S. SPIEGELMAN AND A. M. CAMPBELL 



Secondly, the formation of as little as 0.01 ng of new protein can 

 be detected with ease and precision. 



Precursor and the Nature of the Enzyme-Forming System 



In the present discussion, the term "enzyme-forming sys- 

 tem," hereinafter referred to as EFS, will be used to designate 

 that structure in the cell which is directly and "personally" 

 involved in the process of fabricating the enzyme molecule. 

 This verbal device is employed to isolate the EFS conceptually 

 from all the other cellular components which can and probably 

 do intervene more or less indirectly in the synthetic process. It 

 will, of course, be noted that there is an assumption made here. 

 By so stating the problem we do presume the existence of such a 

 unique structure and, at least implicitly, ignore the possibility 

 that proteins and enzymes are formed by a multitude of cooper- 

 ating and sequential reactions. 



In thinking about the possible nature of the EFS and in 

 designing experiments to clarify the mechanism of its functioning, 

 it is difficult to avoid being influenced by the results of the 

 investigations into the precursor question. In a sense, these 

 findings force an active search for EFS. The data we have 

 reviewed relevant to the precursor problem are satisfyingly clear- 

 cut, almost distressingly so. They lead compellingly to the 

 conclusion that in fabricating a new enzyme molecule, the cell 

 prefers to weave it rather than to stamp it into existence. In 

 this process, the simplest components are employed. Further, 

 we find no evidence for any stable intermediates smaller than 

 that requiring the presence and utilization of all the amino acids. 

 A stepwise formation beginning with simple peptides and pro- 

 ceeding through polypeptides of intermediate lengths would 

 appear to be eliminated. From one point of view, this is of 

 course a pessimistic conclusion. It suggests that a successive 

 approximation to an understanding of how proteins are syn- 

 thesized will not be achieved in terms of a gradually better in- 

 sight gleaned from the study of intermediate pieces of increasing 

 complexity as they approach the final stage of synthesis. A 



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