364 



General Discussion 



here identify as involving the control metabolites M and N, re- 

 spectively : 



A 



4^. 



(Fig. IG) 



N 



^N 



^N 



If metabolism along pathway M involves, in addition to the usual 

 control mechanisms, the formation of inhibitors (I) or activators (A) 

 in branched pathways, it is easy to see that the formation of such 

 substances, either from M' or from any other source in the cell, 

 could readily change the balance of metabolism through the M and 

 N pathways. An ideal substance for shifting metabolism from one 

 pathway to another would be one that inhibits pathway M and 

 activates pathway N. It is my purpose, however, to emphasize 

 that any discussion of metabolic control presumes that there exists 

 in the cell a substance whose concentration controls the metabolic 

 pathway of interest. From that point onwards, pathways capable 

 of activating or inhibiting the control system can easily be visualized. 

 Magasanik: We have studied one case where this sort of branching, 

 and its control, can be nicely seen. In certain species of bacteria, for 

 instance Aerobacter aerogenes, and in certain animal tissues, e.g. 

 liver, histidine can serve two functions: it can be incorporated 

 directly into protein, or it can be degraded to glutamic acid, which 

 can be used as a source of energy and of non-specific building blocks. 

 We can see that the cell is therefore faced with the problem of 

 whether to use the histidine for protein synthesis, or to break it 

 down. We found several years ago (Magasanik, B. (1955). J. hiol. 

 Chem., 213, 557), that a histidine-requiring mutant of ^. aerogenes 

 could reach full growth in a medium containing glucose as the major 

 source of carbon and a small supplement of histidine, in fact roughly 



