The Flavoproteins 



T. R. HOGNESS 



University of Chicago 



r-|-iHE flavoproteins constitute a relatively large class of the 

 _L respiratory enzymes. As we know them today they are charac- 

 terized by having as prosthetic groups either alloxazine mono- 

 nucleotide, i.e., riboflavin phosphate, or alloxazine adenine 

 dinucleotide, which is composed of both riboflavin phosphate and 

 adenylic acid. They are further characterized by their reactivity 

 toward oxygen— some to a very limited extent— when in the re- 

 duced form. Many of them are oxidized by methylene blue; one is 

 oxidized by fumaric acid; and one is specifically oxidized by a 

 known member of the hydrogen transport system: the flavoprotein 

 cytochrome c reductase, in its reduced state, is oxidized by cyto- 

 chrome c. 



In the oxidized state the flavoproteins as a group can be reduced 

 by a variety of substrates— dihydrotriphosphopyridine nucleotide 

 (cozymase II), dihydrodiphosphopyridine nucleotide (cozymase I), 

 the d!-amino acids, xanthine and other purines, and some of the 

 aldehydes. Each particular flavoprotein, however, is specific toward 

 one (or one class) of the above substrates. The chemical structures 

 of both alloxazine mononucleotide and alloxazine adenine dinucleo- 

 tide are depicted in Figures 1 and 2. 



Stern and Holiday (1), by spectrographic methods, first found 

 that the prosthetic group of Warburg's old yellow enzyme (2), 

 which will be considered in more detail below, was a derivative 

 of alloxazine, and the structure of the riboflavin phosphate was 

 finally deteiTnined independently by Kuhn (3), Karrer (4), and their 

 collaborators. Theorell (5) demonstrated that the enzyme contained 

 one molecule of phosphate; and later Kuhn, Rudy, and Weygand (6), 

 by synthesizing riboflavin-5-phosphoric acid, demonstrated the posi- 

 tion occupied by the phosphate group. 



In Figure 1 the hydrogenation of the alloxazine mononucleotide is 

 also indicated. The process of hydrogenation undoubtedly takes 

 place in such a way that one hydrogen atom at a time is transferred 

 from the substrate molecule to the riboflavin phosphate. The forma- 

 tion of a red-colored intermediate in the reduction process consti- 

 tutes much of the evidence in favor of this view. Kuhn and Wagner- 



134 



