FRANK M. HUENNEKENS 



would lead only to the fruitless position of inspecting the struc- 

 ture of biologically active agents in the hope of understanding 

 their mechanism of action. The remainder of the molecule is 

 concerned then, in all probability, with the binding of the 

 coenzyme to the protein. Thus, DPN and TPN have the same 

 oxidation potentials and undoubtedly could replace each other 

 as hydrogen carriers, except for the rigid structural require- 

 ments — undoubtedly a reflection of some control mechanism — 

 for binding to the appropriate apoenzyme. Again, one need not 

 invoke any special function of the uridine molecule as a carrier of 

 activated sugar groups or cytidine for choline; probably each 

 could replace the other in an energetic sense were it not for the 

 binding requirement. 



These remarks are not meant to imply that the portion of 

 the coenzyme carrying the functional group is not also involved 

 in binding. The inhibition of FAD-protein binding by ribo- 

 flavin, and the loss of fluorescence when FAD is bound to 

 enzymes, interpreted as a linkage between the N-3 position on 

 the isoalloxazine ring and the protein, are evidence for this 

 point. Since many coenzymes have in common a simple 

 mononucleotide structure, or the components thereof, it would 

 appear instructive to examine, from both a thermodynamic and 

 kinetic view, the binding of a typical mononucleotide, e.g., AMP, 

 by various model peptides. In the event that no binding could 

 be found to approximate that of typical coenzymes and apo- 

 enzymes, this, in itself, might be considered as preliminary 

 evidence for "cage" type of binding, where the total binding is 

 more than the sum of individual group effects. 



The plain fact is that, at present, very little is known about 

 the manner in which coenzymes are bound to proteins. In 

 order to understand this type of binding we need to have infor- 

 mation about the reactive groups and topography of both com- 

 ponents. In the latter case this is indeed a formidable under- 

 taking, and progress has been understandably slow. However, 

 with the availability of pure, crystalline nucleotides and the 

 adoption of physical methods we are being presented now with 



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