INHIBITION OF ENZYMES 619 



write the various possible reactions which may occur between the different 

 arsenicals and enzymes: 



/S-E 



A. R— As=0 + HS-E •* » R— As' 



S-E 



B. R— As = + 2 HS— E • * > R— As + H.O 



^S-E 



C. R.,=As— CI + HS— E "* > R_,= As — S— E + HCl 



+ H.,0 



HCI 



It is generally considered that reactions C and D represent the mechanisms 

 by which potent inhibition is produced. It is not known whether reaction A 

 can occur, but if it does it probably by itself does not lead to a very tight 

 binding, at least relative to the cyclic thioarsinite formed in reaction D. 

 Reaction B appears to be unlikely because of steric and electrostatic factors 

 in holding two protein molecules when the bond angle from arsenic is fixed. 

 Reaction F should become more and more unlikely as the R groups become 

 larger or more charged, again because of steric and electrostatic factors, 

 providing the SH groups are close together as is assumed here. Thus we 

 are left with reactions C, D, and E as being the most important for potent 

 inhibition of enzymes in general. The following points may now be made. 



(1) Potent inhibition by R — As=0 would not be adequate evidence 

 for a dithiol since other factors might be involved. Oxophenarsine, for 

 example, might inhibit well due to electrostatic forces or hydrogen bonds 

 from the amino or hydroxy groups to the enzyme, as well as less specific 

 forces between the benzene ring and the enzyme, which might stabilize a 

 complex such as that formed in reaction A. Of course, the problem always 

 arises as to exactly what should be considered a potent inhibition; e. g., 

 some workers have argued for SH groups on the basis of moderate inhibi- 

 tion by arsenicals at 1-10 mM, whereas Dawson (1956 b) stated that phos- 

 pholipase B probably contains no important SH groups despite a 44% 

 inhibition by 0.5 mM (p2=-^s, — CI (it is interesting that iodoacetate and 

 p-MB do not inhibit well but Hg++ does). 



