CONTROL BY REPRESSION 31 



the four enzvmes appear to derepress jointly and at tlie same rate, 

 within tlie accuracy of the enzyme assays used. Hence, the initial 

 extent of repression is the same for all foui' enzymes, a phenomenon 

 called "coordinate repression" by Ames and Garry (1959). Recent 

 findings indicate that at least two, and probably all, of the earlier 

 enzymes in tliis patliway are repressed coordinately with the last 

 four (Ames, 1960; Magasanik, 1960). These results, in conjunction 

 with those of Hartman et al. (1960a, 1960b), are considered again 

 in the section Genetic Aspects. Coordination does not, however, 

 seem to be a necessary attribute of the repression of enzymes within 

 a giyen biosynthetic sequence, since, as pointed out by Ames and 

 Garr\- ( 1959 ) , the repression of three enzymes of pyrimidine biosyn- 

 thesis (Yates and Pardee, 1957) apparently is non-coordinate. 



Repression as a Function of Intracellular Repressor Con- 

 centration. As discussed aboye, release from repression is obtained 

 when the supply of the appropriate repressor available to the cell 

 is restrictive. A dependence of repression or derepression on the 

 intracellular repressor concentration is thus indicated. In the case 

 of acetylornithinase, restrictive supply conditions of the repressor, 

 arginine, were realized during rate-limiting growth of an arginine- 

 requiring mutant on acetvlornithine (Vogel, 1953a, 1957a. 1960a). 

 Slowly utilizable substrates likewise proved useful in derepression 

 studies of enzymes of pyrimidine ( Yates and Pardee, 1957; Sheperd- 

 son and Pardee, 1960b) and histidine (Ames and Garry, 1959) syn- 

 thesis. A restrictive supply of repressor can also be achieved in a 

 number of other ways: with leaky mutants (Yates and Pardee, 1957; 

 Maas and Novick, 1958; Ames and Garry, 1959; Yanofsky, 1960; 

 Shepherdson and Pardee, 1960b); with mutants growing in a chemo- 

 stat on a limited amount of repressor (Gorini and Maas, 1957, 1958) ; 

 with cells, e.g., protoplasts or mutants, having impaired concentrat- 

 ing mechanisms (Rogers and Novelli, 1959; Schwartz et ah, 1959; 

 Maas, 1959); by interference with the synthesis of an endogenous 

 repressor through the use of an antimetabolite (Lester and Yanofsky, 

 I960; Mo\'ed, 1960) or of constraining metabolic conditions, e.g., 

 anaerobiosis ( Gorini and Maas, 1958 ) ; or by selective enrichment of 

 repressor-free culture medium ( Gorini and Maas, 1958 ) . 



In the derepression experiments with acetylornithinase and the 

 enzymes of histidine synthesis ( Fig. 2-1 and 2-3 ) , derepressive con- 

 ditions were maintained following the onset of derepression. The 



