General Discussion 365 



the amount of histidine required according to the histidine content 

 of the bacterial protein. When glucose was replaced by another 

 carbon compound, e.g. glycerol, inositol or pyruvate, about 

 twenty times as much histidine had to be supplied to permit the 

 culture to reach full growth. It was eventually found that glucose 

 prevented the formation of the enzymes required for the conversion 

 of histidine to glutamate, and thus preserved the histidine for its 

 specific function, namely its incorporation into protein. The other 

 carbon compounds were not metabolized as rapidly as glucose, and 

 therefore failed to provide the repressor for the formation of the 

 enzyme system responsible for the degradation of histidine; the 

 conversion of histidine to glutamate, under these circumstances, 

 provided the cell with additional energy and building blocks, but 

 robbed it of histidine, the specific protein precursor. 



In an organism capable of producing and of degrading histidine, 

 the intracellular levels of histidine and of the as yet unidentified 

 repressor of the histidine-degrading enzymes, together control the 

 formation and subsequent fate of histidine. If the level of histidine 

 is low, and that of the repressor is high, i.e. in the case of the organ- 

 ism growing in a glucose-containing medium without histidine, then 

 histidine will be synthesized de novo, and not degraded, but used 

 exclusively for protein synthesis. Conversely, if the level of histidine 

 is high, and that of the repressor is low, i.e. in the case of the organ- 

 ism growing in a medium containing histidine, perhaps other carbon 

 compounds, but no glucose, then histidine will not be synthesized 

 de novo and the exogenous histidine will be used in part for protein 

 synthesis, and in part degraded to provide additional energy and 

 building blocks. 



Prof. Potter spoke of the liver cell which fails to proliferate in a 

 medium that presumably contains all the metabolites the cell 

 requires for growth. He has suggested that the cell fails to grow 

 because it destroys one or more of the essential metabolites. It 

 would resemble in this case the histidine-requiring mutant of A. 

 aerogenes in an environment containing a limited supply of histidine 

 and a carbon and energy source other than glucose. In this condi- 

 tion, the intracellular level of the repressor is not high enough to 

 prevent the formation of the histidine-degrading enzymes, and the 

 histidine which is degraded cannot be replaced by synthesis de novo. 

 Consequently, not enough histidine is available for protein synthesis, 

 and the growth of the organism is restricted. 



Lehninger: To change the trend of the discussion, are these 

 instances described by Dr. Pardee and Dr. Magasanik just con- 

 venient rationalizations that can be made, in view of all these 

 facts, or is there some conscious element of biological selection during 



