150 S. S. COHEN 



Most recently it has been shown that the synthesis of ornithine trans- 

 carbamylase is also inhibited by arginine in a mutant blocked in the conver- 

 sion of acetylornithine to ornithine. If such a mutant is grown under 

 conditions in which arginine is immediately assimilated into protein, i.e., in 

 a chemostat in which the supply of arginine is carefuUy regulated, the amount 

 of the transcarbamylase formed attains a level 25 times that of the steady 

 state concentration in the wild type bacterium. Thus, wild type cells have 

 a markedly greater potential than is permitted to operate for the synthesis 

 of enzymes controlling the production of essential constituents; these poten- 

 tials are repressed by negative feedback mechanisms. In the absence of such 

 repression the initial rate of synthesis can be far more rapid than that of cell 

 mass; a constant differential rate of synthesis obtains only when the accumu- 

 lation of product and inhibition of enzyme synthesis establish steady state 

 conditions (Gorini and Maas, 1957). 



7. Inducible Phenomena in Higher Forms 



Knox et al. (1956) have written an extensive summary of enzymatic and 

 metaboHc adaptations in animals. In many instances recorded by these 

 authors the metaboKc change resulting from some environmental effect may 

 weU represent phenomena of mduced biosyntheses of enzymes. Thus, one of 

 the earhest examples is the formation of ^-galactosidase in the pancreas of 

 dogs after ingestion of lactose. On the other hand, the abihty of rats to handle 

 galactose is not affected by galactose intake, and this ability is maintained 

 desjiite a prolonged absence of galactose from the diet (Feigelson and Conte, 

 1954). 



A most careful demonstration of the induced biosynthesis of an enzyme in 

 the mammal has been that of the increase of liver tryptophan peroxidase in 

 response to the injected try^Dtophan and some other substances, such as 

 adrenahn or histamine (Knox and Mehler, 1951). In rats this phenomenon 

 proved to be due to two independent mechanisms, of which one was specific 

 for tryptophan and resembled the mechanism observed in microorganisms. 

 The other relatively nonspecific increase in the enzyme arose as a result of 

 stimulation of the pituitary-adrenal system and was abohshed by adrenal- 

 ectomy. The latter revealed a hormonal control, not of enzymatic reactivity, 

 but of the amount of an enzyme elaborated (Knox, 1951). In this instance the 

 increase in level of tryptophan peroxidase is attributable to cortisone release 

 from the adrenal (Knox and Auerbach, 1955). 



The instances of metabohc adaptation surveyed by Knox et al. (1956) have 

 not yet been reproduced in isolated cell systems in tissue culture, in which a 

 constant genetic background can be maintained. There is httle doubt but 

 that the major advances in technique in tissue cultures will produce investi- 

 gations of this character. In one study of this tj^e, Lieberman (1957) explored 



