420 THE BIOCHEMISTRY OF B VITAMINS 



latter condition responds to removal of the parasite, to anti-pernicious 

 anemia liver extract, and stomach preparations, no report of vitamin 

 therapy being as yet available. 146 



It is thus apparent that a variety of common long recognized severe 

 afflictions must now be considered as avitaminoses, and that the symptoms 

 of these diseases generally respond well to both folic acid and vitamin 

 Bi 2 . It is equally apparent, however, that much work remains to be done 

 in elucidating the relationships of these B vitamins to the full measure 

 of the antipernicious effect of liver, and to erythrocyte maturation. There 

 are present indications that vitamin B i2 may function in the synthesis 

 of folic acid, and that folic acid functions in purine synthesis. 147 The 

 relationship of these observations to the etiology of the macrocytic 

 anemias remains for the present obscure, as do the relations of the other 

 B vitamins to these hematological symptoms. 148 



Deficiencies in Vertebrates other than Man. Folic acid deficiencies 

 have been produced in a number of lower animals, most notably 

 chicks, 149, 164 and monkeys. 150 In chicks the symptoms involve slow growth 

 and deficient feathering and a macrocytic anemia, and in monkeys, 

 diarrhea, gingivitis, and a macrocytic anemia. Folic acid is effective in 

 causing a remission in both cases. Folic acid deficiencies have been pro- 

 duced in mice by the use of the inhibitors, 1-methylfolic acid and 

 4-aminofolic acid (Chap. VD). 151 Typical deficiency has also been pro- 

 duced in rats. Both humans and rats develop severe blood dyscrasias 

 when treated with certain chemotherapeutic agents. In rats the agranulo- 

 cytosis and bone marrow hypoplasia produced in this manner (sulfa- 

 guanidine, sulfasuxidine) respond rapidly to folic acid administration. 

 Folic acid deficiency also apparently occurs in rats made deficient in 

 pantothenic acid (p. 423) , 152 and in some cases of blacktongue in 

 dogs 96,98 (p. 412), in which case the syndrome is more like canine sprue 

 than pellagra. Similar unclear relationships exist between folic acid and 

 the anemias resulting from riboflavin deficiency in rats, dogs, swine, and 

 monkeys. 153 - 154 Rats also have impaired lactation when folic acid-defi- 

 cient. 155 Folic acid is only partially effective in treating the blood changes 

 induced in rats by gastrectomy, 156 and thymine is ineffective in replacing 

 folic acid in the rat for either hematopoiesis or lactation, or in the chick 

 at all. 157 



OH 



N^S,X N ^OH 



HN=L N . 



xanthopterin 



