The Biosynthesis of 

 Peptide Bonds 



JOSEPH S. FRUTOIN 



Few current biochemical problems have evoked more imaginative 

 speculation or animated discussion than the elucidation of the met- 

 abolic pathways in the biosynthesis of proteins. The challenge of this 

 problem is a consequence not only of the central place of the proteins 

 in the dynamics of living matter but also of the conceptual and experi- 

 mental difficulties that it has presented. Since there is general agree- 

 ment that the principal mode of linkage between the individual amino 

 acid units of a protein is the CO-NH bond, the most profitable discus- 

 sion has centered about the cellular mechanisms for the synthesis of 

 such bonds. However, in limiting ourselves to the consideration of 

 peptide bond synthesis, it is recognized that the characteristic proper- 

 ties of proteins also depend on the integrity of other linkages and that, 

 in protein formation, the synthesis of peptide chains may be closely 

 linked to the creation of these accessory bonds. 



It has long been known from physiological studies that the forma- 

 tion of proteins from amino acids requires energy and that this energy 

 is largely derived, in higher organisms, from the oxidative degradation 

 of carbohydrates and fats. However, the means whereby this energy 

 transfer occurs is still unknown, although there is excellent evidence 

 for the view that it involves the coupling of oxidation to the synthesis 

 of the pyrophosphate bonds of adenosine triphosphate (ATP) and the 

 coupling of the cleavage of ATP to peptide synthesis. Before consider- 

 ing possible ways in which ATP may play a role in peptide bond 

 synthesis, it will be useful to discuss some of the available knowledge 

 about the energy changes in the formation and cleavage of CO-NH 

 linkages. 



For many years, it was customary to assign the value of about -f3 

 kcal. per mole to the standard free-energy change (&F°) in the con- 



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