368 7. INHIBITION IN MULTIENZYME SYSTEMS 



If I '^ ' P is stable, the presence of I will drain off a fraction of the high 

 energy phosphate and the formation of ATP will be decreased. If I '^' P 

 is unstable and breaks down rapidly to I and P, a very small amount of I 

 may be sufficient to uncouple because it will be constantly regenerated. 

 Such cycles or regenerative systems are not limited to phosphate transfer; 

 in any cycle a substance may compete with or combine with an interme- 

 diate so that inhibition may be observed with respect to some product, 

 although the initial substrate would be utilized more rapidly. 



SELF-REGULATORY OR FEEDBACK SYSTEMS 



When one of the intermediates or products of a reaction sequence affects 

 the activity of an enzyme catalyzing one of the previous steps, a self-regu- 

 latory action on the rate may be exerted and such may be termed "feedback 

 systems." Feedback may be positive, if the effect on the enzyme is acti- 

 vation, or negative, if it is inhibition. It is quite possible that this is an 

 important mechanism in the regulation of cellular metabolism, particularly 

 synthetic pathways, although as yet only a few feedback systems have been 

 demonstrated. The action on the enzyme may be either direct or upon its 

 synthesis, as is illustrated in Fig. 7-34. Some examples of direct negative 



Fig. 7-34. Feedback mechanisms. A substrate, S, is taken into the cell and meta- 

 bolized progressively through the intermediates, Xi and Xj, to a product P. This 

 product is able to affect the activity of Eg either directly (lower dashed arrow) 

 or by altering the rate of its synthesis (upper dashed arrow) from amino acids in 

 the enzyme-forming system (EFS). If the product is added to the medium outside 

 the cell, Po, it may enter and exert the same action as the endogenously formed 

 product. (Adapted from Umbarger and Brown, 1958.) 



feedback may be cited: the inhibition of L-threonine deaminase in 

 Escherichia coli, by the product L-isoleucine, preventing the accumulation 

 of its own precursor, since this enzyme catalyzes the initial step in the 

 formation of L-isoleucine from L-threonine (Umbarger and Brown, 1958); 



