FORMIC ACID AXD FORMATE METABOLISM 285 



d. Formate as a Source of the Labile Methyl Group (Reactions 6 and 

 8). Sakami and Welch^" reported, on the basis of in vitro tests with li\-er 

 slices, that the rat is able to synthesize the labile methyl group of methio- 

 nine or of cholme from C'Mormate. This was the first demonstrated 

 that this important radicle can be synthesized in the hver; it was pre- 

 viously believed to be available only from dietary sources, and from intesti- 

 nal synthesis. Folic acid apparently plays as important a role in the syn- 

 thesis of these labile methyl groups as it does in other syntheses. For 

 example, hver slices from rats deficient in folic acid converted less C^*- 

 formate to methionine-methyl than did slices from the livers of rats which 

 had received PGA shortly before the rat was sacrificed. Moreover, an 

 appreciably lower amomit of C^^-formate was mcorporated mto the choline- 

 methyl when it was fed to folic acid-deficient rats than when it was given 

 to animals ha\Tng an adequate amount of this vitamin. ^^^ The conversion 

 of formate to labile methyl groups has been repeatedly confirmed both in 

 vitro and in vivo.^^^-""^^ It was shown to occur in germ-free rats.^*^'^®^ 

 Both formaldehyde 1^^ and methanoP^^- 1^2,193 gerve as precursors, but bi- 

 carbonate does not.i^^'i^«'i8^ Du Vigneaud et aU^'' noted that 69 to 75% of 

 the deuterium was lost in the syTithesis of choline methyl from doubly labeled 

 methanol, Ci''D30H. This is consistent with the hypothesis that formic 

 acid is an intermediate. 



Stekol et al.^^^ reported that \atamin B12 increased the choline synthesis 

 from formate, while Verly and associates, ^^' as well as Arnstein and Neu- 



"8 W. Sakami and A. D. Welch, /. Biol. Chem., 187, 379-384 (1950). 

 179 J. A. Stekol, S. Weiss, and K. Weiss, Ahst. Am. Chem. Soc, 120th Meeting (New 

 York, N. Y., Sept. 1951), 21 C. 



18° P. Siekevitz and D. M. Greenberg, /. Biol. Chem., 186, 275-286 (1950). 



181 S. Jonsson and W. A. Mosher, /. Am. Chem. Soc, 72, 3316 (1950). 



182 P. Berg, /. Biol. Chem., 190, 31-38 (1951). 



183 S. Kiikwood and L. Marion, Can. J. Chem., 29, 30-36 (1951). 



18" V. du Vigneaud, W. G. Verly, and J. E. Wilson, /. Am. Chem. Soc, 72, 2819-2820 

 (1950). 



185 H. G. Wood, Harvey Lectures, 45, 127-148 (1949-1950). 



186 V. du Vigneaud, C. Ressler, and J. R. Rachele, Science, 112, 267-271 (1950). 



187 V. du Vigneaud, W. G. L. Verlv, J. E. Wilson, J. R. Rachele, C. Ressler, and J. M. 

 Kinnev, /. Am. Chem. Soc, 73, 2782-2785 (1951). 



188 C. Mitoma and D. M. Greenberg, Federation Proc, 10, 225 (1951). 



189 W. G. L. Verly and V. du Vigneaud, /. Am. Chem. Soc, 72, 2819-2820 (1950). 

 IS" C. Ressler, J. R. Rachele, and V. du Vigneaud, J. Biol. Chem., 197, 1-5 (1952). 

 "1 V. du Vigneaud, C. Ressler, J. R. Rachele, J. A. Reyniers, and T. D. Luckey, J. 



Nutrition, 45, 361-376 (1951). 



1" V. du Vigneaud and W. G. Verly, /. Am. Chem. Soc, 72, 1049 (1950). 



1" W. G. Verly, J. E. Wilson, J. AI. Kinney, and J. R. Rachele, Federation Proc, 10, 

 264(1951). 



19" J. A. Stekol, K. W. Weiss, and S. Weiss, Federation Proc, 10, 252 (1951). 



