COMPETITIVE ANALOGUE-METABOLITE INHIBITION 461 



(3) "Sparing Effect" on the Product. The following equation can be 

 obtained by solving equation (4) (p. 446) for [EI\ and substituting the 

 value in equation (3) (p. 446). 



[I]_ Kj([E t ]-[ES]-[E]) 



[S] K S [ES] Uy; 



If exogenous substances act in such a manner as to decrease the amount 

 of product, P, necessary for a constant response of the biological system, 

 the concentration of the enzyme-substrate complex must be decreased 

 accordingly, to maintain a defined response of the system in the presence 

 of such substances. This can be accomplished by increasing the ratio of 

 inhibitor to substrate. Since [E] is relatively small and can be neglected, 

 and since [E t ] is relatively constant and is large with respect to \ES] 

 under the testing conditions, it is apparent from equation (19) that the 

 inhibition index varies approximately inversely with [EJS], which is 

 defined by the amount of product necessary for the defined response of 

 the biological system. Consequently, the decrease in the amount of product 

 required by the biological system for a constant response as a result of 

 the addition of substances exerting a "sparing action" is reflected by a 

 proportional decrease in [ES] , and a practically proportional increase in 

 the inhibition index. 



If the product, P, of the inhibited enzyme system is involved in the 

 biosynthesis of secondary products, P a , P b , P c , etc., these secondary 

 products can exert an effect on the inhibited biological system. If a sec- 

 ondary product is formed by a reversible reaction and if the reverse 

 reaction can take place under the testing conditions, the secondary product 

 will affect the inhibition in a manner analogous to the primary product. 

 However, in many instances the secondary products cannot form the 

 primary product by a reversible reaction. In such cases, one particular 

 secondary product would be expected to become the substance limiting 

 the biological response, and would be capable of exerting a "sparing 

 action" on the primary product. A definite order in which the secondary 

 products exert their effects would be expected. 



While analogues of vitamins may in some cases inhibit at the coenzyme 

 stage, analogues often prevent coenzyme formation from the vitamin, as 

 illustrated in Figure 3. The coenzyme in turn is required by several 

 apoenzymes to form a series of enzymes, E a> E b , E c , etc. These apoenzymes 

 vary in their relative concentrations and in their affinity for the coenzyme, 

 and the enzymes are required by the biological system in different con- 

 centrations. Consequently, one particular enzyme system, e.g., E a , requir- 

 ing the coenzyme would be expected to become the limiting factor of 

 the biological system. If the product, P a , of such an enzyme is supplied 



