302 Arthur B. Pardee 



reactions are not necessary if the rates must be equal to the 

 rates of the preceding reactions (i.e. wherever their enzymes 

 are present in adequate amounts, perhaps provided through 

 induction mechanisms). Certain steps of the pathway 

 ("pacemaker reactions") must somehow be controlled. First, 

 the end product of a series of reactions must somehow be 

 limited so as to co-ordinate with products of other pathways. 

 Second, if two pathways diverge from some compound (as 

 from C in Fig. 1), some regulation of the partition of the com- 

 pound between these sequences is required [alternative 

 metabolic pathways (Potter and Heidelberger, 1950)]. Feed- 

 back inhibition at the first specific step of a sequence could 

 provide an adequate means of control, since the rate of the 

 entire pathway would depend on the accumulated end 

 product. Examples of the validity of this idea are found in 

 the observation that an amino acid provided in the medium 

 usually prevents its own synthesis by Esch. coli: the amino 

 acids formed de novo (from a radioactive carbon source) are 

 found neither in the bacterial proteins nor in the medium nor 

 inside the cells under these conditions (Roberts et al., 1955). 



Enzyme repression could also function to limit pacemaker 

 reactions. In one case repression might act, and in another 

 feedback inhibition could serve. The time required for these 

 actions to be effective must be quite different, however. 

 Whereas inhibition should act instantaneously, repression 

 must have a more gradual action. Although the latter com- 

 mences immediately, some time would be required to increase 

 the enzyme concentration and especially to decrease an exist- 

 ing concentration of enzyme (by growth without enzyme 

 synthesis). 



(c) Formation of end prodiccts. Large molecules (such as 

 enzymes) should not be synthesized in excess of the quantities 

 that are required for growth, for efficient functioning of 

 bacteria (since the formation of a large molecule must require 

 energy). Thus, for example, a bacterium could have a selective 

 advantage if it did not have to make p-galactosidase when no 

 galactosides were available. Repression and induction thus 



