THE ROLE OF ENZYME REGULATION IN METABOLISM 79 



sort suggest that the amounts of some enzymes are determined by the 

 concentrations of their substrates, those enzymes being made in largest 

 amounts whose substrates are most plentiful. A consequence of induc- 

 tion is that if a substrate were to stimulate enzyme formation suffi- 

 ciently, the enzyme would reduce the substrate level inside the cell to 

 a value too low to induce further enzyme synthesis; thus the level of 

 that enzyme could not increase indefinitely but would be determined 

 by the rate at ^^'hich its substrate became available. Eventually a steady 

 state would be reached in which supply and removal were balanced. 

 Induction could thus provide a means of regulating synthesis of en- 

 zymes so as to provide ample ( but not excess ) enzyme, as measured by 

 the availability of its substrate. 



Known inducible enz)'mes are almost invariably catalysts of proc- 

 esses by which energy is obtained from externally supplied nutrients. 

 Two limitations of induction as a means of regulating such processes 

 are apparent. First, there is no obvious way of limiting enzyme produc- 

 tion to a level which just meets the requirements of the cell for the 

 products of the enzyme action. Indeed, inducible enzymes can be pro- 

 duced under "gratuitous conditions" (Monod and Cohn, 1952) in 

 which the cell does not require them at all. Second, induction per se 

 allows the formation of the enzyme even when an alternative, more 

 readily used, source of energy is available. In certain instances of this 

 sort, however, the well-known phenomenon of diauxie ( Monod and 

 Cohn, 1952) does limit the induction of catabolic enzymes. For ex- 

 ample, when glucose is added to a culture producing tryptophanase, 

 enzyme formation ceases abruptly (Figure 1), and therefore trypto- 

 phan is no longer used as a source of energy. In spite of much effort, 

 the mechanism of diauxie is not understood. Perhaps the most reason- 

 able explanation is that the bacteria can form a variety of low- 

 molecular-weight compounds from glucose, each of which specifically 

 prevents production of enzymes involved in the synthesis of that com- 

 pound ( Magasanik, 1957 ) . This concept is based on enzyme repression, 

 which will be discussed later. 



The subject of induction cannot be presented without mentioning 

 the enzyme-like factors ( named permeases ) that permit the entry and 

 concentration of metabolites within cells (Cohen and Monod, 1957). 

 These must play a role in metabolic regulation. Entry of a nutrient into 

 the cell is generally the first step in its metabolism. Permeases make 

 available at high intracellular concentrations nutrients present at low 

 concentrations in the environment and thereby permit the nutrients 

 to be metabolized rapidly by a hmited amount of enzyme. Permeases, 

 therefore, play a role in the economy of the cell by diminishing the 

 requirements for enzymes. However, to avoid expenditure of energy in 

 the formation of the permeases themselves, it would seem beneficial 



