388 B. Magasanik, et al, 



required for the oxidation of pyruvate and ketoglutarate. 

 The result of these effects is the accumulation of pyruvate 

 and ketoglutarate, which are the precursors of most of the 

 amino acids, and of gluconate or its phosphate, which is an 

 important precursor of ribose and deoxyribose. Presumably, 

 the high level of these essential metabolites is responsible for 

 the rapid growth of the cells on glucose, and for the repression 

 of the glucose-sensitive enzymes whose action would augment 

 the already large pools of these metabolites. 



It may, therefore, be concluded that enzyme repression is a 

 general phenomenon and is not restricted to one particular 

 class of enzymes. 



The question now arises, by what mechanism the repressor, 

 a small molecule, can prevent the synthesis of a specific 

 protein. We have shown previously that glucose, or rather an 

 intracellular product of its metabolism, exerts its effect on 

 enzyme synthesis by interfering with the action of the enzyme- 

 forming system, and not by preventing its formation, or by 

 causing its destruction (Neidhardt and Magasanik, 1956Z)). 

 These results would be in accordance with the hypothesis that 

 enzyme biosynthesis is regulated by the interaction of the 

 enzyme -forming system with repressors and inducers (Vogel, 

 19576; Szilard, 1958, personal communication). According to 

 this hypothesis [which in the case of p-galactosidase is sup- 

 ported by the brilliant experiments of Pardee, Jacob and 

 Monod (1958)], the primary control of enzyme formation is 

 exerted by the repressor, which may be thought to bind a 

 newly formed enzyme molecule to the enzyme-forming 

 machinery, and thus to prevent the further synthesis of 

 enzyme molecules; the inducer would stimulate enzyme pro- 

 duction by preventing the interaction of the repressor with 

 the complex of enzyme and enzyme-forming system. 



In the light of this hypothesis, repressors and inducers do 

 not influence the formation of the enzyme -forming system, but 

 control its action. 



A large body of indirect evidence points to ribonucleic acid 

 (RNA) as the enzyme-forming system (Brachet, 1955). It 



