188 PTEROYLGLUTAMIC ACID 



In confirmation with observations previously made by these same work- 

 ers/^ on a sulfasuxidine diet the severity of the anemia was greater on a 10 % 

 casein diet than on a 26 % casein diet even when the "x methyl PGA" was 

 present in the ration. 



The urinary excretion of tyrosyl derivatives (hydroxyphenol) was ab- 

 normal in the PGA-deficient pigs and was not altered by therapy with PGA 

 or liver extract. This is an interesting observation in view of the findings 

 that the failure of ascorbutic guinea pigs to metabolize tyrosyl compounds 

 can be corrected by administration of PGA.^° 



Heinle et al}^ have found that pigs made deficient on a diet containing 

 sulfasuxidine and "x methyl PGA" respond well to PGA initially, but as 

 the deficiency is maintained the ability to respond diminishes. At this point 

 purified liver extract gives a response. Conversely, they also observed that 

 when a pig kept on this PGA-deficient diet for several months was given 

 large amounts of liver extract and later vitamin B12 , there was an initial 

 partial response. The blood values were maintained at an improved level 

 but never at a normal level. Very marked macrocytosis developed and per- 

 sisted, but was promptly corrected by administration of PGA. A vitamin 

 B12 deficiency was produced by feeding a diet containing purified soybean 

 protein. On this regimen an anemia developed which was less macrocytic 

 than that observed in PGA deficiency and no megaloblasts were found in 

 the bone marrow. The animals responded to vitamin B12 therapy. 



Johnson et al.^^ studied the effects of PGA and vitamin B12 deficiency 

 in the baby pig using synthetic milk diets containing purified soybean pro- 

 tein. This protein is lower in vitamin B12 than casein and permitted the 

 simultaneous production of PGA and vitamin B12 deficiencies. When pigs 

 were placed on a 20 % protein diet without vitamin B12 or PGA and with 

 0.0% of sulfathalidine, the growth rate decreased and a mild anemia de- 

 veloped. After a 7-week depletion period, administration of vitamin B12 

 produced an increase in growth and a 7 % reticulocyte peak on the fifth 

 day. After 4 weeks of continued injection of 2 7 of vitamin B12 daily, the 

 oral administration of PGA produced a second sharp reticulocyte peak of 

 7 % on the second day. 



The pigs were also given a diet deficient in PGA and vitamin B12 but 

 without sulfathalidine for 3 weeks which was followed by the addition of 

 "x methyl PGA" for the next 2 weeks. At this point cither PGA or vitamin 

 B12 provoked the maximum hematological and bone marrow responses but 

 only B12 elicited a growth response. 



80 C. W. Woodruff, M. E. Cherririgton, A. K. Stockoll, and W. .1. Darby, J. Biol. 



Chem. 178, 861 (1949). 

 8' R. W. Heinle, A. D. Welch, and II. L. Shorr, ./. TaiI. Clin. Med. 34, 1703 (1949). 

 82 B. C. Johnson, A. L. Neumann, R. O. Nesheim, M. F. James, J. L. Krider, A. 8. 



Dana, and J. B. Thiersch, J. Lab. Clin. Med. 36, 537 (1950). 



