I. ENZYMES AND THE SYNTHESIS OF 



PROTEINS 



BY JOHN H. NORTHROP' 



EVIDENCE is rapidly accumulating to show that all enzymes and at 

 least some viruses are proteins. As a result, three fundamental 

 problems, which previously appeared unrelated, may now be 

 considered as one general problem — the synthesis of proteins. 



Solution of the problem requires the explanation of a large number 

 of very precise experimental facts on the one hand, and is confined by 

 strict theoretical limits on the other. Each tissue of each species of 

 plant or animal can form its own special proteins, and these proteins are 

 characteristic of the organ as well as of the species. It is probable, there- 

 fore, that millions of different proteins exist. In some cases, as in the 

 production of antibodies, or adaptive enzymes, the presence of a foreign 

 compound may cause the organism to develop a new protein having a 

 very definite and specific relation to the compound which caused its 

 production. In other cases the presence of a foreign protein (viruses) 

 results in the formation of more of the foreign protein. The formation 

 of the type-specific nucleic acid (Avery, MacLeod, and McCarty, 1944) 

 is an example of a similar reaction. 



Whatever the mechanism of protein production, there is every reason 

 to believe it is controlled in one way or another by enzymes, and there 

 is good experimental evidence that many enzymes behave as theoretical 

 catalysts. The synthesis of proteins, therefore, must presumably obey 

 the laws of catalysis, and any hypothesis purporting to account for the 

 synthesis of proteins by means of enzyme reactions must conform to 

 the general theory of catalysis. 



The correctness of this assumption is of fundamental importance 

 since, if true, it rules out many synthetic reactions which might other- 

 wise be possible. The experimental evidence for the correctness of the 

 statement is therefore reviewed in the following section. 



I. Theory of Catalysis 



The fundamental law of catalysis was formulated by Ostwald, who 

 defined catalysts as substances which affect the rate but do not affect the 

 equilibrium state of a reaction.^ 



1 The Rockefeller Institute for Medical Research, Princeton, New Jersey. 

 2Bredig (1902) modified the definition slightly in order to make it conform more 



