540 2. ANALOGS OF ENZYME REACTION COMPONENTS 



show a 70-75% depression of liver mitochondrial flavin, and dietary ribo- 

 flavin restriction also reduced the level (Beyer et al., 1961). The evidence 

 from depression of enzyme activity will be discussed later. The thorough 

 analysis of the effects of riboflavin deficiency on rats by Burch et al. (1956) 

 has shown that various tissues differ markedly in ability to retain FMN 

 and FAD (see accompanying tabulation). Deficiency of 23-day duration 



has little effect on brain flavins while liver levels drop rapidly. No necessary 

 correlation between total FMN or FAD and enzyme activity is evident, 

 indicating that some enzymes will lose their FMN or FAD much more 

 readily than others and that a fraction of the cellular flavin may be nonen- 

 zymically bound. On the basis of these results, one might expect riboflavin 

 analogs, when active, to exert differential effects on the various flavoen- 

 zymes, and it is likely that analyses for total flavins will not provide me- 

 tabolically significant figures. 



Effects on Flavoenzymes 



The enzymes most commonly used to test the inhibitory activity of 

 riboflavin analogs are those with dissociable flavin coenzymes, such as the 

 old yellow enzyme and D-amino acid oxidase, and in such cases an inhibi- 

 tion of a competitive nature is not unexpected. However, there are many 

 instances of the inhibition of enzymes which have very tightly bound co- 

 enzymes and these are more difficult to interpret. Some inhibitions of both 

 types are shown in Table 2-33. Inhibitions by riboflavin, FMN, and FAD 

 are also included because these show that it is not alwaj^s necessary to 

 consider inhibition as resulting from structural analogs. 



Most of these inhibitions appear to be noncompetitive. Thus the inhibi- 

 tions of L-galactono-y-lactone dehydrogenase by riboflavin, L-amino acid 

 oxidase by riboflavin and its analogs, and D-amino acid oxidase by ribo- 

 flavin are not reduced by increasing concentrations of FMN or FAD. How- 

 ever, the inhibitions of kidney D-amino acid oxidase by FMN and ribo- 

 flavin-5' -sulfate are competitive with respect to FAD, and the inhibition 



