138 PTEROYLGLUTAMIC ACID 



bon of serine. Conversely PGA deficiency reduces Ihc utilization of /i-carljon 

 of serine and to a smaller extent that of the a-carbon of glycine. These re- 

 lationships are expressed schematically in Fig. 9. 



The in vitro incoiporation of glycine, containing C'^ in the carboxyl posi- 

 tion, by chick liver liomogenates is decreased in PGA deficiency (Totter 

 et al^*^). This effect was observed both in the Hver proteins and the phospho- 

 hpid fractions and was not influenced by in vitro addition of PGA to the 

 deficient liver homogenates. 



Elwyn and Sprinson''^ found that the methyl group of thymine is derived 

 from the a-carbon of glycine and the jS-carbon of serine. This indicates 

 that the methyl carbon of thymine is derived from a one-carbon intermedi- 

 ate by methylation of a pyrimidine nucleus. 



h. Counteraction of Glycine Toxicity by PGA 



Feeding large amounts of glycine depresses the growth of chicks and rats. 

 The growth depression induced by 10 % glycine in rats can be prevented by 



H2N-CH2-COOH 



B12 



HO NH, 



HCOOH '^^^ H^C-CH.-COOH 



Fig. 9. Effect of B12 and PGA on conversion of glycine and serine to "formate 

 pool." 



supplementation with PGA whereas a liver extract containing vitamin B12 

 is ineffective (Dinning et al^^). Similarly Machlin et aZ.^^ found that 6% 

 glycine depresses the growth of chicks and that additional quantities of 

 PGA prevent the growth depression. It is thus apparent that the PGA re- 

 quirements are increased by high levels of glycine. 



c. Effect on Purine Synthesis in Animals 



Drysdale et aZ.^" studied the effect of PGA depletion in rats on the in- 

 corporation of formate into purines. The rats were rendered deficient in 

 PGA by maintenance on a sulfasuxidine-containing diet until they exhibited 

 symptoms of leucopenia. The control animals were given PGA for 4 days, 

 which induced a remission of the leucopenia. This procedure of depleting 



^8 J. R. Totter, B. Kelley, P. L. Day, and R. R. Edwards, Federation Proc. 9, 238 



(1950). 

 " D. Elwyn and D. B. Sprinson, J. Am. Chein. Soc. 72, 3317 (1950). 

 « J. S. Dinning, C. K. Keith, P. L. Day, and J. R. Totter, Proc. Soc. Exptl. Biol. 



Med. 72, 262 (1949). 

 ■"9 L. J. Machlin, C. A. Denton, and H. R. Bird, Federation Proc. 10, 388 (1951). 

 ^0 G. R. Drysdale, G. W. E. Plant, and H. A. Lardy, ./. Biol. Chem. 193, 533 (1951). 



