80 MOLECULES, VIRUSES, AND BACTERLV 



that they, Hke occasionally used enzymes, be inducible, and some of 

 them are. 



Sequential induction (Stanier, 1951) permits the extension of the 

 ideas of induction to enzymes that are required for the metabolism of 

 biosynthetic intermediates as well as those that act on externally sup- 

 plied nvitrients. In sequential induction the added compound A induces 

 an enzyme, Eg, which converts A to B. Then B induces E^, and the 

 product of this enzyme induces E^, and so on. Chains of up to a dozen 

 enzymes can be induced in this fashion. From our point of interest, it is 

 apparent that enzyme levels can be regulated by induction even though 

 the inducer is not supplied as a nutrient. These findings on sequential 

 induction suggested some time ago that biosynthetic enzymes could be 

 regulated in amount by induction, with biosynthetic intermediates as 

 inducers ( Pollock, 1953; Cohn and Monod, 1953 ) . 



Repression of enzyme synthesis 



Induced formation of a biosynthetic enzyme seemed to be directly 

 demonstrated when an "arginine-requiring" mutant of E. coli was found 

 to produce considerably more acetylornithinase ( an enzyme of arginine 

 synthesis) when the bacteria were grown on acetylornithine rather 

 than on arginine (Vogel and Davis, 1952). However, this was later 

 discovered to be due to prevention of formation of the enzyme by 

 arginine rather than to a stimulation by acetylornithine ( Vogel, 1957 ) . 

 The name "repression" was given to this phenomenon. Several other 

 examples of inhibition of enzyme synthesis by metabolic end products 

 had been noted some years ago. These included repression of trypto- 

 phan synthetase by tryptophan (Cohn and Monod, 1953), of methio- 

 nine synthesis from homoserine by methionine (Cohn and Monod, 1953; 

 Wijesundera and Woods, 1953), of constitutive /3-galactosidase forma- 

 tion by lactose (Cohn and Monod, 1953), and of valine synthesis by 

 valine (Adelberg and Umbarger, 1953). In each case, production of 

 the enzyme was found to be blocked by the end product of the reac- 

 tion or reaction pathway. 



The increase in repressible enzyme requires the synthesis of new 

 enzyme protein. This is shown by studies with aspartate transcarbamyl- 

 ase involving incorporation of an amino acid labeled with carbon 14 

 into the enzyme and by the inhibition of enzyme formation by anti- 

 metabolites or by conditions that blocked protein synthesis ( Yates and 

 Pardee, 1957). 



Recently several instances of repression have been described in 

 somewhat more detail. In these cases, as with the acetylornithinase re- 

 pression, the repressor was a compound at the end of the metabolic 

 pathway, rather than the direct product of the enzyme reaction itself. 



