146 



THE BIOCHEMISTRY OF B VITAMINS 



than there is for the nicotinic acid enzyme systems, e.g., a fiavoprotein 

 which is reduced by a particular substrate can be reoxidized only by cer- 

 tain specific substances, whereas a pyridine nucleotide reduced by one 

 metabolic system can be reoxidized by any of a number of other metabolic 

 systems; (3) many of the reactions catalyzed by the phosphopyridine 

 coenzymes are those in which the potentials of the reacting systems ap- 

 proximate those of the coenzymes, and hence the reactions may proceed 

 in either direction. The redox potential of riboflavin, however, is inter- 

 mediate between the low values of most organic metabolite systems (and 

 the nicotinic acid coenzymes) and the high values of the cytochrome 

 systems or oxygen itself. The differences are of sufficient magnitude that 

 most reactions catalyzed by flavoproteins may proceed effectively in one 

 direction only. Consequently, reversal of the direction in which a reaction 

 catalyzed by a fiavoprotein proceeds is seldom encountered, and it has 

 become customary to specify one system as the hydrogen donor and the 

 other as the hydrogen acceptor, rather than to treat them in general 

 terms of coupled systems. 



When the coenzymes of riboflavin are alternately reduced and oxidized 

 it is believed to be by a process in which the hydrogen atoms are accepted 

 or donated one at a time. This mechanism is possible since the flavin 

 nucleus can exist in an intermediate state of reduction in which a stabi- 

 lized semiquinoid radical is formed — a process which can be observed 

 experimentally. 62 The predominant structures among the various resonance 

 forms of the coenzymes are indicated as : 



H 3 C- 



H 3 C- 



N N 



A/ \/ \ 



^W 



c 



NH 



+H 



stabilized +H 



semiquinoid ^. "*• 



radical — H 



H 3 C- 



H 3 C- 



R 



I H 



N N 



vv v \ 



H || 

 O 



c 



NH 



Reactions Catalyzed by Flavoproteins. For discussion, the reactions 

 catalyzed by flavoproteins may be classified in two groups: (1) those in 

 which the enzyme reacts directly with the primary substrate being metab- 

 olized, and (2) those in which the pigment is a secondary acceptor of 

 the hydrogen atoms. The substrates with which the flavoproteins have 

 been shown to react directly are D-amino acids, L-amino acids, glycine, 

 L-hydroxy acids, aldehydes, purines, and substances not ordinarily en- 

 countered under natural conditions, such as quinine and reduced dyes. 

 In the other group of reactions, the fiavoprotein reacts with an "inter- 

 mediate carrier," which is either one of the two dihydropyridine nucleo- 



