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L. J. MULLINS 



3 



Fig. 11. Possible arrangements of anionic (A), and esteratic (E) sites as described 

 in the text. 



with only one of the membrane molecules. Thus, TMA should interact with 

 two membrane molecules and enough space should be left in the interspace to 

 accommodate thiolacetic acid; this is possible in the arrangement shown in 

 Fig. 12. The greater asymmetry of TEA suggests that it will not approach any 

 of the A sites as closely but that its binding by dispersion forces will be of im- 

 portance. In the interspace ACh is shown in two orientations, one for enzyme 

 and one for receptor action. Just which of these two arrangements will be 

 favored depends upon the interspace size; in the diagram a small interspace 

 (2 A separation) is shown, and hence the 'enzyme' orientation is not a good fit. 

 Certain features of the action of specific inhibitors of ACh-ase are helpful in 

 testing the general validity of the arrangement of specific sites in the interspace. 

 With TEPP, the anionic site is functional, while it is not with DFP (Wilson 

 et al, 1955). Again, the action of eserine and neostigmine is contrasting in that 

 the latter substance depolarizes. The fluorophosphate DFP also differs from 

 eserine in that it can fit into an interspace of a size similar to those previously 

 considered (2 A. separation) while eserine and prostigmine require larger sized 



