334 RIBOFLAVIN 



IV. Biochemical Systems 



M. K. HORWITT 



Knowledge of the close relationship between vitamins and biological oxi- 

 dations may be said to date from 1932, the year in which Warburg and 

 Christian^ discovered the first flavoprotein. This compound, often referred 

 to as the "old yellow enzyme," which they obtained from the aqueous ex- 

 tract of bottom yeast was soon separated^ into a protein and a yellow 

 prosthetic group. Stern and Hohday,^ using spectroscopic methods, found 

 that the prosthetic group of Warburg's yellow enzyme was a derivative of 

 alloxazine. This fact, when combined with the observations of Ellinger 

 and Koschara,^ Booher,* and Kuhn et al.^ on the correlations between vita- 

 min B2 and a water-soluble yellow-green fluorescent pigment, was soon 

 corroborated by the synthesis of riboflavin by the Kuhn^ • ^ and Karrer^ 

 schools. Theorell's'" demonstration that Warburg's enzyme contained one 

 molecule of phosphate and Kuhn, Rudy, and Weygand's^^ proof of consti- 

 tution of riboflavin-5-phosphoric acid were the concluding steps in a fasci- 

 nating story of the first separation, identification, and synthesis of the 

 prosthetic group of an enzyme. 



A. COENZYMES 



All flavoproteins can be characterized as specific proteins which contain 

 either flavin mononucleotide or flavin dinucleotide as prosthetic groups, or 

 coenzymes. The flavin mononucleotide, riboflavin phosphate, is not in the 

 strict sense a nucleotide, since the compound is derived from D-ribitol 

 rather than from D-ribose.^^ The location of the phosphoric acid at the 5 

 position has been definitely established. ^^ To date at least three flavopro- 

 teins with enzymatic activity have been shown to contain the mononucleo- 

 tide. These are Warburg's yellow enzyme, cytochrome c reductase, and 

 L-amino acid oxidase. 



Flavin adenine dinucleotide (FAD) is isoalloxazine adenine dinucleotide. 



1 O. Warburg and W. Christian, Biochem. Z. 254, 438 (1932). 



2 0. Warburg and W. Christian, Biochem. Z. 266, 377 (1933). 



3 K. G. Stern and E. R. Holiday, Ber. 67, 1104, 1442 (1934). 



4 P. Ellinger and W. Koschara, Ber. 66, 315, 808 (1933). 

 6 L. E. Booher, J. Biol. Chem. 102, 39 (1933). 



6 R. Kuhn, P. Gyorgy, and T. Wagner-Jauregg, Ber. 66, 317, 576, 1034 (1933). 

 ^ R. Kuhn, K. Reinemund, H. Kaltschmitt, R. Strobele, and H. Trischmann, Natur- 

 wissenschaften 23, 260 (1935). 



8 R. Kuhn, K. Reinemund, F. Weygand, and R. Strobele, Ber. 68, 1765 (1935). 



9 P. Karrer, K. Schopp, and F. Benz, Helv. Chim. Acta 18, 426 (1935). 

 10 H. Theorell, Biochem. Z. 272, 155 (1934). 



" R. Kuhn, H. Rudy, and F. Weygand, Ber. 69, 2034 (1936). 



'2 P. Karrer, P. Frei, and H. Meerwein, Helv. Chim. Acta 20, 70 (1037). 



