84 



MOLECULES, VIRUSES, AND BACTERL^ 



change of conditions, or if the intracelkilar concentrations of metabo- 

 Htes were to vary considerably during a bacterial division cycle. In such 

 cases, the enzyme formed at one time might not be required to func- 

 tion at the same rate shortly thereafter. In brief, induction-repression, 

 which should usually suffice to regulate large-molecule synthesis, could 

 only approximately adjust the synthesis of small molecules to the needs 

 of the cell. 



Another independent means of metabolic regulation has been 

 found. This is known as feedback inhibition (Umbarger, 1956; Yates 

 and Pardee, 1956). It is an inhibition of enzyme function by end prod- 

 ucts of metabolism rather than of enzyme formation. For example, in 

 the presence of a surplus of compound D ( Figure 3 ) , the conversion of 

 A to B can be feedback-inhibited, while at the same time the formation 

 of Ea from amino acids can be repressed. 



Feedback inhibition and repression can both function to regulate 

 the rate of a single metabolic step. This situation has been discovered in 

 several instances; however the functional relation between the two 

 processes has been little studied. 



A unique investigation of the interaction of feedback and repres- 

 sion has been presented in the case of the arginine biosynthetic path- 

 way (Gorini, 1958). The degree of repression of ornithine transcar- 

 bamylase was used to estimate the intracellular concentration of ar- 

 ginine. Various extracellular concentrations of arginine provided in the 

 chemostat were employed. The intracellular arginine concentration 

 ( equivalent to the degree of repression ) must have been constant and 

 low as long as extracellular arginine was provided more slowly than 

 total arginine could be incorporated into cell proteins (Figure 4). At 

 the point where arginine was provided more rapidly than it was bound 

 into protein, the intracellular arginine concentration rose sharply, to 



Amino acids 



X. 



Pq' Eq 



Xg, etc. 



D 



Nutrients 



■^ A 



■^ B 



■^ C 



■^ D 



■^" 



Ec' 

 V Ef 



Figure 3. Schematic representation of a metabolic pathway. Po is a permease; A to F 

 are metabolites; Eo, £.i, to Ey are enzymes; and X.4, Xg, etc., are the "systems" for syn- 

 thesis of £x, Eb, etc. 



