The Biosynthesis of Peptide Bonds 113 



Of special importance in regard to the question whether peptides are 

 intermediates in protein synthesis are the experiments of Anfinsen and 

 his associates, who have studied the incorporation of labeled amino 

 acids into ovalbumin by minced hen oviduct or into insulin and ribo- 

 nuclease by beef pancreas slices." In contrast to the results of in vivo 

 studies, the residues of a given amino acid were found to be unequally 

 labeled along the peptide chain of each of these proteins, a finding 

 consistent with the view that peptides are metabolic intermediates 

 between amino acids and proteins. Anfinsen has suggested that the 

 apparent discrepancy between the results of in vivo and in vitro ex- 

 periments may be ascribed to differences in the rates of metabolic 

 reactions in the two types of systems. It would seem inescapable that 

 the removal of a tissue from the intact animal would lead to a pro- 

 found alteration in the rates of those enzymic processes that are influ- 

 enced by such factors as hormonal regulation and normal blood flow. 

 Thus far, no one has reported comparative experiments, at several 

 time intervals, in which a labeled amino acid was incorporated into 

 the same protein in vivo and in vitro and the pattern of labeling along 

 the peptide chain was determined in each case. Such studies are needed 

 to clarify the discrepancy between the results obtained in the living 

 animal and in tissue preparations. 



Clearly, the available data on amino acid incorporation into proteins 

 do not permit one to draw any definite conclusions about the chemical 

 pathways of protein synthesis. However, it would seem more likely 

 that useful clues will come from the continued study of those biological 

 systems in which non-uniform labeling of peptide chains is observed 

 and where one may expect the occurrence of well-defined intermediates 

 between amino acids and proteins. It is frequently stated that peptides 

 (other than glutathione, carnosine, etc.) are not present to a measur- 

 able extent in mammalian or bacterial cells, but the validity of this 

 assertion may be questioned, since it cannot be reconciled with the 

 numerous reports in the literature on the isolation or identification of 

 peptide material from animals, plants, and microorganisms. 1 '- Where 

 negative results have been obtained in the search for peptides as 

 cellular constituents, the possibility must be considered that the meth- 

 ods applied were not adequate; for example, because of failure to react 

 with ninhydrin or because of tight binding to the cellular proteins. 

 Also, the question of the variations in the peptide level, which may 

 depend on the physiological state of the cell, may be of importance 

 but cannot he properly assessed at present. A logical difficulty in the 



