174 PTEROYLGLUTAMIC ACID 



Riboflavin deficiency also produced hematological changes resembhng 

 those of PGA insufficiency. The leucopenia but not the anemia could in 

 some cases be corrected by administration of PGA, or by riboflavin, or by 

 a combination of both.^^ Restriction of intake of a diet containing riboflavin 

 also produced the typical blood dyscrasia which suggests that limitation of 

 other dietary essentials by low feed consumption may be an important fac- 

 tor. 



Severe granulocytopenia and anemia were produced in rats fed protein- 

 free diets. ^® The condition was prevented by casein alone but not by PGA. 

 The blood dyscrasia could not be cured by either casein or pteroylglutamic 

 acid alone but did respond to a combination of the two. When weanhng 

 rats were given a 4 % casein diet, the animals again became anemic, leuco- 

 penic, and granulocytopenic. In this case the leucocyte count was increased 

 by PGA alone or by parenteral 15-unit liver extract. The activity of the 

 hver extract could not be accounted for on the basis of its PGA content as 

 determined by microbiological assay. The simultaneous administration of 

 methionine and threonine with the PGA increased the incidence and magni- 

 tude of the response. This observation foreshadowed subsequent work which 

 established the role of PGA in the metabolism of these compounds. 



The interchangeability of pteroylglutamic acid and liver extract in cor- 

 recting the agranulocytosis has been confirmed both on a normal and on a 

 low protein diet.^^ In these experiments it was impossible to account for 

 the activity of the liver extract on the basis of PGA or its conjugates as 

 measured by microbiological assay after enzymatic hydrolysis. 



Anemia, leucopenia, and hemorrhage and necrosis of the adrenals were 

 observed by Daft et al. in rats fed thiourea in a purified diet.^^ The blood 

 dyscrasia was not prevented by thyroid powder or thyroxine but was cor- 

 rected by administration of PGA. These results are in contrast to the re- 

 ported ineffectiveness of PGA in preventing the appearance of agranu- 

 locytosis in two patients receiving thiouracil.-*^ Higgins-^ observed that 

 pteroylglutamic acid at a level of 18 7 per day counteracted the hypo- 

 chromic anemia induced by feeding of promin and promizole to young rats 

 on a purified diet. 



c. PGA and Reproduction in the Rat 



Reproduction performance in rats during lactation is improved by the 

 addition of PGA to a purified diet. The maximum improvement is obtained 

 when the supplement is given to the parent animals from the time of wean- 



18 C. W. Mushett and G. A. Emerson, Federation Pvoc. 7, 295 (1948). 



19 F. S. Daft, A. Romberg, L. L. Ashburn, and W. H. Sebrell, Proc. Soc. Exptl. Biol. 

 Med. 61, 154 (1946). 



20 E. V. Newman and B. F. Jones, /. Am. Med. Assoc. 132, 77 (1946). 



21 G. M. Higgins, Proc. Staff Meetings Mayo Clinic 19, 329 (1944). 



