HYDROLYSIS OF PEPTIDE BONDS 



Another mechanism for favoring the formation of peptide bonds 

 IS coupling the synthetic reaction with another cnergy-yiekHng chemical 

 reaction. At the present writing, few experimentally demonstrated 

 examples of such coupling can be cited (4). Surely the careful study 

 of the coupling between peptide synthesis and energy-yielding systems 

 represents one of the most interesting directions for future research; 

 cj. Bergmann and Fruton (11). 



Before leaving the question of the role of the proteolytic en- 

 zymes in peptide synthesis, it should be emphasized that the available 

 experimental knowledge does not yet permit the conclusion that re- 

 versal of proteolysis is actually the process employed in biological 

 systems for the synthesis of peptide bonds. It is well to remember that 

 in the metabolic transformation of the polysaccharides, for example, 

 synthesis is not effected by the reversal of the hydrolytic action of the 

 amylases, but rather through a different chemical pathway, namely, 

 the synthetic action of the phosphorylases (16). The intervention of 

 phosphate in the biosynthesis of peptides also has been suggested (23), 

 but no experimental evidence for this view has as yet been brought 

 forward. Other speculations concerning the biological mechanisms 

 for peptide synthesis have been advanced, largely on the basis of 

 in vitro reactions (11). Clearly a greater fund of data on coupled 

 reactions in metabolic systems is required before it will be possible to 

 decide which, if any, of these theories is correct. 



Perhaps the strongest reason for assuming, as a working hy- 

 pothesis, the view that proteolytic enzymes do play an important 

 role in protein synthesis is the fact they are the only known biocatalysts 

 which, by virtue of their sharp specificity, could direct, precisely and 

 reproducibly, the coupled sequence of successive peptide syntheses 

 required for the formation of a protein. The considerations concerning 

 specificity which have been discussed earlier in this article cannot fail 

 to modify our picture of the possible role of the proteolytic enzymes 

 in the biological synthesis of proteins. Until a few years ago, intra- 

 cellular proteolytic enzymes, such as papain or cathepsin, were re- 

 garded either as single enzymes or mixtures of very few enzymes. On 

 this basis it was concluded that the specificity of a single enzyme can 

 predetermine the molecular pattern of a protein. Thus it was assumed 

 that the specificity range of an intracellular proteinase would be suffi- 

 ciendy broad to comprise all the peptide bonds present in a protein 



