PRODUCT INHIBITION 145 



Many phosphorylation reactions involving ATP are inhibited by ADP but 

 in most cases the type of inhibition is not known. Pyridoxal phosphokinase 

 is inhibited competitively by ADP (Hurwitz, 1953) as is glutathione syn- 

 thetase (Yanari et at., 1953); in the latter case ADP appears to be bound 

 more tightly than ATP to the enzyme. Indeed, the ATPases from various 

 sources are inhibited weakly by ADP (Kielley and Kielley, 1953; Blum, 

 1955). 



Enzymes catalyzing the acylation of amino groups: 



R-COSCoA + HjX-R' -^ R-COXH-R' ^ CoASH (4-41) 



such as the arylamine transacetylase (Tabor et al., 1953) and glycine trans- 

 acylase (Schachter and Taggart, 1954) of liver are inhibited by coenzyme A. 

 The inhibition is not a function of the SH group because reaction of the 

 CoASH with iodoacetate does not reduce the inhibitory activity. When 

 benzoyl-CoA is used as the acyl donor, glycine transacylase catalyzes 

 the formation of hippurate, which is also inhibitory; 50% inhibition is 

 given by 0.58 niM hippurate and 0.65 milf CoASH. The free energy change 

 for this reaction of approximately — 8 kcal/mole indicates the inhibition 

 if of type B, as does the inhibition by single products. The inhibition is 

 noncompetitive with respect to both benzoyl-CoA and glycine according 

 to reciprocal plots. Finally, the inhibition by hippurate depends on the 

 acyl donor, only about one-twentieth of the concentration required for 

 50% inhibition being necessary for acetyl-CoA compared to benzoyl-CoA. 

 It is difficult to reconcile these data with any detailed mechanism unless it 

 is assumed that the hippurate combines with a group adjacent to the active 

 center and interferes in some manner with the transacylation process. 

 The inhibition of urease by NH+4 presents somewhat different problems 

 (Hoare and Laidler, 1950). Here there are two sites at which urea can be 

 bound although reaction occurs when urea is bound to one site and water 

 to the other. The rate equations developed for the various possibilities are: 



(S') 

 Uninhibited reaction: v = V,„ 



Noncompetitive inhibition: v, = V„ 

 Competitive inhibition: 



Inhibition at one site: v,- = F„ 



Inhibition at both sites: t', = F„ 



By plotting v/v^ against (I) it was shown that the inhibition was non- 

 competitive. Since deviations from the expected behavior did occur at 



