THE FOLIC ACID COMPLEX 



The systematic name of this substance is N-[4-{[(2-amino-4-hydroxy-6- 

 pteridyl-)-methyl]-amino}-benzoyl]-glutamic acid. Fermentation L. 

 casei factor, which was found to contain three glutamic acid residues, 

 was converted into the racemic form of the liver L. casei factor by 

 anaerobic alkaline hydrolysis. The name of the liver factor was 

 abbreviated to pteroyl-glutamic acid, pteroic acid being the short 

 name for 4-{ [(2-amino-4-hydroxy-6-pteridyl)-methyl]-amino}-benzoic 

 acid. The latter was synthesised by a method similar to that used 

 for the synthesis of the L. casei factor (see page 474), and was found 

 to be active for S. faecalis R, but inactive for L. helveticus and the 

 chick. Its biological activity thus resembled that of the SLR factor, 

 although the two are not identical (page 473). The fermentation 

 L. casei factor, containing three glutamic acid residues, was given the 

 name pteroyldiglutamylglutamic acid or, more briefly if less accurately, 

 pteroyltriglutamic acid, whilst yeast vitamin Be conjugate, which 

 contained seven glutamic acid residues,^® was called pteroylhexa- 

 glutamylglutamic acid or pteroylheptaglutamic acid. 



The heptaglutamate was essentially inactive on micro-organisms 

 whereas the triglutamate was active. Since vitamin Be conjugase 

 converted the conjugate into vitamin Be, it must be classified as a 

 peptidase and, since it did not liberate vitamin Be from the methyl 

 ester of the conjugate, it must be a carboxy peptidase. Finally, since 

 it liberated glutamic acid from ^-aminobenzoyl-y-glutamyl-y-glut- 

 amylglutamic acid, from synthetic pteroyltriglutamate and from the 

 natural fermentation factor, but not more than i molecular equivalent 

 in each instance, it must be classified as a y-glutamic acid carboxy- 

 peptidase, requiring at least two terminal glutamic acid molecules in 

 a peptide chain. ^^ 



The constitution of folic acid itself has not been conclusively 

 settled, as it has not been isolated in the pure state. According to 

 D. A. Hall,^o however, a folic acid concentrate prepared from spinach 

 exerted a synergistic action on synthetic pteroylglutamic acid, so that 

 folic acid cannot be identical with pteroylglutamic acid. Synergism 

 was similarly observed between pteroylglutamic acid and a concentrate 

 prepared from poppy-straw, but not a similar concentrate from liver. 

 This is taken to indicate that " folic acid " from vegetable sources is 

 different from " folic acid " of animal origin. 



References to Section 1 



1. H. K. Mitchell, E. E. Snell and R. J. Williams, /. Amer. Chem. 



Soc, 1941, 63, 2284. 



2. E. E. Snell and W. H. Peterson, /. Biol. Chem., 1939, 128, xciv ; 



/. Bad., 1940, 36, 273. 



3. E. L. R. Stokstad, /. Biol. Chem., 1941, 139, 475. 



464 



