140 4. SUBSTRATE INHIBITION AND PRODUCT INHIBITION 



PRODUCT INHIBITION 



The products of a reaction can slow down the forward rate in two gen- 

 eral ways. 



A. The reverse reaction, whereby the products are transformed into the 

 substrate, competes with the forward reaction so that the measured rate 

 of substrate disappearance or product formation is reduced. Inasmuch as 

 most enzymes catalyze reversible reactions this type of product inhibition 

 is theoretically very common; it is practically uncommon because in most 

 reactions the equilibrium is far to one side and the reverse reaction is in- 

 significant. 



B. A product of the reaction can combine with the enzyme, or other 

 component of the system, so that the forward rate is inhibited. In this 

 case the product may inhibit by any of the mechanisms discussed in the 

 previous chapter. The primary difference between these two mechanisms 

 of inhibition is that in the former situation the product reacts with the 

 enzyme in such a way as to form a reactive complex, i.e., it combines with 

 the active center to form the same complex in the activated state as is 

 formed from the substrate, whereas in the second type the complex of en- 

 zyme and product is inactive and may be located at the active center or 

 vicinal to it. 



When the reaction is started with only substrate present, product inhi- 

 bition is seldom of importance if only initial rates are measured or obtained 

 by extrapolation. However, if the equilibrium is in favor of the substrate 

 or the product is a relatively potent inhibitor of type B, measurements 

 made over arbitrary intervals of time may provide rates which are only 

 average values over this interval and from which incorrect values for the 

 constants of the enzyme reaction are obtained. These errors may be cir- 

 cumvented if it is first established that the rate is constant over the ex- 

 perimental interval employed. 



Inhibition by the Reverse Reaction 



The over-all forward rate for a reversible reaction is given by Eq. 2-18. 

 This equation is valid whatever the number of complexes involved in the 

 reaction, i.e., whether one assumes a single active complex ES, or one 

 for both substrate ES and product EP as in reaction 2-17, or more as 

 ES, EXi, EX2...EP. However, the constants F,„, Vp, K,„, and Kp will 

 be represented by different combinations of the rate constants. Equation 

 2-18 may be rewritten as: 



^ (S) - (P) {VJ{JV,„K,) 



"" '- (S) + K,{1 + (?)IK,] ^^'""^ 



