38. BIOSYNTHESIS OF PROTEINS IN BACTERIAL CELLS 435 



These observations show that no discrimination can be made between 

 inducible and constitutive enzymes in respect of their sensitivity to the 

 base analogs and do not favor the interpretation of an obligatory cosyn- 

 thesis between inducible enzymes and specific RNA. 



(3) The main problem, therefore, in the mechanism of action of the 

 analogs, is not to explain why they influence inducible rather than constitu- 

 tive synthesis of enzymes but, rather, why they inhibit the synthesis of a 

 specific enzyme protein without modifying appreciably the synthesis of 

 total protein (growth). 



A possible explanation is that the analog modifies the specificity of the 

 stable RNA templates. These templates could still function in the building 

 of a peptide chain; but this peptide chain would lack biological specificity. 

 This hypothesis would be supported by the fact that the RNA of virus 

 particles which contain thiouracil loses its infectivity. 145 



Such an interpretation cannot be retained however for purely kinetic 

 reasons; in most of the cases studied, the synthesis of enzymes 151, 152 is 

 inhibited selectively, as soon as the analog is added. Since we know that 

 the RNA particle is metabolically stable, the RNA templates existing prior 

 to the addition of the analog should go on catalyzing enzyme formation. 

 Enzyme synthesis should be inhibited only after a lag period corresponding 

 to the time required for the accumulation of the altered templates. 



Chantrenne put foward the hypothesis that the inhibitory effect of the 

 analog on enzyme synthesis could be based on a mechanism other than 

 alteration of the RNA templates and suggested that base analogs could be 

 incorporated very rapidly into an RNA fraction capable of very active 

 renewal, such as the sRNA, and this would explain their immediate effect 

 on the synthesis of certain proteins. 153 



Recent results on the metabolic effects of 5-fluorouracil in E. coli are in 

 good agreement with Chant renne's hypothesis. 154 The addition of 5-fluoro- 

 uracil to E. coli, growing exponentially, diminishes within 1 minute the 

 relative rates of incorporation of proline and of tyrosine into the protein, 

 stimulates the rate of incorporation of arginine, and does not influence 

 appreciably the incorporation of fourteen other amino acids (the diminu- 

 tions observed for proline and tyrosine are, respectively, 27 and 20%). 

 Similar specificity appears to exist at the level of the fixation to the RNA. 

 Amongst seven amino acids tested (valine, methionine, phenylalanine, ar- 

 ginine, isoleucine, proline, and tyrosine) only proline and tyrosine are af- 

 fected in rate and extent of fixation to the RNA. The saturation level of 

 the RNA proline pool is lowered by about one-third, that of the RNA 



153 H. Chantrenne, Biochem. Pharmacol. 1, 233 (1959). 



154 S. Naono and F. Gros, Compt. rend. acad. sci. (1960), in press. 



