90 MOLECULES, VffiUSES, AND BACTERL\ 



synthesis of flavins by E. coli show that the rate of flavin synthesis is 

 almost constant, relatively independent of the rate of growth or protein 

 synthesis, under a variety of conditions of inhibition or nutritional sup- 

 plementation. A considerable portion of the flavins, perhaps half, is ex- 

 creted into the medium by the growing cells. Such results suggest that 

 mechanisms of control of flavin production must difi^er, at least quanti- 

 tatively, from those so far found to regulate the synthesis of components 

 present in larger amounts. 



It is worthy of note that almost all data on metabolic regulation in 

 bacteria have been obtained with E. coli. Do similar mechanisms exist 

 in other microorganisms? What of the relatively large pools of amino 

 acids in some organisms— yeasts, for example? To what extent does one 

 find these regulatory processes in higher organisms? 



The influence of external factors other than substrates could well be 

 exerted through repression or feedback mechanisms. Analogs of nat- 

 ural metabolites inhibit growth, but often they are readily overcome by 

 very small amounts of the compounds they resemble. If such an analog 

 was not able to prevent de novo synthesis of the natural compound, 

 the analog could not be toxic, because the endogenous natural product 

 would reverse its eflfect. Therefore it is probable that such analogs func- 

 tion, in part at least, by feedback inhibition of pathways for synthesis 

 of their natural relatives. Examples of this phenomenon are known: in- 

 hibition of tryptophan synthesis by tryptophan analogs ( Trudinger and 

 Cohen, 1954; Pardee and Prestidge, 1958), synthesis of histidine 

 ( Moyed and Friedman, 1960 ) , inhibition of purine synthesis by purine 

 analogs (Gots and Gollub, 1959), and inhibition of pyrimidine syn- 

 thesis by 6-azauracil ( Handschumacher, 1958 ) . 



Finally, one must mention a series of problems hardly touched upon 

 in this article— the question of the mechanism of these effects, especially 

 of induction and repression. Foremost are questions such as the nature 

 of the repressor and the site of binding of the repressor and inducer in 

 the cell. Answers to these problems, of great interest in themselves, 

 should help us understand the ways in which regulatory processes func- 

 tion in the living cell. 



References 



Adelberg, E. A., and Umbarger, H. E., 1953. Isoleucine and Valine Metabolism in 



E. coli, V: a-Ketoisovaleric Acid Accumulation," /. Biol. Chem. 205, 475. 

 Ames, B. N., and Garry, B., 1959. "Coordinate Repression of the Synthesis of Four 



Histidine Enzymes by Histidine," Proc. Natl. Acad. Sci. 45, 1453. 

 Brooke, M. S., Ushiba, D., and Magasanik, B., 1954. "Some Factors Affecting the 



Excretion of Orotic Acid by Mutants of Aerobacter aerogcncs," J. Bad. 68, 



534. 

 Cohen, C, and Jacob F., 1959. "Sur la repression de la synthese des enzymes in- 



