ANALOGS OF RIBOFRAVIN AND FAD 

 Diaminouracil 



6,7-dimethyl-8-fo-l'-ribityl)-lumazine 



535 



Riboflavin 



(3) 



lumichrome + ribito' 



riboflavin- 5 '-P + AMP 



(1) 



r 



riboflavin- 5 '-P 



(4) 



^ riboflavin + P 



(1) flavo kinase 



(2) FAD pyrophosphorylase 



(3) riboflavinase 



(4) phosphomonoesterase 



(5) nucleotide pyrophosphatase 



(Reaction (6) represents a possible formation of FAD directly from riboflavin and 

 ATP, as postulated by Masuda (1955) in E. ashbyii; reactions (1) and (2) also require 

 ATP) 



Many analogs, in which various parts of the riboflavin or FAD structure 

 have been modified, have been examined and very few are able to replace 

 riboflavin, possibly due both to inability to form the coenzyme analogs and 

 to relative inactivity of the coenzyme analogs when formed. Most of these 

 analogs are not significantly inhibitory to riboflavin function, indicating 

 the high degree of specificity in these reactions. Beinert (1960) has classified 

 the structural modifications producing most of the interesting analogs into 

 those where (1) the riboflavin is altered (as by replacement of ribitol by 

 other sugar alcohols or alkyl groups, replacement of the isoalloxazine ring 

 by other ring systems, or substitutions in the isoalloxazine ring), (2) ribo- 

 flavin esters other than the 5'-phosphate are synthesized (as the diphos- 

 phate, acetylphosphate, or sulfate), and (3) dinucleotides of riboflavin 

 have the AMP replaced by other nucleotides (such as GMP, IMP, CMP, 

 or UMP). 



In this chapter we shall be concerned with the rather simple and obvious 

 analogs of riboflavin and FAD. There are several types of drug and me- 

 tabolic inhibitor that probably interfere in one way or another with ri- 

 boflavin metabolism or function — such as the promazines, the antibiotic 

 tetracyclines, the acridine antiseptics, certain antimalarials, and perhaps 

 some of the chelators of the phenanthroline and bipyridine types — and 

 these will be discussed for the most part in future chapters. Quinacrine 

 only will be treated in some detail at the end of this section because it is 

 the best studied riboflavin analog. 



