586 THE BIOCHEMISTRY OF B VITAMINS 



within ten days. 136 The effects of the analogues are similar to those in 

 other animals and include: hemorrhagic diarrhea, weight loss, leucopenia, 

 hemoconcentration and degeneration of the bone marrow. Erythropoiesis 

 and myelopoiesis are inhibited. Lymphopoiesis is less affected. 130 



Monkeys are susceptible to the inhibitory action of 4-amino-4-desoxy- 

 folic acid, in contrast to the effect of L-x-methylfolic acid. 116 



The characteristic growth response to estrogens of the genital tracts 

 of female chicks 137 and rats 137 and newly metamorphosed frogs 138 

 (Rana clamitans) is inhibited by 4-amino-4-desoxyfolic acid. The de- 

 crease in the response of the female frog oviducts to estradiol resulting 

 from administration of the amino analogue is not affected by supple- 

 mental folic acid even at 100 times (5 mg) the concentration of the 

 analogue (0.05 mg) . 138 High concentrations of folic acid in both the chick 

 and rat tend to prevent the effect of the analogue. 137 



4-Amino-4-desoxyfolic acid also prevents the development of larvae of 

 Drosophila melanogaster in a synthetic medium containing growing yeast. 

 Folic acid does not appear to prevent this inhibition. 117, 118 



The analogue also causes a marked erythrophagocytosis by granu- 

 locytes in human blood cell cultures. 121 



Marked effects of the 4-amino analogue on the blood islets in 6- to 

 8-day old chick embryos have been reported to be altered by folic acid, 

 but not by either refined liver extract or vitamin Bi 2 . 139 



Liver tissue from rats depleted of folic acid on a succinylsulfathiazole 

 diet has a decreased ability to oxidize tyrosine as compared with liver 

 tissue from normal animals. 139a The addition of folic acid in vitro par- 

 tially restores the ability to oxidize tyrosine, but neither liver extract 

 nor pteroylheptaglutamate has this effect. Liver tissue from rats fed 

 4-amino-4-desoxyfolic acid is similarly deficient in its ability to oxidize 

 tyrosine, but no effect on the system is obtained in vitro with folic acid, 

 vitamin Bi 2 , or liver extract. The administration of folic acid or refined 

 liver extract to the rat prevents the effects of the analogue on the ability 

 of the liver to oxidize tyrosine. The analogue does not inhibit the oxida- 

 tion of tyrosine by liver slices in vitro. 139 * 



4-Amino-4-desoxy-N 10 -methylfolic Acid [N-(4-Amino-4-desoxy-N 10 - meth- 

 ylpteroyl)-L-glutamic Acid]. In contrast to the effects of 4-amino-4- 

 desoxyfolic acid, the toxicity of 4-amino-4-desoxy-N 10 -methylfolic acid 

 for Streptococcus faecalis R is prevented competitively by folic acid, as 

 indicated in Table 20. 131 However, folic acid has little ability to prevent 

 the toxicity of the analogue for rats. 131 Animals receiving sub-lethal 

 amounts of 4-amino-4-desoxy-N 10 -methylfolic acid have normal growth; 

 and except for a little alopecia and occasional but never severe chromo- 

 dacryorrhea, anemia and leucopenia, the animals do not show symptoms 



