CONTROL BY REPRESSION 53 



is thought to have affinity) could be on the nascent enzyme, on the 

 ribosome, or on both. A repressor site on the nascent enzyme need 

 not be identical with the nascent dynamic (catalytically active) site 

 of the enzyme (Vogel, 1958). 



Repression in the Control of Cellular Function 

 and of Development 



Repression and Feedback Inhibition. Quite different from re- 

 pression is the phenomenon of feedback inhibition, which charac- 

 teristicallv consists in the interference with the flow of metabolites 

 through a pathway by inhibition of an early enzymatic step of the 

 pathwav, through the agency of the "end product" involved. Feed- 

 back inhibition thus occurs at the level of enzvme action rather than 

 of enzyme formation and can be viewed as a control mechanism 

 that frequentlv, but not necessarilv, acts in parallel with repression 

 of enzyme formation. Since feedback inhibition is the subject of 

 Dr. Umbarger's detailed, basic contribution to this volume (Chap. 

 3 ) , only certain instances of such inhibition that bear rather directly 

 on enzyme repression will be considered here. 



Gorini (1958) has carried out a study of arginine repression of 

 ornithine transcarbamvlase in relation to feedback inhibition in the 

 arginine pathway of a strain of E. coli. In experiments with the 

 chemostat, at a given bacterial density, added arginine does not be- 

 come repressive for the transcarbamylase, until the supply of this 

 exogenous amino acid exceeds that necessary for an arginine-re- 

 quiring mutant of this strain to attain the same density. Maximal 

 feedback inhibition appears to take place at intracellular arginine 

 concentrations lower than those needed to give maximal repression. 

 These two mechanisms thus tend to cooperate in furnishing an eco- 

 nomical and efficient control system which, within appropriate limits, 

 permits an ( endogenous ) synthesis of arginine that is precisely com- 

 plementary to the supply of ( preferentially utilized ) exogenous argi- 

 nine. 



Witli the aid of metabolite analogues, it has been shown that 

 certain compounds (false feedback inhibitors) can mimic, under 

 suitable conditions, the end product of a pathway in its action as a 

 feedback inhibitor but not as a repressor. For instance, the anti- 

 metabolite 2-thiazolealanine was found to give such false feedback 

 inliibition of histidine synthesis in E. coli (Moyed, 1960; Sliedlovsky 



