148 S. S. COHEN 



nor enzyme is made. If the permease is preinduced and glucose is added in 

 the presence of low amomits of inducer, enzyme formation is not affected for 

 many generations, since premduced bacteria will be able to maintain a high 

 inducer concentration and will make permease and galactosidase at a high 

 rate despite the presence of inhibitory glucose. The permease systems once 

 formed thus tend to perpetuate themselves under suitable conditions. Pardee 

 (1957) has recently shown that the formation of the galactoside-permease but 

 not of /3-galactosidase can be induced by certain a-galactosides in E. coli 

 strain B, but not in strain ML. Stoeber (1957) has recently described a 

 /S-glucuronide-permease distinct from the galactoside system. 



G. N. Cohen and Rickenberg (1956) have shown the existence of a series of 

 specific systems (presumably permeases) for the reversible concentration of 

 exogenous amino acids, prior to incorporation into proteins (see also Britten 

 et at., 1955). It is thought that each amino acid may have its specific per- 

 mease. A number of interactions of amino acids inhibitory to growth may be 

 explained by their effects on these systems. As with other permease systems, 

 the oxidation of glucose inhibits penetration of amnio acids into bacteria 

 (Gale, 1947; Mandelstam, 1956a). The latter worker has also shown that the 

 penetration of basic amino acids is competitively inhibited by the correspond- 

 ing diamines (Mandelstam, 1956a,b). A review of bacterial permeases has 

 recently appeared (Cohen, G. N., and Monod, 1957). 



6. On the Inhibition of Enzyme Formation 



As we have seen, inducers need not be substrates, but most often a substrate 

 of an inducible enzyme is structurally very similar to an inducer. In addition, 

 in a given sequence of reactions, a precursor or a reaction product will also 

 resemble the substrate structurally and the latter, particularly, may even 

 act as an inliibitor of induction. As an mstance in which a precursor is 

 inhibitory m a reaction sequence may be mentioned the conversion of 



dehydroshikimic acid > shikimic acid > phosphoshikimic 



acid > aromatic amino acids. In this system the accumulation 



of dehydroshikimic acid inhibits the subsequent metabohsm of shikimic 

 acid. 



Many cases are known m which reaction products inhibit enzyme forma- 

 tion. This phenomenon is most readily demonstrated for constitutive sys- 

 tems. Thus, the synthesis of tryptophan desmolase in Aerobacter aerogenes is 

 stro2igly inhibited by both tryptophan and by indole (Monod and Cohen- 

 Bazire, 1953) and the synthesis of methionine synthetase in E. coli is in- 

 hibited by the presence of methionine (Cohn et al., 1953a). Such effects take 

 on the aspect of negative feed-back systems and have the general consequence 

 of preventing a cell from forming an enzyme when it is not needed. 



