THE SYNTHESIS OF PROTEINS I3 



Formation of Native as Distinct from Denatured Proteins 



It was stated earlier in this discussion that the reaction, protein and 

 water ^ amino acids is nearly complete and very little protein remains 

 at equilibrium. This is experimentally true in the case of denatured 

 proteins but merely an assumption as far as native proteins are con- 

 cerned. Most native proteins are digested very slowly by proteases and it 

 is possible to assume, as Linderstrom-Lang and Jacobsen (1941) have 

 suggested, that the first step in the hydrolysis is the formation of dena- 

 tured protein from the native protein. Linderstrom-Lang attempted to 

 answer the question by a study of the temperature coefficient of hy- 

 drolysis of native and denatured protein, but the results were inconclu- 

 sive. The hydrolysis of a protein like trypsin or chymotrypsin, which 

 exists in an equilibrium between native and denatured forms (Northrop, 

 1939), should furnish evidence in this connection. 



Haurowitz and collaborators (1945) have reported that globular 

 proteins, such as egg albumin and serum globulin, are not hydrolyzed 

 by trypsin unless they are denatured, whereas "fibrous" proteins, such 

 as fibrin and myosin, are hydrolyzed at about the same rate in either 

 native or denatured forms. 



If enzymatic hydrolysis does require preliminary denaturation, then 

 it could be assumed that native proteins can be synthesized without 

 adding energy, i.e. by a purely catalytic reaction. Energy is required to 

 denature the protein which then hydrolyzes with the liberation of energy. 

 The entire cycle would require three reactions : 



enzyme 



1. Amino acids ^ native protein + energy. 



2. Native protein + energy ^ denatured protein. 



enzyme 



3. Denatured protein ^ amino acids + energy. 



It is also possible to assume that denatured protein is formed first 

 from the amino acids and that the native proteins are then formed from 

 this denatured protein. This cycle would be as follows : 



Amino acids + energy ^ denatured protein 

 Denatured ^ native protein + energy 



The direction in which the reactions proceed is determined by the 

 energy changes and the rate of the reaction by the enzymes present. 



