ENZYME INHIBITION AND FEEDBACK CONTROL 



69 



factor exhaustion. If growth stopped for some otiier reason wliile 

 growth factor was still present, there was no precursor accumula- 

 tion. It was therefore concluded that the addition to the medium 

 of the end product of a biosNuthetic sequence prevents further syn- 

 thesis not onh of that end product, as had been revealed bv the 

 isotope competition experiments, but also of very early intermediates 

 as revealed by the stud\ of precursor accumulations. 



GROWTH FACTOR 



TIME 



Fig. 3-1. Relationship of the accumulation of a precursor by an auxotrophic 

 mutant to its growth. 



A kinetic experiment like that represented in Fig. 3-1 does not 

 permit one to decide which of two possible mechanisms is respon- 

 sible for delayed accumulation The failure of the precursor to ac- 

 cumulate until the end product has disappeared could be due either 

 to the absence of one or more enzvmes in the pathway or to the 

 failure of at least one enzyme to function. Actually by the time this 

 inhibition of endogenous synthesis by the end product had been 

 recognized as a general property of biosynthetic pathwavs in micro- 

 organisms, there was already evidence which supported both pos- 

 sibilities. 



In support of the idea that one or more enzymes in the pathway 

 might be absent as long as exogenous end product was present, there 

 were the observations by Cohn et al. ( 1953 ) and independently by 



