or K+, 35 per cent at 0.5 M, and 40 per 

 cent at 1.0 M. Nachmansohn^^ reported that both Na"" and K+ activ- 

 ated Torpedo cholinesterase. 



There appears to be a relationship between the effect of Na* and K"" 

 and the effect of substrate concentration on reaction velocity. Thus, 

 in human serum where the substrate-reaction velocity relationship fol- 

 lows the Michaelis-Menten formulation, 0.16 M NaCl inhibited the 

 cholinesterase about 10 to 20 per cent, at substrate concentrations 

 ranging from 1 X lO"** to 4 X 10~*. On the other hand, among red cell 

 cholinesterases, in which reaction velocity decreases at higher substrate 

 concentrations (Haldane formulation), 0.16 M NaCl, inhibited at low 

 substrate concentrations, activated at substrate concentrations greater 

 than about 1 X 10"^'^ M. Alles' and Hawes' results" show, and Mendel 

 and Rudney^'^ have emphasized this point particularly, that, for those 

 cholinesterases which follow the Haldane formulation for the relation- 

 ship between substrate' concentration and reaction velocity, the presence 

 of Na"^ or K"" not only increases the value of the optimal reaction rate, 

 but also shifts the optimum to higher substrate concentrations. 



So far as anions are concerned, cyanide has been found to have no 

 effect on horse or human serum cholinesterase. Oxalate, fluoride, and 

 citrate inhibit dialyzed horse serum cholinesterase to the extent of 30 

 per cent at 0.002 M concentrations of these ions, 60 per cent at 

 0.02 M.^" 



INHIBITION OF CHOLINESTERASE ACTIVITY 



■ The inhibiting effects of various compounds on enzyme activity have 

 been generally formulated in terms of an inactive, but reversible, 

 enzyme inhibitor complex.^' ^ If the inhibition is non-competitive, then 



v' K, 



V K, + I 



(3) 



