NUCLEOTIDES AND COENZYMES 



acetyl CoA, will encourage other investigators to attempt the 

 synthesis of other labile or inaccessible substances such as the 

 transient coenzyme phosphates (e.g., DPN'^P), often invoked, 

 but never verified experimentally, as the initial carriers of high- 

 energy phosphate in oxidative phosphorylation at the coenzyme 

 level. 



Mechanism of Coenzyme Action 



By means of the techniques described in Section II we have 

 now arrived at a seemingly comfortable state of knowledge where 

 quite a respectable number of coenzymes have been charac- 

 terized fully as to their chemical structure and properties, and 

 have been established unequivocally as functional co-partners in 

 their respective enzymatic systems. But we are still confronted 

 with the important, and largely unanswered, question: "What 

 is the precise mechanism by which these coenzymes exert their 

 specific eflfects?" To a great extent this question is interwoven 

 with the more fundamental question, namely, the mechanism of 

 action of enzymes in general. 



It is known that enzyme-catalyzed reactions proceed with 

 lower activation energies than their counterparts wherein the 

 catalysts are H+, OH~, other ions, or organic molecules. Of 

 course, a given reaction has a fixed net change of free energy 

 associated with it, and this quantity is simply the net difference 

 of free energies between the products and reactants. A catalyst 

 cannot change the equilibrium position of such a reaction* but 

 merely hastens the rate at which the reaction proceeds by de- 

 creasing the activation energy. We are still largely ignorant of 

 how a given molecule looks in its "activated" or transition 

 state, but we may surmise that the molecule has been distorted 

 in such a way that otherwise refractory bonds are weakened or 

 positional barriers reduced, so that impacts due to ordinary ther- 



* A contradiction to this general rule is supplied by the work of Theorell 

 and Bonnichsen (39), who found that binding of substrates by high concen- 

 trations of alcohol dehydrogenase does, in fact, alter the equilibrium of the 

 reaction. 



507 



