140 PTEROYLGLUTAMIC ACID 



by isotope studies that adult rats cannot utilize free thymine for nucleic 

 acid synthesis. ^^ 



Pigs, however, have been observed to give a hematological response to 

 thymine in doses of 10 g. daily (Welch and Heinle^*). 



Of special interest is the fact that patients with pernicious anemia respond 

 hematologically to thymine, uracil, and thymidine. Spies et al}^ found that 

 15 g. of thymine is capal)le of producing a hematological response similar to 

 that induced by PGA. About five thousand times as much thymine as PGA 

 is required. This ratio is similar to the relative effectiveness of these two 

 compounds in promoting the growth of S. faecalis (Stokes^). In view of the 

 ineffectiveness of uracil in replacing thymine in the nutrition of PGA- 

 requiring organisms, the observations of Vilter d al}^ that uracil in doses 

 of 15 to 30 g. per day often causes hematological remission are of special 

 interest. Quite surprising also is the fact that thymine proved effective in a 

 pernicious anemia patient who had become refractory to PGA. 



Thymidine, which is able to substitute for vitamin B12 in the nutrition 

 of certain lactic acid bacteria, has been reported by Hausmann" to be 

 effective in total doses of 2.0 and 2.8 g., respectively, and to produce a 

 response comparable to that elicited by PGA or vitamin B12 in pernicious 

 anemia. 



e. Influence of PGA and Vitamin Bn on Methionine and Choline Synthesis 



Both vitamin B12 and PGA have been shown to have a role in choline 

 and methionine metabolism in chicks and rats. This was first shown by the 

 work of Bennett, ^^ who found that rats with a certain previous dietary 

 history were able to utilize homocystine for growth in the absence of labile 

 methyl donors when supplemented with PGA and with purified liver extract 

 containing vitamin B12 . This requirement for PGA was observed both in 

 the absence and presence of sulfasuxidine. Since rats normally do not de- 

 velop PGA deficiency on a purified type 01 diet unless supplemented with 

 sulfonamide, the results of Bennett suggest that the PGA requirements of 

 the rat are increased on a "labile methyl"-deficient diet. Both vitamin B12 

 and PGA are required for synthesis of methionine from homocystine under 

 this regimen. 



On a methionine-deficient diet (containing alcohol-extracted peanut meal 



" A. A. Plentl and R. Schoenheimer, /. Biol. Chem. 153, 203 (1944). 



" A. D. Welch and R. W. Heinle, Pharmacol. Revs. 3, 345 (1951). 



85 T. D. Spies, W. B. Frommeyer, Jr., C. F. Vilter, and A. English, Blood 1, 185 



(1946). 

 56 R. W. Vilter, D. Horrigan, J. F. Mueller, T. Jarrokl, C. F. Vilter, V. R. Hawkins, 



and A. Seaman, Blood 5, 695 (1950). 

 " K. Hausmann, Lancet I, 329 (1951). 

 58 M. A. Bennett, Science 110, 589 (1949). 



