IV. lUoniKIMIf'AL SYSTKMS 187 



which reihicos Ihc iiocd t'oi- mass action pressure of large anioimls of caiixni 

 dioxide. 



Serine synthesis in the rat from isotopic formate is decreased in IHIA 

 deficiency."" 



PGA has been similarly shown to l)e imolved in methionine synthesis 

 from homocystine in animals,'- and methionine synthesis in yeast can he 

 inhibited by 4-aminopteroylgliitamic acid and the action of the antagonist 

 reversed by the citrovorum factor."*^ 



C). PCJA i\ Sixgle-Carbon Transfer in Animals 



Pteroylglutamic acid has been shown to be involved in the synthesis of 

 serine, the conversion of serine to glycine, the synthesis of methionine, and 

 the synthesis of purines in the rat. Both vitamin B12 and PGA are concerned 

 in the synthesis of choline and methionine. 



a. Serine-Glycine Relationships 



Incorporation of radioactive formate into serine is greatly depressed in 

 PGA deficiency induced by sulfonamide feeding (Plant et al^^). Treatment 

 with PGA for 4 days prior to formate administration increases C''' fixation 

 into liver protein tenfold. Serine synthesis is most markedly affected; 

 glutamic acid, arginine, and glycine are less affected. The carbon of formate 

 was predominantly incorporated into the jS-carbon of serine. 



Heme from the blood of PGA-treated rats also contains an appreciable 

 quantity of C'^, whereas that from deficient rats contains none. Biotin 

 deficiency has no influence on incorporation of C^"* from formate into 

 iS-carbon of serine, showing that this effect of PGA deficiency is a specific 

 one and is not the result of a general manifestation of vitamin deficiency 

 such as inanition. 



Pteroylglutamic acid is also concerned in the conversion of serine to 

 glycine for hippuric acid synthesis in the rat (Elwyn and Sprinson''^). From 

 the lower utilization of serine and the greater utilization of glj^cine in the 

 PGA-deficient rat, it has been estimated that the rate of conversion of 

 serine to glj'-cine is reduced to one-sixth of the normal value in PGA defi- 

 ciency. 



A comparison has also been made of the rates of incorporation of a-carbon 

 of glycine and /3-carbon of serine into choline.^^ B12 is concerned mainly 

 with the utilization of a-carbon of glycine but not the utilization of /3-car- 



" G. W. E. Plaut, J. J. Betheil, and H. A. Lardy, J. Biol. Chem. 184, 795 (1950). 



« J. S. Dinning, C. K. Keith, and P. L. Day, J. Biol. Chem. 189, 515 (1951). 



" H. P. Broquist, Federation Proc. 11, 191 (1952). 



*' D. Elw^n and D. B. Sprinson, J. Biol. Chem. 184, 475 (1950). 



" J. A. Stekol, S. Weiss, and K. W. Weiss, Arch. Biochem. and Biophtjs. 36, 5 (1952). 



