The Biosynthesis of Peptide Bonds 111 



phosphate. 7 The a-amides of amino acids thus belong to a group of 

 compounds that may be loosely termed "energy-rich" amides, in anal- 

 ogy to the widespread use of the term "energy-rich" phosphate com- 

 pounds. Systematic studies do not appear to have been made to 

 determine to what extent such a-amides are present in tissues and 

 biological fluids. 



Whatever may be the mechanism whereby the exergonic cleavage of 

 ATP is coupled to the endergonic synthesis of proteins from amino 

 acids, the elucidation of this energetic coupling is only a part of the 

 total problem of protein formation. Of equal, if not greater, impor- 

 tance is the task of describing the cellular apparatus responsible for 

 the synthesis of a protein in terms of the chemical specificity that leads 

 to the characteristic arrangement of amino acid residues in the intricate 

 sequence revealed by the systematic degradation of the protein. The 

 complexity of the structure of proteins makes the biosynthesis of these 

 polymeric molecules a unique phenomenon, whose study is made for- 

 midable by the difficulties encountered in demonstrating it in cell-free 

 systems, as has been done for the biosynthesis of glycogen from glucose; 

 here, the work of the Coris and their associates has clearly established 

 the nature of the individual catalytic components of the multienzyme 

 system involved in glycogen formation. Although there is general 

 agreement that the biosynthesis of proteins is also an enzyme-catalyzed 

 process, our ignorance of its details have led to widely conflicting 

 speculations about its nature. Specifically, it is frequently argued 

 that protein synthesis does not involve a multienzyme system which 

 converts amino acids, via intermediates, to the peptide chains of a 

 protein. The proponents of this view suggest that the "activated" 

 amino acid units align themselves along a "template" (frequently con- 

 sidered to be a nucleic acid), and the alignment is followed by the 

 simultaneous formation of all the peptide bonds by an undefined cata- 

 lytic process, with the subsequent release of the completed protein 

 from the "template." It would seem that, if this is indeed the case, 

 and if it should prove impossible to dissect the enzymic apparatus 

 responsible for protein synthesis, the successes achieved in the analysis 

 of other biochemical syntheses may not be attainable in this field. 

 The question may be raised, however, whether this pessimistic view 

 is justified by the experimental evidence now available. 



Support for the "template" hypothesis has come largely from studies 

 on the incorporation of labeled amino acids into the proteins of intact 

 animals and on the formation of bacterial enzymes. Work from several 

 laboratories has demonstrated conclusively that, if one or more isotopic 



