PEPTIDES AND PROTEINS I03 



growth factors of unknown structure, and some similarities 

 with strepogenin are indicated [5]. 



Synthesis of peptides and proteins 



Owing to the paucity of available information the syn- 

 thesis of peptides and proteins can only be discussed in 

 general terms. Several suggestions have been made as to the 

 mode of formation of peptide bonds and the three most 

 likely mechanisms are those concerned with (i) the direct 

 utilization of metabolic energy, (ii) transfer reactions and 

 (iii) the reversal of proteolysis. 



Calculations based on the synthesis of dipeptides in water 

 and on the hydrolysis of dipeptides to ionic products have 

 shown that the free energy associated with the peptide bond 

 is in the range 420 to 3,000 calories [8, 25]. Though the pre- 

 cise amount may be the subject of dispute, it is clear that 

 the de novo synthesis of a peptide bond is endergonic, and 

 it is reasonable to suggest that in biological systems ATP 

 functions as a source of energy for the synthesis of peptide 

 bonds. Glutathione, glutamine, acetylsulphanilamide and 

 hippuric acid are all simple compounds containing peptide 

 or peptidic bonds and the synthesis of each of these sub- 

 stances was first observed in actively respiring preparations 

 of animal tissues. Any condition inhibiting respiration and 

 in consequence the production of energy, also inhibited 

 synthesis. The recognition of ATP as a biological carrier of 

 energy enabled the experimental systems to be greatly sim- 

 plified and studies with non-respiring cell-free preparations 

 revealed that synthesis was dependent on the presence of 

 ATP. It was observed that a new co-factor, termed Coen- 

 zyme A, played an important role in the synthesis of acetyl- 

 sulphanilamide. Coenzyme A is now known to contain 

 /5-mercaptoethylamine and to function in vivo as a carrier 

 of acetyl and other acyl groups by virtue of its ability to form 

 thiol esters. Studies with cell-free systems have shown that 

 in addition to being synthesized from acetate in the presence 

 of ATP, acetyl-Co.A can also be formed directly from an 

 acetyl donor of suitable potential without the intervention 

 of ATP, e.g. from pyruvate by the pyruvic oxidase system 



