S/nXK) 1'. \ ELICK 



KM) 





y3 



oC 



Fig. 1. Folded conformations of DPNH with a and /3 isomerism at the pyridine- 

 N-riboside bond. Tliese are projections of skeletal models in which the planes of 

 the nitrogen rings are parallel to the plane of the paper, nicotinamide above and 

 adenine below. Juxtaposition of the rings accounts for the excitation energy 

 transfer, but in the absence of more detailed information the mutual orientations 

 of the rings are arbitrary. Other bonds are out of plane and hence appear of 

 varying length in projection. Note the drastic effect of the a-j3 isomerism on the 

 conformation of the ribose diphosphate moiety. It is to be observed also that 

 the two hvdrogens at pyridine-C-4 in a folded structure are not chemically 

 ecjiiivalent. 



that the reaction is a stereospecific transhydrogeiiation between sub- 

 strate and pyridine ring, presumably involving the transfer of a 

 hydride ion. There has been singularly little chemical study of re- 

 ducible pyridine derivatives, and nearly twenty years elapsed between 

 the work of Warburg and the observation by Pullman, San Pietro, 

 and Colowick (18) that the enzymatic reduction occurs at the 1,4 

 and not at the 1,2 or 1,6 positions in the pyridine ring. 



Substitution on the ring nitrogen is essential for the oxidation re- 

 duction behavior of the nicotinamide, and nature has selected for 

 this purpose adenosine diphosphate ribose. Why so extended a struc- 

 ture is needed is not certain and is one of the problems that con- 

 cerns us. The dinucleotide contains four ring structures connected by 

 ten bonds around which free rotations may occur. There are, there- 

 fore, many possible spatial conformations. Only one of these con- 

 formations should occur in a given enzyme complex, and certain ones 

 of them should be more stable than others in free solution. 



