296 Arthur B. Pardee 



found inside them, perhaps 10 per cent of the amount incor- 

 porated (Roberts et al., 1955). Therefore, on the average the 

 reactions are controlled to run within about 10 per cent of the 

 minimum necessary rate. One naturally asks how such a 

 controlled system operates. 



The aim of the present paper is to discuss the extent to 

 which recent discoveries permit a description of the inte- 

 gration of metabolic processes. Bacterial metabolism is not 

 rigidly fixed but is made up in a very flexible way, so that as 

 conditions are changed the reactions adjust and attain a new 

 balance with their surroundings in order to permit growth. 

 Therefore, one must seek mechanisms which accelerate the 

 rates of individual reactions when their reaction products are 

 not made as rapidly as other metabolites, and other (or 

 similar) mechanisms which lower the supply of these products 

 when they are in excess over the demands of overall growth. 

 For the greatest possible economy of the cell it would be 

 desirable to prevent the formation of surpluses of two sorts of 

 products, (i) metabolic intermediates and (ii) large molecules, 

 such as enzymes. One might hope to find mechanisms which 

 prevent formation of surpluses of each of these kinds of 

 products of cell metabolism. Several such mechanisms have 

 indeed been described recently, and some examples will be 

 noted below. In conclusion, some comments will be made 

 regarding the manner in which these mechanisms may func- 

 tion. The subject has recently been discussed extensively 

 (LwofP, 1957; Magasanik, 1957; Pardee, 1958). 



Types of regulation 



Metabolic requirements can be expressed in terms of changes 

 in the concentrations of certain small molecules inside the 

 cells ; these, in turn, might regulate the rates of key reactions 

 in the metabolic pathways. Small molecules may have two 

 general kinds of effect on enzymes : they can alter the rate of 

 synthesis of an enzyme, or they can modify the rate at which 

 an enzyme molecule functions. In both cases the effect of the 

 small molecule can either be positive or negative. One of 



