ENZYME INHIBITION AND FEEDBACK CONTROL 



71 



action I, Fig. 3-2) is the conversion of L-threonine to a-ketobutyrate." 

 It had been observed in isotope competition experiments with E. coli 

 that the carbons of exogenous threonine were converted to isoleu- 

 cine (Abelson, 1954). Thus, auxotrophs blocked before threonine 

 use this amino acid not only for incorporation into protein but also 

 for the formation of isoleucine. The requirement for the latter func- 

 tion could be bypassed, however, by incorporating isoleucine into 

 the medium. When this was done, it was noted that isoleucine ex- 



Fig. 3-2. The early steps in the biosynthetic pathways leading to isoleucine 

 and valine. 



erted a sparing effect on the threonine requirement (Umbarger, 

 1955 ) . Thus, the presence of isoleucine somehow prevented threo- 

 nine from being irreversibly converted to any intermediates along 

 tlie pathwav to isoleucine. While the inhibition of any step in the 

 isoleucine pathway would have explained the absence of endoge- 

 nously synthesized isoleucine, only the inhibition of L-threonine 

 deamination, which is irreversible, would have explained the sparing 

 action. While the inhibitor of L-threonine deamination might be any 

 compound freely in equilibrium with the internal pool of isoleucine, 



- So far as is now known, a-ketobutyrate has no other function in the cell than to 

 condense witli a two carbon fragment to yield a-aceto-a-hydroxybutyrate ( Leavitt and 

 Umbarger, 1959). The earHer steps in the pathway between glucose and isoleucine 

 should be considered as the threonine pathway. Therefore, the pathway leading to 

 isoleucine is restricted to those steps of the pathway which lead from the biosynthetic 

 branch point, threonine. 



