ANALOGS OF RIBOFLAVIN AND FAD 545 



cellaneous observations do not provide a satisfactory basis for understand- 

 ing the metabolic effects of riboflavin analogs. 



We have been discussing analogs of the riboflavin portion of FAD and 

 some mention of the adenine nucleotides as inhibitors should be made. The 

 D-amino acid oxidase of sheep kidney is inhibited competitively by various 

 purines and nucleotides (see accompanying tabulation) (Burton, 1951 a). 



It was shown that complexes between riboflavin and purines are formed 

 and have the following dissociation constants: caffeine 10 n\M, adenosine 

 30 mM, AMP 40 mM, ADP 37 mM, and ATP 39 mM. The formation of 

 such complexes might account for the enzyme inhibition in the case of 

 adenosine and caffeine, but cannot account for the more potent effects of 

 AMP and ADP, these latter substances competing with FAD for the apo- 

 enzyme site. The D-amino acid oxidase from pig kidney is likewise inhibited: 

 50% inhibition is given by 0.4-0.6 mM AMP, ADP, ATP, and IMP; by 

 6 mM adenine, adenosine, and hypoxanthine; and by 15-20 mM uracil, cyto- 

 sine, and ribose-5'-P (FAD 0.00014 mM in all cases) (Walaas and Walaas, 

 1956). The K, for the competitive 5'-AMP is 0.64 mM. Crandall (1959) 

 determined K^ for AMP as 0.1 mM for this enzyme. Flavokinase is inhi- 

 bited strongly by 5'- AMP {K^ = 0.025 mM), and it is possible that the 

 adenine portion of the nucleotide competes with the alloxazine ring of ribo- 

 flavin for the active center (Kearney, 1955). 



Quinacrine (Mepacrine, Atabrine, Atebrin) 



Quinacrine is an acridine derivative introduced by the Germans in 1932 

 for malaria therapy as a suppressive agent and is more effective than qui- 

 nine on the asexual forms of the plasmodia. Since the observation by Wright 

 and Sabine (1944) that FAD counteracts the inhibition of tissue respiration 

 by quinacrine, it has been commonly assumed that quinacrine exerts its 



