THE ROLE OF ENZYME REGULATION IN METABOLISM 89 



TABLE II 



Synthesis of Protein and Nucleic Acids 

 by Fully Fed and by Starved Mutants 



Increase in one hour (per cent) 



Growth Requirement Absent Protein RNA DNA 



none ~120 -120 ~120 



uracil +6 -6 -10 



leucine +6 +15 +32 



tryptophan —3 +20 



lated at the point of their connection to produce the macromolecules; 

 i.e., a deficiency in an amino acid would limit protein synthesis, which 

 in turn would diminish nucleic-acid synthesis and thereby reduce the 

 rate of utilization of purines and pyrimidines, which in turn would de- 

 crease the rates of synthesis of the latter. 



Other problems 



As might be expected, and certainly as would be desired, the find- 

 ings to date raise many more problems than they answer. The ques- 

 tions that arise are of varied sorts and relate to methods, systems, ex- 

 ternal influences, and internal mechanisms. Methods for study of these 

 phenomena depend at present mainly on measurement of the amounts 

 of products formed under a variety of conditions brought about by 

 genetic blocks, inhibitors, nutrient additions, and combinations of these. 

 One can, for example, examine overproduction of intermediary or ter- 

 minal metabolites or enzymes in a growing culture, or determine com- 

 petition of small molecules provided as nutrients or formed de novo for 

 incorporation into macromolecules. One can study the maximum rate 

 of production of a metabolite in vitro and compare it with the rate cal- 

 culated from in vivo measurements of end-product formation. Feed- 

 back inhibition already can be studied in vitro, and evidence for en- 

 zyme synthesis in vitro is accumlating rapidly enough to give hope 

 that cell-free systems will permit induction-repression as well to be in- 

 vestigated with isolated parts of the synthetic apparatus of the cell. 



The systems so far studied have been almost entirely those dealing 

 with components produced in large amounts— amino acids and nucleic- 

 acid bases. Are there also similar regulatory processes for synthesis of 

 components made in minute quantities? Production of coenzymes is 

 only about 1/1000 as great as that of amino acids. How efficiently are 

 these compounds formed? Unpublished findings (Wilson, 1960) on the 



