300 Arthur B. Pardee 



the valine pathway by vahne (Adelberg and Umbarger, 1953). 

 More recently, arginine has been found to repress formation 

 of two enzymes in its pathway of synthesis : acetyl ornithinase 

 (Vogel, 1957) and ornithine transcarbamylase (Gorini and 

 Maas, 1957). In the latter work, use of the chemostat for 

 continuous culture at low repressor concentration points the 

 way to a most useful technique for the study of repression. 

 An enzyme of purine biosynthesis is repressible (Magasanik, 

 1957). Also, uracil was found to inhibit the formation of the 

 first three enzymes of the pathway of pyrimidine synthesis; 

 activity of the first enzyme, aspartate carbamyl transferase, 

 was increased 500 times by release of the repression (Yates 

 and Pardee, 1957). The action was shown to be a repression 

 rather than an inhibition by a feedback mechanism of 

 formation of inducers (which w^ould have the same final effect). 

 Also it was shown that repression controlled the synthesis of 

 the enzyme from amino acids, rather than that it took part in 

 some sort of activation phenomenon. This repression of the 

 first specific enzyme of the pathway by an end product six or 

 more steps removed would appear particularly suited for 

 metabolic control. 



It now appears that enzyme induction and enzyme repres- 

 sion are expressions of the same phenomenon. The genetically 

 alternative situation is constitutivity, i.e. the production of 

 an enzyme at a rate independent of the presence of small 

 molecules acting as inducers or repressors. Recent experi- 

 ments indicate that genetically constitutive bacteria lack a 

 repressor for p-galactosidase synthesis. This repressor is 

 synthesized in inducible cells (Pardee, Jacob and Monod, 

 1958); and added inducer serves to overcome the repression. 

 Thus, it would appear that inducible (and repressible) enzymes 

 might be formed in amounts which depend on a balance 

 between inducers and repressors. 



Metabolic regulation 



The experimental observations described above will now 

 be used to suggest a mechanistic scheme for control of bacterial 



