82 CONTROL MECHANISMS IN CELLULAR PROCESSES 



There are now two examples of the phenomenon where the same 

 chemical reaction has two distinctly different physiologicalal roles, 

 and in which the cell has a separate enzyme to perform each func- 

 tion. In each case the enzyme is controlled by factors that make it 

 imiqiiely suited to its particular function. The experience with these 

 systems leads to the proposal of a second principle to come from 

 these studies. This is that whenever a chemical reaction in a cell 

 is catalyzed by an enzyme whose formation and activity are under 

 the rigid control of repression and end-product inhibition, a second 

 enzyme will be needed by the cell if there is some other essential 

 role for that reaction to play in the cell. 



There are additional ways in which an effective feedback control 

 may complicate the metal^olism of a cell. One of these is illustrated 

 again in valine and isoleucine biosynthesis. It was noted earlier 

 that the formation of acetolactate and probablv more specifically 

 the generation of the acetal group required for acetolactate forma- 

 tion is under feedback control by valine. It was also noted that the 

 same enzyme system appeared to catalyze the formation of the cor- 

 responding isoleucine precursor, acetohvdroxybutyrate. The ques- 

 tion then arises: How can isoleucine biosynthesis occur when exoge- 

 nous valine is present? The answer is that, in a cell in which the 

 feedback control by valine is quite effective, it cannot. An example 

 of such an organism is tlie K-12 strain of E. coli, observed long ago 

 to be inhibited by exogenous valine unless isoleucine was present 

 ( Bonner, 1946 ) . It was later shown that any precursor of isoleucine 

 from acetohydroxybutyrate on was able to reverse valine inhibition 

 non-competitively (Umbarger, 1958). Recent experiments would 

 bear out the inference that in the valine-sensitive K-12 strain, there 

 is an extremely effective feedback control so that exogenous valine, 

 in quenching liiosynthesis along its own pathway, also prevents 

 isoleucine formation. In contrast, E. coli strain W, which is not 

 inhibited by exogenous valine, had an acetolactate-acetohydroxy- 

 butyrate-forming system that was less sensitive to inhibition by 

 valine. Likewise, a mutant of the K-12 strain, K-12/V, selected for 

 growth in the presence of valine, exhibited an enzyme less sensitive 

 to inhibition by valine. These differences in the sensitivity to feed- 

 back control were reflected in the level of the free, endogenously 

 formed valine as shown in Table 3-7. In this experiment the cells 

 were harvested at intervals, and the extracellular valine and that 

 liberated from the cells by boiling water were determined. It can 



