ENZYME INHIBITION AND FEEDBACK CONTROL 73 



of isoleucine in the wild-type organism is prevented and, in tlie 

 presence of a mechanism for the entry of isoleucine into the cell, 

 accounts for the sparing effect on the threonine requirement of thre- 

 onine auxotrophs, for the failure of isoleucine auxotrophs to accu- 

 mulate precursor until the growth factor is exhausted, and for the 

 preferential utilization of exogenous isoleucine. 



As is emphasized elsewhere in this volume, end-product inliibi- 

 tion of the initial enzyme in a biosynthetic sequence is not the only 

 mechanism for controlling biosynthesis. Indeed, while studying the 

 accumulation of isoleucine precursors, it became clear that isoleucine 

 not only exerted an inhibitory effect on the action of threonine de- 

 aminase but also on the formation of the enzyme (Umbarger and 

 Brown, 1958a). However, in the strains examined, the inhibitory 

 effect on the formation of threonine deaminase (enzyme repres- 

 sion ") was not complete, i.e., a basal level of L-threonine deaminase 

 was assured even in the presence of excess isoleucine. This incom- 

 plete repression is in marked contrast to the findings in the arginine 

 synthesizing enzymes of certain strains of E. coli (Vogel, 1961). 



Thus, in the isoleucine pathway two kinds of control operate. In 

 order that the patterns of the two may be clearly differentiated, their 

 essential features are shown diagrammaticallv in Fig. 3-3. In this 

 scheme the end product of the biosvnthetic sequence, P, whether 

 formed endogenously or having entered from outside the cell, takes 

 part in a feedback loop ( // ) . When its concentration is sufficiently 

 high, P blocks the action of the first enzyme (a) in the sequence 

 which converts A, an intermediate supplied by glucose catabolism, 

 to P. This is the pattern revealed so strikingly in the isoleucine 



3 The temi "repression" was introduced as an operational term in the phrase "repres- 

 sion of enzyme formation" by an end product (Vogel, 1956). It has been quite con- 

 venient, yet sufficiently explicit, to use the single word "repression" in referring to this 

 operational concept. Graduallv, the term has also come to imply the concept of the 

 physiological significance attributed to the repression of enzyme formation as a feed- 

 back mechanism. This has been a very natural evolution and has not required the 

 introduction of new words or the redefinition of old ones. Unfortunately, it has not 

 been possible to derive a similarly specific, operational word for the phrase "inhibition 

 of the activity of the initial enzyme in a biosynthetic sequence," etc. The term "feed- 

 back inhibition" is not an operational term but, rather, one that implies a functional 

 significance. It would be useful, therefore, to employ a term which is operationally 

 explicit and yet implies that the interaction in question is potentially important as a 

 feedback mechanism. While not entirely satisfactory, it is proposed here that tire 

 phrase "end-product inhibition" be employed to describe the inhibition of the activity 

 of the initial enzyme in a biosynthetic sec^uence by the end product of that sequence. 

 Use of that phrase does not re<[uire proof of the physiological importance of the inter- 

 action yet signals its potential importance. 



