THE FOLIC ACID GROUP 591 



ration from whey. 145 2-Amino-4-hydroxy-6-formylpteridine is also an 

 effective inhibitor of xanthine oxidase and related enzymes. 146 



Pyrimidine Derivatives. The toxicity of either 2,4-diamino-6,7-di- 

 methylpteridine or 2,6-diaminopurine for Lactobacillus casei is reported 

 to be prevented in a competitive manner by either folic acid or purines 

 under highly specific conditions, particularly with concentrations of folic 

 acid which limit growth. 147 The reversal of the toxicity of the pteridine 

 occurs over a relatively restricted range with purines, whereas the reversal 

 by folic acid can be accomplished over a wide range of concentration of 

 inhibitor. 147 This indicates that the effect of the purines on the inhibited 

 system is probably indirect. The reversal of the toxicity of 2,6-diamino- 

 purine differs from the usual purine effect in that adenine prevents the 

 toxicity over a much greater range of concentrations than does folic 

 acid. 147 This suggests the possibility that the folic acid effect is indirect, 

 presumably in eliciting synthesis of adenine, which in turn competes with 

 the diaminopurine. The possibility exists, however, that a single com- 

 pound, such as 2,6-diaminopurine, may effectively inhibit the utilization 

 of two different metabolites. 2-Amino-4-hydroxypteridine derivatives, 

 2-aminopurine, 2-amino- and 2,4-diamino-6,7-dihydroxypteridines simi- 

 larly produce inhibitions of Lactobacillus casei stimulated by folic acid; 

 these inhibitions are prevented by purines. These compounds, however, 

 do not inhibit growth of Lactobacillus casei in the presence of thymine 

 and purines, 'this contrasts to 2,4-diamino-6,7-dimethylpteridine, which 

 inhibits growth of the organism under either condition. 147 2,4-Diamino- 

 5-methyl- and 5,6-dimethylpyrimidines are intermediate in their behavior 

 toward reversal with purines and folic acid. 147 Growth of Lactobacillus 

 casei stimulated by either thymine or folic acid is inhibited by 5-nitro- 

 uracil; 148 ' 149 however, the toxicity of 5-nitrouracil is prevented by uracil 

 under conditions in which folic acid exerts no effect. 150 



Miscellaneous 



Miscellaneous analogues of folic acid which have been found to exert 

 inhibitory effects on the utilization of folic acid by some organisms are 

 indicated in Table 22. 



4-Desoxy folic Acid is reported to decrease the apparent folic acid con- 

 tent of the liver and produce both anemia and leucopenia in rats on a 

 diet supplemented with succinylsulfathiazole. 133 



N-\N -( 2-Amino-/ + ,6-dihydroxypteridine-7 ' -carboxylyl) -p-aminoben- 

 zoyl]--L-glutamic acid is isomeric with 7-hydroxy-9-oxofolic acid (Table 

 19) and is less than half as effective in inhibiting the growth of Lacto- 

 bacillus casei as is the isomer resembling folic acid. 125 



Quinoxaline has a slight inhibitory effect on the growth of Streptococcus 



