lO JOHN H. NORTHROP 



thesis of proteins would be associated with some type of structure such as 

 is present in cells which would provide the necessary surface. 



This hypothesis solves both the energy and the specificity problem 

 and appears to be the most reasonable and simplest mechanism so far 

 suggested. It deserves the most careful consideration. The accumulation 

 of protein in the surface layer is an undoubted fact, so that only the 

 specific synthesis is in doubt. Unfortunately no experimental verification 

 has been obtained as yet for this step. It must be remembered, however, 

 that negative results are very unconvincing in experiments of this type, 

 since even after positive results have been reported it is sometimes 

 necessary for the problem to be studied for years before conditions are 

 sufficiently well established so that the results may be obtained at will. 



Synthesis by the Addition of Energy 



Coupled Reactions. Many cases are known in which a reaction 

 which requires energy and hence does not occur alone will take place if 

 another reaction which liberates energy takes place simultaneously. Such 

 reactions control carbohydrate metabolism (Meyerhof, 1944; and Kal- 

 ckar, 1944). In these reactions part of the energy liberated by hydrolysis 

 or oxidation is used for a synthetic reaction so that, although the total 

 change results in the liberation of energy, some steps occur which require 

 energy. Each step is controlled by a special enzyme. Phosphoric acid 

 esters are concerned in these energy exchanges and it is reasonable to 

 suppose that similar esters may take part in the synthesis of proteins, as 

 Bergmann and Fruton (1944) have suggested. Many other possible 

 sources of energy exist, but no direct experimental evidence has been 

 found to connect the synthetic and energy-providing reaction. The syn- 

 thesis of hippuric acid from glycine and benzoic acid in the presence of 

 liver slices is perhaps the nearest approach to such a reaction. Borsook 

 and Dubnoff (1940) found that rapid synthesis occurred in the presence 

 of intact liver cells. Extracts or even minced tissue failed to cause the 

 reaction.'' It seemed evident that the energy was obtained from respira- 

 tion and hence that the reaction would stop if the respiration were 

 stopped, and hydrolysis should then occur instead of synthesis. Addition 

 of HCN, which poisons the respiratory enzymes, did stop synthesis, but 

 it also stopped hydrolysis. This disconcerting result may be due to 

 poisoning of the enzyme which catalyzes the benzoic acid reaction, al- 



4 It is perhaps significant that the three fundamental reactions, protein synthesis, 

 photosynthesis, and fixation of nitrogen all require energy and all are so far inseparable 

 from intact cells. 



