286 



6. INTERACTIONS OF INHIBITORS WITH ENZYMES 



further methyl groups reduces the binding energy; the average reduction 

 per methyl group is 1.14 kcal/mole. Wilson interpreted this energy dif- 

 ference as due to dispersion forces between the methyl groups and the pro- 

 tein. However, Bernhard (1955) calculated that this is about 0.7 kcal/mole 

 more than expected from dispersion forces. Using Eq. 6-17, the dispersion 

 energy for interaction of a methyl group with protein is — 0.58 kcal/mole, 



Table 6-22 

 Ion-Ion Interactions for True Cholinesterase " 



Compounds tested 



(1) Nicotinamide and 

 iV-methylnicotinamide 



(2) Isoamyl alcohol and 

 dimethylethanolammonium 



(3) 3,3-Dimethylbutyl acetate 

 and acetylcholine 



(4) Physostigmine at pH 6 

 and pH 10 



(5) Dimethylaminocthyl acetate 

 at pH 6 and pH 10 



(6) ChoHne on true and 

 pseudocholinesterase 



(7) Tetramethylamnioniuin ion 

 on true and pseudocholin- 

 esterase 



(8) Tetraalkylammonium ions 

 extrapohited to tetra- 

 methyhininioniuin ion 



Calculated equihbrium 

 distance 



Vahies in 

 Uterature 



(A) 



5.8 

 5.0 

 5.6 

 6.6 

 6.6 

 6.5 

 5.4 



6.5 



(5.3) 



From Eq. 6-85 



n = 1 



(A) 



(6.6) 

 Averages 



6.15 



5.15 



6.15 

 5.38 

 5.55 



5.38 



5.17 



5.45 



5.60 

 5.55 



7.83 



6.65 



7.83 

 7.00 

 7.17 



7.00 



6.67 



7.05 



7.40 



7.18 



Ref." 



(a) 

 (b) 

 (c) 

 (b) 

 (c) 

 id) 

 (a) 



id) 



(e) 



(/) 



(/) 



" Kg/K^ is the ratio of the dissociation constants of tlie substrates or inhibitors 

 used and n is the number of anionic groups assumed on the enzyme site. The vahies 

 of dg from the literature include correction for the ion atmosphere except for those in 

 parentheses. The values oid^ in the last two columns were estimated from Fig. 6-17. 

 The AF in (8) is for one anionic group, inasmuch as the total interaction energy was 

 determined and a value of n = 2 was assumed. 



* References: (a) Wilson (1957), (6) Wilson (1952 a), (c) Bernhard (1955), {d) Wilson 

 and Bergmann (1950), (e) Adams and Whittaker (1950), (/) Bergmann (1958). 



