20 A SYMPOSIUM ON RESPIRATORY ENZYMES 



be looked upon as a highly specific electron acceptor. Dixon and 

 Zervas (11) favor this view and have presented evidence that several 

 compounds can substitute for the pyridine nucleotide as electron 

 acceptors. They have shown, for example, that alloxan can be re- 

 duced by malate or alcohol in the absence of the so-called pyridine 

 nucleotide coenzyme, the specific protein alone being present. 

 Whether alloxan plays such a role as an electron acceptor in living 

 tissues is an open question. The observation of Jacobs (15) that the 

 injection of alloxan into rabbits produced hypoglycemic convulsions 

 is suggestive in view of the role of the pyridine nucleotides in sugar 

 metabolism. Further evidence that the pyridine nucleotides are 

 highly specialized electron acceptors is the fact that they participate 

 in reactions in which the substrates possess markedly different 

 chemical properties. Moreover, they show no great affinity for the 

 specific protein also concerned in the reaction. Whatever their role, 

 we know that the result of the reaction is the reduction of the 

 pyridine nucleotide and the formation of the oxidized product of the 

 substrate. The latter may in turn act as the substrate in another oxi- 

 dation in which the same pyridine nucleotide is involved but with 

 another specific protein. 



Now in order that the pyridine nucleotide may act as a catalyst 

 the reduced form must be reoxidized. The reduced pyridine nucleo- 

 tides are, however, not unlike the substrates themselves in that they 

 react sluggishly with most oxidizing agents. In the living cell they 

 appear to be oxidized readily by only one specific class of sub- 

 stances, the flavoproteins. In this reaction two electrons and one 

 hydrogen ion from the reduced pyridine nucleotide are transferred, 

 along with a hydrogen ion from the environment, to the flavin por- 

 tion of the flavoprotein. Whether the protein part of the flavoprotein 

 functions by activating the sluggish reduced pyridine nucleotide is 

 not known, though these flavoproteins might well be classified as 

 reduced pyridine nucleotide dehydrogenases. It is worth noting that 

 the electron acceptor is now firmly attached to a protein molecule 

 as in the case of the cytochromes. The pyridine nucleotides thus 

 occupy a unique position as electron acceptors in that they exist 

 largely in the free state. This fact undoubtedly enables them to play 

 their important role in anaerobic oxidation-reduction reactions. 



The flavoproteins reduced by the pyridine nucleotide must now 

 in turn be oxidized. This can be accomplished by methylene blue 

 in the case of the isolated systems. In the intact cell, however, this 

 cannot be the pathway. The direct oxidation of flavoproteins by 



