590 THE BIOCHEMISTRY OF B VITAMINS 



benzoic acid and folic acid prevent the toxicity to a certain extent, but do 

 not prevent the toxicity of concentrations of 3 y per cc or greater. This 

 type of phenomenon is characteristic of the corresponding 4-amino 

 analogues of folic acid for a number of organisms. However, it is interest- 

 ing that the substituted pteridine inhibits the system of enzymes related 

 to folic acid in an organism which synthesizes the vitamin. Most folic 

 acid analogues are not able to prevent effectively the utilization of this 

 vitamin group in organisms which synthesize the vitamin. 



Some of the 2,4-diaminopteridines act synergistically with sulfonamides 

 in preventing growth of Escherichia coli, Staphylococcus aureus and Lacto- 

 bacillus casei. li4i For example, a minimum of either 1500 y per 10 cc of 

 2,4-diamino-6,7-dimethylpteridine or 1000 y per 10 cc of sulfathiazole is 

 necessary to prevent the growth of Staphylococcus aureus, but a combina- 

 tion of 20 y per 10 cc of each of the two compounds allows approximately 

 the same degree of inhibition. Similarly, a minimum of either 2000 y per 

 10 cc of the same pteridine or 50 y per 10 cc of sulfathiazole prevents 

 the growth of Escherichia coli, but a mixture of 100 y per 10 cc of the 

 pteridine and 20 y per 10 cc of sulfathiazole prevents growth of the 

 organism. 2,4-Diamino-6,7-diphenylpteridine, at a concentration which is 

 ineffective alone, will reduce more than ten-fold the amount of sulfa- 

 thiazole necessary for inhibition of growth of Lactobacillus arabinosus. 

 These results indicate that two biological processes in sequence are 

 inhibited. 144 



Although 2,4-diamino-6,7-diphenylpteridine does not affect growth or 

 hemoglobin formation in chicks, 105 it is reported to affect blood formation, 

 particularly leucocytes in rats. 133 The pteridine appears to cause a decrease 

 of folic acid in the liver of chicks, 105 but no decrease in the folic acid 

 content of the liver is noted for rats. 133 Other pterins tested with rats 

 included 2,4-diamino-6,7-dimethylpteridine, 2,4-diamino-6,7-di (4-amino- 

 phenyl) pteridine and 2-amino-4-hydroxy-6,7-diphenylpteridine. 133 



In chicks, both 2-amino-4-hydroxy-6,7-dimethylpteridine and 2-amino- 

 4-hydroxy-6,7-diphenylpteridine (20 mg per 100 g of diet containing 15 y 

 of folic acid) inhibit growth of chicks and decrease hemoglobin formation. 

 The inhibitory effect is prevented by folic acid at 60 y per 100 g of diet. 105 

 2-Amino-4-hydroxy-6(or 7)-hydroxy-7(or 6) -methylpteridine appears to 

 inhibit hemoglobin formation, but stimulates growth of chicks on a 

 diet containing suboptimal concentrations of folic acid. 2,4-Dihydroxy- 

 benzo(e) pteridine was slightly inhibitory to both growth and hemoglobin 

 formation, whereas 2,4,6-trihydroxy-7-carboxypteridine was inhibitory 

 only to hemoglobin formation. 105 It is interesting that 2-amino-4- 

 hydroxypteridine-7-carboxylic acid and related pteridines prevent the 

 oxidation of either xanthopterin or xanthine by a xanthine oxidase prepa- 



