STRUCTURAL AND CHEMICAL ARCHITECTURE OF HOST CELLS 175 



It may be asked if these facts indicate a stepwise addition of amino acids 

 to form peptides and proteins. It is significant that in these isolated systems 

 individual amino acids can be incorporated into peptide linkage without the 

 simultaneous presence of other amino acids and their simultaneous incorpora- 

 tion into protein. However, there is no indication at the present time of the 

 size of the newly formed peptide units in the ribonucleoprotein of the micro- 

 somal fraction, nor is the relation of such peptide formation to normal protein 

 synthesis entirely clear. It is known in animal cells and microorganisms that 

 deficiencies with respect to single essential amino acids block all amino acid 

 incorporation (Borsook et at., 1957) suggesting either the essentiality of inte- 

 grated simultaneity in protein synthesis or the existence of requirements for 

 specific amino acids as acceptors in the development of peptide chains. Thus, 

 the so-called protein syntheses studied so far with single amino acids may be 

 more akui to the polymerization of leucine to polypeptides of 3 to 20 amino 

 acids when the phosphate anhydride of leucine is permitted to stand in 

 aqueous solution at room temperature (Katchalsky and Paecht, 1954). 



The problem of whether amino acids form low molecular peptides on the 

 way to protein or are simultaneously zippered to form a polypeptide chain is 

 an outstandmg problem of protein synthesis. In problems such as the ap- 

 parent conversion of milk protein to plasma protein in the rat, a great deal 

 of work has been done to determine whether peptides may be derived intact 

 from the milk protein. As reviewed by Campbell and Stone (1957), it is con- 

 sidered that there is little evidence that such an interconversion occurs at a 

 level above that of the free amino acids. However, contrary views are held 

 by a variety of workers. For example, Ebert (1954) and Walter et al. (1956) 

 consider that large specific peptides and proteins are derived from the organ 

 fragments used as transplants in studies of grafts and embryogenesis. 



No abnormal accumulation of intermediate peptides has yet been seen 

 under experimental conditions of amino acid deficiency (Halvorson and 

 Spiegelman, 1952) although the existence of soluble peptides in various 

 organisms, e.g. blue-green algae, has long been recognized. However, the 

 existence of very small amoimts of soluble intermediates in fatty acid meta- 

 bolism could not be detected for many years. As an alternate hypothesis it 

 may be supposed that low molecular peptides are formed at the microsome 

 surfaces. Koningsberger et al. (1957) have recently described the existence 

 of nucleotide-bound carboxyl-activated peptides on ribonucleoprotein par- 

 ticles of yeast. The fact that in some instances peptides support growth 

 requirements of mutant organisms somewhat better than do free amino 

 acids may bear on this problem (Simmonds and Fruton, 1949; Simmonds and 

 MiUer, 1957). 



One approach to this problem has involved an attempt to see if an amino 

 acid derived from different parts of a protein possesses identical isotope 



VOL, 1—13 



