82 MOLECULES, VIRUSES, AND BACTERL\ 



synthesis correlates in\'ersely with the supply of pyrimidines available 

 to the bacteria. 



Another recent, striking instance of enzyme repression is found 

 with alkaline phosphatase of E. coJi. This enzyme, normally present in 

 a minute amount, increases enormously when the concentration of 

 phosphate in the medium is reduced, and under certain conditions can 

 reach several per cent of the cell protein ( Horiuchi et al., 1959; Tor- 

 riani, 1960). 



Inducers are now thought to act by reversing the action of an intra- 

 cellular repressor. This is suggested by experiments on the formation of 

 /3-galactosidase by bacterial zygotes which contain both the active and 

 inactive forms of a gene that controls repressor formation (Pardee et 

 al., 1959). The gene present in inducible bacterial was dominant over 

 that found in constitutive bacteria; therefore the former appears to be 

 the active allele and appears to produce a repressor of enzyme syn- 

 thesis. The competition of inducer and repressor for the control of 

 enzyme formation has been strikingly and directly demonstrated for 

 ornithine transcarbamylase, which is repressed by arginine. Ornithine 

 can reverse arginine's effect (Gorini, 1960). One visualizes an active 

 site which prevents protein synthesis when bound by a repressor but 

 permits enzyme synthesis when combined with an inducer. 



When such a controlling site is not boimd by either inducer or re- 

 pressor, enzyme is formed. Therefore, constitutive formers of the en- 

 zyme are thought to be organisms which cannot make repressor ( Par- 

 dee et al., 1959 ) . Mutants in which the binding site is so modified as 

 not to accept the repressor are also constitutive (Jacob and Monod, 

 1959). In addition to constitutive producers of /?-galactosidase and 

 amylomaltase ( Cohen-Bazire and Jolit, 1953) and penicillinase (Pol- 

 lock, 1959), investigators have recently isolated mutants constitutive 

 for the production of tryptophan-synthesizing enzymes (Cohen and 

 Jacob, 1959), aspartate transcarbamylase (Shepherdson and Pardee, 

 1960 ) , and ornithine transcarbamylase ( Gorini, 1960 ) . 



Evidence has appeared that a set of related enzymes can be re- 

 pressed as a group : four enzymes of histidine synthesis are all repressed 

 in proportion if histidine is present ( Ames and Garry, 1959 ) . The en- 

 zymes are separate proteins; hence the repressor cannot function by 

 blocking synthesis of a complex, multifunctional enzyme particle. Fur- 

 thermore, the genes that guide the synthesis of these enzymes are 

 closely linked, providing the interesting speculation that the binding 

 site of the repressor is on the genetic material. Similarly, a locus on the 

 chromosome adjacent to the set of genes involved in /3-galactoside 

 metabolism is thought from genetic evidence to bind a repressor 

 capable of affecting all of these genes (Jacob et al., 1960). Concepts 



