PRODUCT INHIBITION 147 



The 1:)inding of product to its site prevents the reaction ES -> EP but does 

 not necessarily prevent the binding of tlie substrate so that the complex 

 ESP occurs. Noncompetitive kinetics will be given by this system and it 

 is possible that many of the instances of product inhibition fall into this 

 category. 



Product Inhibition in Multienzyme Systems 



In a sequence of reactions catalyzed by a series of enzymes, the product 

 of any step may inhibit an enzyme earlier in the sequence rather than the 

 one responsible for its formation. Such a mechanism may exert a self- 

 regulatory control on the over-all rate. One of the final products of pyrimi- 

 dine synthesis is cytidylic acid and this inhibits the first reaction in the se- 

 quence (Pardee, 1959); thus the synthetic rate is controlled by the accu- 

 mulation of this product. In systems of any degree of complexity, product 

 inhibition may be a major factor in rate regulation and particularly within 

 the cell this may contribute to the metabolic organization. 



The degree of inhibition exerted by a product depends on the level of 

 concentration reached and hence on both the rate of its formation and the 

 rate of its disappearance. A product may either diffuse away from the en- 

 zyme it inhibits or it may be further altered by another enzyme. In a steady 

 state the product concentration will remain constant and exert a constant 

 inhibition. If now another inhibitor is introduced there are two ways in 

 which the system may be affected. If the inhibitor acts on the enzyme 

 forming the product, the product concentration will decrease and the 

 inhibition exerted on this enzyme will be lessened; thus the inhibition caused 

 by the added inhibitor will be less than expected on the basis of no pro- 

 duct inhibition. Or the inhibitor may act on the enzyme that destroys 

 the product, in which case the product concentration will rise and the 

 inhibition will be greater than would have been exerted by the added 

 inhibitor alone. The steady-state concentration of product in the follow- 

 ing system: 



k 

 K, El + S^EiS -^Ei + P 



K^ Ei+P — EiP (4-47) 



K^' E, -f P— E.P^E, +Q 



may be determined by the equation: 

 d(?) 



(It 



^•i(EiS) - A-,(E,P) = (4-48) 



The expression for (P) will be quadratic and will depend on the type of 

 product inhibiton. For competitive inhibition: 



