THE ROLE OF ENZYME REGULATION IN METABOLISM 



85 



3 

 O 



> 



< 



(T 







Arginine needed for growth 



■"^y^Vceii 



Rote 

 Arginine Synthesis 



4 6 8 



ARGININE SUPPLIED, /xg/ml 



Figure 4. Feedback and repression in the arginine pathway (after Gorini, 

 1958). 



cause a much stronger repression. One can conclude that feedback in- 

 hibition regulates the intracellular arginine concentration and limits the 

 de novo synthesis of arginine to just the rate necessary to make up the 

 difiPerence between externally added arginine and the amount required 

 for protein synthesis. Repression takes effect strongly only when ar- 

 ginine is available in excess of growth requirements. Repression is 

 therefore a secondary control in this instance. 



A number of earlier observations strongly indicated that feedback 

 inhibition mechanisms existed. Among these were chemostat studies on 

 production of an indole-like compound by a tryptophan-requiring E. 

 coli mutant ( Novick and Szilard, 1954 ) . This compound was produced 

 only when the suppK' of tryptophan limited the growth rate of the or- 

 ganism. Since it was almost certainly a by-product created at the 

 metabolic block of the tryptophan pathway, tryptophan must have in- 

 hibited the pathway at some earlier point— actually prior to anthranilic 

 acid ( Pardee and Prestidge, 1958 ) . Data were presented to show that 

 tryptophan, rather than something else connected with the rate of 



