G. ROBERT GREENBERG 



REVERSIBLE SYSTEMS 



It may be found that the equihbrium constant of a reaction 

 does not favor synthesis of an intermediate compound. The 

 resulting situation might be presented as : 



C ^ -1 J ' P 



Suppose that the equihbrium of C ^ J Hes far toward G such 

 that at equihbrium J is present in approximately 1/1000 the 

 concentration of C, and suppose that the rate of C — ^ J < J -^ P. 

 Thus J would not accumulate. It follows that if the reaction 

 proceeds to P, then J -^ P lies to the right and the change in free 

 energy of the over-all reaction is negative. This situation 

 appears to be common in biochemical mechanisms. Consider 

 the activation of formate which has been found to proceed by 

 the following over-all reaction (13,14). 



HCOOH + FAH4 + ATP , Ni«-CHOFAH4 + ADP + Pi 



Formate appears to be reversibly incorporated, for when a suit- 

 able formyl acceptor (5-amino-4-imidazolecarboxamide ribo- 

 tide) is added the rate of incorporation of formate can be in- 

 creased several times. This reversibility is also inherent in the 

 studies of Schulman and Buchanan (25). Although it seemed 

 possible that this reaction was more complex (as, for example, 

 enzyme-substrate compounds), the mechanism was first con- 

 sidered as follows : 



FAH4 + ATP , FAH4— P + ADP 



FAH4— P + HCOOH , Ni''-CHOFAH4 + Pi 



Equally possible was the reaction of ATP and formate 

 first. 



No labile phosphate was formed unless all of the substrates 

 were present. This was true even when the phosphoenolpyruvate 

 to pyruvate system was added to convert ADP to ATP in order 

 to draw the first reaction in the forward direction. Accordingly 

 the mechanism of the reaction remains obscure. However, if the 

 over-all equilibrium constant is about 1, then the first reaction, 



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