284 VI. ACETIC, FORMIC, AND PROPIONIC ACIDS 



acid rather than to fundamental differences in the mechanism of synthesis 

 of purines. One is forced to conclude that formate furnishes two carbons 

 for this molecule and that its incorporation in the molecule is related to the 

 function of CF. 



b. Thymine Synthesis (Reaction 3). Formate has been shown to be the 

 precursor of the methyl group in the pyrimidine, 5-methyluracil, or thymine, 

 in chicks, ^^^ as well as in rats.^''^ Thus, Elwyn and Sprinson^" found that 

 the C^* of L-serine-3-C^* and of glycine-2-C^'*, both of which are known 

 formate precursors, became incorporated in the CH3 group of thymine. 



c. Serine Synthesis (Reaction 5). Plant and associates"^ were the first 

 to demonstrate the fact that formate participates in the synthesis of serine; 

 it is incorporated in the /3-position (C-3). Thus, rats with a folic acid defi- 

 ciency utilized less formate for serine synthesis, and produced less C^^Oa, 

 than did pair-fed control rats which received folic acid. Moreover, it was 

 noted that biotm deficiency does not influence the synthesis; therefore, 

 folic acid deficiency specifically interferes with formate utilization. 



Sakami"* reported that when C^ ^-glycine and formate-C^^ were fed to 

 rats, serine as well as liver glycogen containing both C^' and C^* were 

 isolated from the liver hydrolysates. This reaction is pictured as follows : 



2H 



CH2(NH2)-Ci'OOH + HC»OOH > C"'H20H-CH(NH2)C"OOH > 



Ci^HjCO-Ci'OOH > Glycogen -C, C'^ 



The Transformation of Glycine and of Formate to Serine and to Glycogen i''* 



It has also been demonstrated that the formate used in the synthesis of 

 serme originates from glycine. "^''^^ It is postulated that the following 

 changes occur in the transformation of glycine to formate: 



O O 



II II 



NH2CH2-COOH > HCCOOH > HCOH CO2 



Glycine Glyoxylic Formic 



acid acid 



The Transformation of Glycine to Formate^'^ 



As early as 1946, Shemin"^ demonstrated by in vivo tests that the j8-carbon 

 of serine breaks down to yield glycine and formic acid. 



1" D. Elwyn and D. B. Sprinson, /. Am. Chem. Soc, 72, 3317-3318 (1950). 



1" G. W. E. Plant, J. J. Betheil, and H. A. Lardy, /. Biol. Chem., 184, 795-805(1950). 



"* W. Sakami, /. Biol. Chem., 176, 995-996 (1948). 



"5 W. Sakami, Federation Proc, 8, 246 (1949). 



"« P. Siekevitz, T. Winnick, and D. M. Greenberg, Federation Proc., 8, 250 (1949). 



i"D. Shemin, /. Biol. Chem., 162, 297-307 (1946). 



