130 4. SUBSTRATE INHIBITION AND PRODUCT INHIBITION 



the inhibition is due to interference with DPN+ binding since the steroid 

 and DPN+ must bind close together because of the stereospecificity in the 

 hydrogen transfer. 



Maximal rates for pig kidney aminoacylase were obtained at different 

 concentrations with various substrates (Mounter et al., 1958). Although 

 there are not enough substrates to make any detailed correlations with 



structure, the fall in (Sq) with a lengthening of the hydrocarbon side-chain 

 would indicate that this part of the molecule is at least involved in the 

 binding to the site of inhibition (see tabulation). 



Combination of Substrate with an Activator (Type C) 



Enzymes requiring metal ion activators may show substrate inhibition 

 since their substrates often have carboxylate or phosphate groups which 

 can complex or chelate with the metal ion. Indeed, it is generally believed 

 that metal ions function as activators because of their ability to bind the 

 substrate, wholly or in part, to the enzyme. Whether inhibition of this 

 type will or will not occur depends on the binding of the activator to the 

 enzyme: if the activator is primarily bound to the substrate (i.e., if the 

 true substrate is a complex with the activator) no inhibition will occur at 

 high substrate concentrations due to activator de])letion, but if the acti- 

 vator is attached primarily to the enzyme, such depletion may occur. These 

 two situations may be represented as follows: 



Type C inhibition absent 



S + A^ AS 

 E + AS^ EAS -^ E + A + P 



Type C inhibition may occur 

 E + A;^ EA 

 EA + S^ EAS -> EA + P 



S + A^ AS 



