FRITZ LIPMANN 



with the elimination of a molecule of pyrophosphate (1,3,12,18), 

 while phosphorolysis apparently leads in some manner to the 

 formation of acyl phosphate with elimination of nucleoside 

 diphosphate (NDP) (5,7,13,21). In other words, the pyro- 

 phosphate elimination represents an activation through linking 

 the carboxyl to the nucleoside by way of a monophosphate bridge, 

 forming an NMP^^acyl. On the other hand, phosphorolysis 

 seems to represent a discarding of the nucleotidic part of the 

 energy carrier and a more or less direct linking of the carboxyl to 

 the phosphate (5,13). Such a pyrophosphate elimination scheme 

 was first observed in a CoA-linked acyl activation. A similar 

 mechanism appears to apply to the synthesis of the peptidic bond 

 in pantothenic acid (18). But more important, an analogous 

 mechanism has now been found to operate in the activation of 

 normal amino acids (11). In both cases, the acyl '^phosphonu- 

 cleotide seems not to be freely diffusible but rather tightly 

 linked to the activating protein. This interpretation is mainly 

 based on isotope exchange reactions and should rather be con- 

 sidered as somewhat preliminary. Nevertheless, it may serve as 

 background for a discussion of the mechanism of peptide bond 

 formation in protein synthesis. 



Protein Synthesis 



With this still sketchy information on mechanisms for 

 peptide bond synthesis, we now proceed much less securely to 

 possible mechanisms of lining up the different amino acids into a 

 specific protein pattern. Sequential arrangement of the amino 

 acids obviously is the dominant problem before us. If the 

 apparatus is available to line up a predetermined sequence of 

 amino acids most of which will be quite long, twenty, forty, or 

 more links, the final shaping of the molecule might be expected 

 to be wholly or partly a spontaneous one. In any case, this 

 phase of final shaping will be neglected at the present, and our 

 focus will be exclusively on sequential arrangement as a back- 

 ground for specificity, even though this almost certainly is a 

 somewhat precarious simplification. 



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