84 CHOLINE 



Many observations support the view that foUc acid or a derivative in- 

 fluences formate metaboUsm in the rat and thereby affects the formation 

 of aminoethanol from serine and glycine and the formate-to-methyl syn- 

 thesis which may be involved in the conversion of aminoethanol to choline. 

 Totter et al. noted a favorable effect of folic acid on the metabolism of 

 glycine which was manifested by an increased excretion of porphyrins, be- 

 lieved to indicate improved synthesis of hemoglobin, and by a neutralization 

 of the symptoms of glycine deficiency produced by the administration of 

 sodium benzoate.^^^ Elwyn and Sprinson found that the conversion of N^^- 

 L-serine to glycine and the subsequent excretion of N^^-benzoylglycine were 

 reduced markedly in folic acid-deficient rats.^^- Stekol ei al. reported that 

 the deficiency impaired the use of the /3-carbon of serine and, to a lesser 

 extent, of the 7-carbon of glycine in choline formation.^^^' ^^^ The incorpora- 

 tion of C"-formate into serine of ]i\er proteins was greatly increased by the 

 treatment of deficient rats with folic acid,^^^ and the synthesis of the choline 

 methyl from methanol was improved by either folic acid or leucovorin.'^^- ^^^ 

 In confirmation of his own results^^*' ^^^ and of those of others,^™ Williams 

 found in in vitro studies that symptoms of folic acid deficiency in rats caused 

 by feeding the antagonist, aminopterin, included an inhibition of the liver 

 oxidases that convert choline and betaine aldehyde to betaine and of the 

 enzymes that methylate homocystine.^"^ In contrast to the slight influence 

 of a synthetic citrovorum factor, leucovorin, folic acid was necessary for 

 the optimal formation of N^-methylnicotinamide from administered nic- 

 otinamide in rats. ^''2 



As in the case of folic acid, B12 has been involved in both methyl and 

 formate metabolism. Oginsky found Bi2-deficient rats less able to form 

 methionine from homocystine and either choline or betaine.-"^ The de- 

 ficiency had no appreciable effect on the formation of choline methyl from 

 methanoP^® or from the |8-carbon of serine.^"* Arnstein and Neuberger,^''^ how- 



181 J. R. Totter, E. S. Amos, and C. K. Keith, J. Biol. Chem. 178, 847 (1949). 



192 D. Elwyn and D. B. Sprinson, J. Biol. Chem. 184, 475 (1950). 



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

 19^ J. A. Stekol, S. Weiss, B. Hsu, and P. Smith, Federation Proc. 11, 292 (1952). 



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



196 W. G. Verly, J. E. Wilson, J. M. Kinney, and J. R. Rachele, Federation Proc. 10, 

 264 (1951).' 



197 W. G. Verly, J. M. Kinney, and V. du Vigneaud, J. Biol. Chem. 196, 19 (1952). 



198 J. N. Williams, Jr., J. Biol. Chem. 191, 123 (1951). 



199 J. N. Williams, Jr., J. Biol. Chem. 192, 81 (1951). 



2°° J. S. Dinning, C. K. Keith, P. L. Davis, and P. L. Day, Arch. Biochem. 27, 89 

 (1950). 



201 J. N. Williams, Jr., Proc. Soc. Exptl. Biol. Med. 78, 206 (1951). 



202 L. S. Dietrich, W. J. Monson, and C. A. Elvehjem, J. Biol. Chew. 199, 2 (1952). 

 2''3 E. L. Oginsky, Arch. Biochem. 26, 327 (1950). 



21)4 H. R. V. Arnstein and A. Neuberger, Biochem. J . 48, ii (1951). 



