334 CELL HEREDITY 



the differential rate of enzyme formation resulting from the use of low 

 inducer concentrations, and the results in Figure 11.14 bear this out. 



Now let us return to the question of repression in the /3-galactosidase 

 system. Glucose has been found to block the induced formation of many 

 enzymes of carbohydrate metabolism, and in some systems, glucose acts 

 by repressing permease formation, and thereby keeping potential in- 

 ducers of internal enzymes out of the cell. The detailed analysis of "the 

 glucose effect is still in progress, but it already seems likely that its 

 action will, in principle, be found comparable with end-product repres- 

 sion in biosynthetic pathways. Another evidence of similarity between 

 these systems is the fact that permeases have been found which deter- 

 mine uptake of amino acids, as well as of organic acids and other carbo- 

 hydrates. The repression of a permease involved in the arginine path- 

 way has been reported. 



In the past, metabolic control has been studied primarily in terms of 

 substrate availability, on the assumption that the enzymes were not 

 limiting. These recent investigations have shown that the control of 

 enzyme formation and, thereby, of enzyme concentration plays a sig- 

 nificant regulatory role. The precise interplay between substrate levels 

 and enzyme levels in the over-all control of metabolism has scarcely been 

 explored as yet. From the point of view of genetic control devices, 

 however, it is becoming clear that genes exert a continuous influence 

 upon cell metabolism, and that they operate via the control of the rates 

 of enzyme formation. Having considered primarily the effects of in- 

 ducers and repressors in wild-type cells, let us now turn to comparative 

 studies of mutants to get a picture of the role of the genes in this 

 process. 



MUTATIONS AFFECTING RATES OF ENZYME FORMATION 



Mutational effects upon the penicillinase system are summarized in 

 Table 11.2. An inducible strain with a low basal content of penicillinase, 

 which produces high amounts of the enzyme only when induced, has 

 given rise by mutation to so-called "constitutive" mutants which produce 

 much enzyme (25,000 molecules per cell in one instance, 75,000 in an- 

 other) in the absence of penicillin. A noninducible strain, with a basal 

 content of only 15 molecules of penicillinase per cell, has given rise to 

 other noninducible strains producing high titers of the enzyme all the 

 time. Thus it appears that inducibility per se, as well as basal enzyme 

 level is under genetic control. 



In the j8-galactosidase system, a number of classes of mutants have 



