486 ANIMAL BIOCHEMISTRY 



Requirements 



The overall problem of protein biosynthesis appears to resolve into 

 three general requirements. The first of these involves the necessary 

 raw materials, the amino acids. Since proteins are readily hydrolyzed 

 to amino acids and obviously are combinations of these materials, 

 at least to a large extent, it has always been assumed that amino acids 

 are actually combined somehow in forming proteins. The other 

 possibility, that another type of unit condenses and is later converted 

 to the amino acid, has never been considered seriously. More recently, 

 experiments justify this attitude with the finding that isotopically 

 labeled amino acids actually appear as such in the proteins of cells. 

 Hence amino acids may be directly involved although it is still 

 possible that they are first converted to some sort of derivative before 

 condensation to protein. The necessary amino acids in the case of 

 animals come directly from the diet and from the metabolic processes 

 of the cells. The factors concerned in maintaining this supply have 

 already been considered. 



The second requirement for protein synthesis is the combination 

 of amino acids with the formation of the peptide bond. This reac- 

 tion is simple enough on the face of it but does not tend to go spon- 

 taneously. With a positive free-energy change of this magnitude, the 



R R' 



I I 



+H3NCHCOO- + +H3NCHCOO- i^ 



R R' 



1 I 



+H3NCHCONHCHCOO- + H2O AF^ +3,000 cal. 



equilibrium is far in the direction of hydrolysis, especially in view 

 of the high water concentration customary in biological tissues. Since 

 all proteins contain many peptide bonds, they are very unstable as a 

 whole with respect to hydrolysis and can form only when some coupled 

 system supplies the free energy needed to drive the condensation. 

 Some workers in the field believe that less energy is needed to form 

 each subsequent peptide bond as the chain gets longer. However, this 

 possibility does not remove the free-energy requirement; it merely 

 reduces it, and the basic problem is still unchanged. 



Obviously some system is needed to activate the amino acids t)r 

 ])erhaps the growing peptide chain. One of the most interesting possi- 

 bilities depends upon the formation of amino acid phosphates. These 



