462 THE BIOCHEMISTRY OF B VITAMINS 



to the biological system, a decreased rate of coenzyme formation would 

 be essential to maintain the defined response. To decrease the rate of 

 coenzyme formation, an increase in the inhibition index is required such 

 that another enzyme system, e.g., E C) requiring the coenzyme becomes 

 the limiting system of the biological process. There is a definite order 

 in which the secondary products exert their effects. If a biological system 

 is somewhat deficient in a secondary substrate, e.g., S a , when the conver- 

 sion of this substrate to product, P a , is the limiting reaction of the system, 

 supplements of this substrate will allow the reaction to proceed more 

 efficiently. To maintain the defined inhibition of the system, the concen- 

 tration of the enzyme, E a , must be decreased by decreasing the rate of 

 coenzyme formation. This necessitates an increase in the ratio of analogue 

 to vitamin. The increase in the inhibition index resulting from such addi- 

 tions will seldom approach that obtained with the product, P a . 



Figure 3. Relationship of Enzymatic Reactions to Inhibition of Coenzyme Formation 

 by Analogues of Vitamins 



Substances which prevent the product of the inhibited enzyme reaction 

 from being utilized in a manner not essential for the biological response 

 would be expected to exert a "sparing action" on the product. Undoubtedly 

 still other types of substances exerting such an action will be discovered. 



(4) Changes in Total Effective Enzyme Concentration. From equa- 

 tion (19) it is apparent that exogenous substances which increase the 

 total effective enzyme concentration, E t , will affect an inhibition in a 

 manner such that an increased ratio of analogue to metabolite is required 

 in order to obtain the same degree of inhibition as in the absence of such 

 substances. Since [ES] is small in comparison with [E f ] and is main- 

 tained at a defined value under these conditions where only [E t ], [I] and 



