ENZYME INHIBITION AND FEEDBACK CONTROL 83 



be seen that the K-12 strain witli its \er\ sensitive acetolaetate- 

 forming system, had a very small internal pool of valine. On the 

 other liand, in those strains (W and K-12/V) in which acetolactate 

 formation was more resistant to inhibition by valine, the intracellular 

 pool of free valine was high. Toward the end of growth, when 

 aeration became the limiting factor, valine as well as other amino 

 acids were excreted. Until this excretion occurred, the external 

 valine was almost undetectable. Thus, because of the unique fea- 

 ture in isoleucine and valine biosvnthesis of a series of common 

 enzymes for the two pathways, the cell can have either good feed- 

 back control over valine biosynthesis or an isoleucine pathway re- 

 sistant to valine, but not both. 



TABLE 3-7 

 The Regulation of Free Intracellular Valine by Its Feedback Control 



Free Intracellular Pool 

 Inhibition of Mg Valine/mg Cell Protein 



Acetolactate Formation 



Strain by Valine O.D. = 200 O.D. = 400 



K-12 Strong 0.4 0.2 



K-12/V WeAk 3.8 2.0 



W Weak 2.7 1.4 



A closely related complication arising in a feedback mechanism 

 has been described by Moyed and Friedman (1959b). In this ex- 

 ample, an analog of the end product may so resemble the natural 

 product that, although it cannot be incorporated into a macromole- 

 cule, it may prevent growth by inhibiting the enzyme that is nor- 

 mallv subject to end-product inhibition, i.e., by exerting "false 

 feedback." The antagonism by the end product of the action of 

 such an inhibitor would be expected to be non-competitive. How- 

 ever, Moyed and Friedman (1959a) described an example in which 

 tliis did not occur. 5-Methyltryptophan, a weak inhibitor of an early 

 step in tryptophan biosynthesis, also hinders the entry of tryptophan 

 so that a precursor of trvptophan, indole, is more effective in revers- 

 ing the action of the analog than is tryptophan itself. 



The experiments of Moyed have, in addition, demonstrated that 

 one way for a cell to become resistant to an analog which exerted 

 "false feedback ' was for the sensitive enzyme to become resistant 

 to the action of the analog. Examination showed that one such 



