98 C. B. VAN NIEL 



primary approach to the problems of syntheses and growth. Biochemists 

 in particular have come to recognize that the thermodynamic formula- 

 tions beg the question which has become paramount in today's bio- 

 chemistry, viz. that of the mechanism whereby the result is achieved. 

 Applied to the problem under discussion, this means that the concept of 

 an energetic coupling between synthesis and breakdown, no matter how 

 sound fundamentally, is too vague to be permanently satisfactory, and 

 that ultimately our task is to discover the mechanisms whereby such 

 coupling is accomplished. 



The most fruitful hypothesis that has been advanced in this connec- 

 tion assumes the existence of material links between breakdown and 

 synthesis. It may, somewhat primitively perhaps, be paraphrased in 

 this manner : instead of regarding biological syntheses as very special 

 processes which, because they require energy, are basically different 

 from the breakdown reactions in which energy is liberated, it would be 

 more appropriate to describe syntheses as series of enzyme-controlled 

 step reactions, each step comparable in every way but one with those 

 which collectively compose the breakdown. The differentiating feature 

 is that, whereas the breakdown reactions can always start with any one 

 of the utilizable substrates in the food, the synthetic processes require 

 particular substances which are not usually provided but which arise 

 from the initial substrates as intermediate products in the normal course 

 of their metabolic degradation. Such products are characterized by being 

 more unstable, i.e. more reactive, than their ultimate precursors, the 

 foodstuffs proper, thus implying that their energy level has been raised 

 with respect to the initial materials. 



This concept, first enunciated by Kluyver (22, 23) some fifteen years 

 ago, does not conflict with the earlier one of energetic coupling. Its great 

 value lies in the penetrating insistence upon the functioning of an in- 

 telligible chemical mechanism which is capable of accounting for the 

 transfer of energy. 



During the past few years tremendous strides have been made in this 

 direction. Ranking high among these is the discovery of the phosphory- 

 lated carbohydrate now known as "Cori-ester," a compound which can 

 serve as the immediate raw material for the spontaneous enzymatic syn- 

 thesis of a number of di- and polysaccharides (24-30). No less signifi- 

 cant are the studies of Lipmann (31, 32) on the labile intermediary 

 metabolic products characterized by a high-energy phosphate bond. It 

 has now been shown that these substances, too, can be used for per- 



