574 THE BIOCHEMISTRY OF B VITAMINS 



with xanthopterin increases the production of microbiologically active 

 forms of folic acid. 75 



The leucopenia and anemia in rats resulting from the action of sulfa- 

 thiazole is reported to be alleviated by xanthopterin, folic acid, or a sub- 

 stance termed vitamin Bi 4 , which increases cell proliferation in a beef 

 bone marrow suspension but inhibits proliferation of a suspension of 

 Brown Pearce rabbit tumor cells. 102 Vitamin B i4 , isolated from human 

 urine, is much more effective than xanthopterin ; yet the activity of both 

 xanthopterin and folic acid is reportedly increased by incubation with 

 xanthine oxidase from milk, or with gastric mucosa of rats. 2-Amino-4- 

 hydroxy-7-methylpteridine counteracts the effects of both xanthopterin 

 and vitamin B 14 . 102 > 103 



Since xanthopterin is inactive in treatment of pernicious anemia 95 

 and does not replace folic acid for chicks, 104, 105 the relationship between 

 xanthopterin and folic acid in the rat is somewhat obscure. The possibility 

 that this and related pterins may prevent the metabolism and loss of folic 

 acid in enzymatic reactions not involved in hemapoiesis and growth must 

 also be considered. This is further emphasized by the ability of a number 

 of pterins and related substances to exert a beneficial action in chicks on 

 a folic acid-deficient diet. Thus, fed at 20 mg per 100 g diet over a four 

 week period the following compounds gave on occasion what appeared to 

 be significant growth stimulation of chicks: 105 2,4-dihydroxy-6,7-dicar- 

 boxypteridine, 2-mercapto-4-hydroxy-7-carboxypteridine, 2-amino-4- 

 hydroxy-7-carboxypteridine, 2-amino-4,6-dihydroxy-7-carboxypteridine, 

 2,4-dihydroxy-6-(or 7)-hydroxy-7(or 6) -carboxymethylpteridine, 2-ami- 

 no-4-hydroxy-6 (or 7)-hydroxy-7(or 6) -methylpteridine, 2,4-dihydroxy-6 

 (or 7)-hydroxy-7(or 6) -methylpteridine, bisalloxazine, 6-amino-2,4,8-tri- 

 hydroxypyrimido(4,5-e)pteridine, 2,6-dihydroxy-4,5-diaminopyrimidine, 

 and alloxan under conditions of suboptimal concentrations of folic acid. 

 Of these compounds, only 2-amino-4-hydroxy-7-carboxypteridine and 

 2-mercapto-4-hydroxy-6,7-dicarboxypteridine under similar conditions 

 stimulated hemoglobin formation. 2,4-Diamino-6,7-dicarboxypteridine, 

 2,4-diamino-7-carboxypteridine, 2,4-dihydroxy-7-carboxypteridine, and 

 2-mercapto-4-hydroxy-7-carboxypteridine were also found to stimulate, 

 under certain conditions, hemoglobin formation in chicks on suboptimal 

 concentrations of folic acid. 105 The presence of folic acid in suboptimal 

 amounts is essential for the response of all these factors. 105 With 2-amino- 

 4-hydroxypteridine, 2,4-diaminopteridine, 2-amino-4-hydroxy-6,7-dicar- 

 boxypteridine, 2,4-diamino-6,7-dimethylpteridine, 2-amino-4-hydroxy-7- 

 methylpteridine, 2,4-diamino-7-methylpteridine, or 2,4-diamino-6,7- 

 diphenylpteridine, no stimulatory effects were noted on either growth or 

 hemoglobin formation. 105 



