94 THE BIOSYNTHESIS OF PROTEINS 



/)-fluorophenylalanine suppresses the synthesis of enzymes and depresses 

 the incorporation of phenylalanine ; but it does not affect the incorporation 

 of the other amino acids (Halvorson and Spiegelman, 1952; Rabinovitzeia/., 

 1954). The first interpretation of these facts was that the amino acid ana- 

 logue blocks phenylalanine utilization and net protein synthesis, and that 

 the unaffected incorporation of the other amino acids must therefore be due 

 to an exchange process. This interpretation later proved incorrect ; actually, 

 ^-fluorophenylalanine does not prevent protein synthesis, it competes with 

 phenylalanine and it is incorporated into proteins instead of the normal 

 amino acid (Baker et ah, 1954; Munier and Cohen, 1956, 1959; Kerridge, 

 1959; Vaughan and Steinberg, 1960; Richmond, 1960). The incorporation 

 of all the other amino acids in the presence of the analogue is due to net 

 synthesis of abnormal proteins in which a large part of the phenylalanine is 

 replaced by the analogue. Many of the abnormal enzymes made in the 

 presence of fluorophenylalanine are inactive, hence the observation that the 

 synthesis of enzymes (as measured by the increase of enzymic activity) is 

 inhibited. Other amino acid analogues act in the same way (Sharon and 

 Lipmann, 1957; Pardee etal, 1957; Brawerman and Yeas, 1957; Gross and 

 Tarver, 1955; Vaughan and Steinberg, 1959; Munier and Cohen, 1959; 

 Cowie and Cohen, 1957 ; Cohen et ah, 1958 ; Rabinovitz ef «/., 1955). Clearly, 

 there is no reason to call upon exchange processes for explaining the experi- 

 mental results. 



Another group of observations which were regarded as direct evidence 

 for exchange processes was made by Gale (1957) on disrupted Staphylo- 

 cocci. The time curve of the incorporation of glutamic acid into acid 

 insoluble compounds is not the same when glutamic acid is added alone or 

 together with all the other amino acids. When a mixture of amino acids is 

 provided, the incorporation is linear and largely irreversible, for the 

 addition of non-labelled glutamic acid causes no loss of incorporated I'^C. 

 To the contrary when the system is presented with glutamic acid alone, 

 incorporation is fast but it rapidly stops ; the time curve resembles a satura- 

 tion or adsorption curve. Moreover, non-labelled glutamic acid causes a 

 release of part of the previously incorporated labelled compound, indicat- 

 ing a replacement by mere exchange (Gale, 1957). These facts, no doubt, 

 were well observed but their interpretation at present must be re-examined ; 

 at the time they were made, the existence of soluble RNA and its capacity 

 of binding amino acids reversibly was not known ; it is possible that part 

 of the exchangeable glutamic acid was bound in this way or at the end of 

 polypeptide (Webster, 1959). It was not known either that in bacterial 

 preparations amino acids can be incorporated into peptide constituents of 

 cell wall material (Mandelstam and Roger, 1958; Chantrenne and Devreux, 

 1958, 1960; Hancock and Park, 1958; Richmond, 1959; Roodyn and 

 Mandel, 1960) and it would seem that part of the glycine or glutamic acid 



