450 F. GROS 



crease, the internal concentration of amino acids tends to decrease, and 

 therefore the rate of RNA synthesis also decreases. This should lead to a 

 decrease in the rate of protein formation. This kind of control however, is 

 not very efficient owing to the catalytic nature of the role exercised by amino 

 acids in RNA synthesis 28 (see also the discussion by Magasanik et a/. 139 ). 



The rate at which protein precursors are produced offers a much more 

 direct method of control of the rate of protein formation. It has, for example, 

 already been shown that a given metabolite inhibits the activity of, or 

 represses the synthesis of, the enzymes which catalyze its own forma- 

 tion 205 ~ 209 



Although enzyme repression is certainly not as efficient for controlling 

 the immediate supply of protein precursors as is the inhibition of the ac- 

 tivity of biosynthetic enzymes, this phenomenon in itself poses very inter- 

 esting problems concerning the interaction of a metabolite with the pro- 

 tein-forming machinery. 



Thus, repression does not usually concern the synthesis of only one en- 

 zyme in the metabolic sequence, but of many or of all of the enzymes of 

 the chain. 210 How can a metabolite of simple structure regulate the rate of 

 synthesis of many specific proteins with very different affinities for it? 

 What is the exact nature of the endogenous repressor, and at what stage of 

 protein biosynthesis does it act? 



A discussion of these problems would be too far reaching at the present 

 time, but repression is certainly one of the most complex and most inter- 

 esting problems in relation to the biosynthesis of protein in the intact cell. 



VII. Addendum 



Since the writing of our article, a great number of new experiments have 

 shed light on some points of main importance in the problem of protein 

 synthesis. 



For instance, Roberts and his group 211 have finally succeeded in showing 

 that very short contact (about 10 seconds) of logarithmically growing cells 

 of E. coli with S 35 -labeled sulfate leads to early appearance of radioactivity 

 in the ribosome fraction, and that such labeling precedes the one of the 



205 H. J. Vogel, "The Chemical Basis of Heredity" (W. D. McElroy and B. Glass,, 

 eds.), p. 276. Johns Hopkins Press, Baltimore, 1957. 



206 A. B. Pardee, in "The Regulation of Cell Metabolism," A Ciba Symposium, p. 

 295. Churchill, London 1959. 



207 J. Monod and G. Cohen-Bazire, Compt. rend. acad. sci. 236, 746 (1953). 



208 M. Cohn, G. N. Cohen, and J. Monod, Compt. rend. acad. sci. 236, 746 (1953). 



209 W. Maas and L. Gorini, Federation Proc. 16, 215 (1957). 



210 G. Cohen and Jacob, Compt. rend. acad. sci. 248, 3490 (1959). 



211 E. T. Bolton, R. J. Britten, U. B. Cowic, B. J. McCarthy, K. McQuillen, and R. B. 

 Roberts, Carnegie Institution Year Book 58, p. 259 (1958-1959). 



