108 THE BIOSYNTHESIS OF PROTEINS 



Lipmann, 1960). Evidence for the participation of the so-called S-protein 

 (Sachs, 1957) or of some — SH containing protein at this stage was ob- 

 tained by vonderDecken and Hultin (1960) and by Hulsmann and Lipmann, 

 1960. In certain bacteria, the transfer is inhibited by chloramphenicol (Lacks 

 and Gros, 1959), streptomycin (Erdos and Ullmann, 1959) or puromycin 

 (Yarmolinski and de la Haba, 1959). 



No doubt, the most obscure steps in protein synthesis are here, and 

 unfortunately this is the heart of the matter. The amino acids on soluble 

 RNA are bound in an activated state to specific carriers, but they are still 

 isolated from one another. The next step must be their condensation into 

 the genetically controlled sequence. Before venturing in considerations 

 upon this still completely mysterious process, let us return to the present 

 scheme of amino acid activation and examine how much confidence we can 

 place in it. 



There is no doubt that amino acids can follow this pathway and be 

 incorporated into polypeptides. Most amino acids can be activated by 

 specific 'activation enzymes' and transferred to specific ribonucleic 

 acceptors; these in turn will loose the bound amino acids, which will 

 eventually be recovered as polypeptides in the ribosome fraction. If an 

 aminoacyl adenylate on the activation enzyme is labelled in the carboxyl 

 by 1^0, heavy oxygen is later found in the proteins (Boyer and Stulberg, 

 1958). Molecules of the amino acid which had been activated by this 

 process were therefore used in making proteins. The ubiquity of the 

 activation enzymes indicates that they fulfil a quite general function com- 

 mon to all kinds of cells of animals, plants and bacteria. A more convincing 

 indication in favour of the importance of activation enzymes for protein 

 synthesis was obtained by Sharon and Lipmann (1957): several tryptophan 

 analogues are known to be incorporated instead of tryptophan into the 

 proteins of micro-organisms and animal tissues, whereas other tryptophan 

 analogues are not incorporated. It is a striking fact that the analogues which 

 are incorporated are those which are activated by the pure enzyme. This 

 identical specificity of the activation enzyme and of protein synthesis as a 

 whole, is good circumstantial evidence for the participation of this activa- 

 tion enzyme in protein synthesis. The mistakes made by this enzyme are 

 reflected in the protein formed. 



The exact function of soluble RNA in the process is not completely 

 clarified. It can act as a depositary of activated amino acids. But one may 

 wonder whether its function resembles more that of a store-house in a 

 side street or that of a carrier of amino acids on the highway. In support of a 

 function of carrier or obligatory intermediate, one may quote the rapid 

 inhibition of protein synthesis by ribonuclease, which is known to degrade 

 soluble RNA rapidly and to act more slowly on microsomal RNA (Brachet 

 and Six, 1959). The experiments upon which the classical scheme of pro- 



