IV. BIOCHEMICAL SYSTEMS 431 



pteroylglutamic acid^* made it seem that the sole function of p-amino- 

 henzoic acid might be to serve as a precursor of folic acid, and indeed this 

 seemed possilile in the case of S. faccalis Ralston, which was found by 

 Lampen and Jones" to utilize pteroylglutamic acid as a non-competitive 

 antagonist for sulfanilamide. This indicated that sulfanilamide inhibited 

 this organism solel}^ by blocking the conversion of p-aminobenzoic acid to 

 folic' acid. However, for many microorganisms, p-aminobenzoic acid cannot 

 be replaced by folic acid as a growth factor,^^- ^^' " thus making it evident 

 that p-aminolienzoic acid has functions other than that of serving as a 

 precursor of folic acid. To interpret the existing obseivations, Shive^^ in- 

 clines to the viewpoint that p-aminobenzoic acid and folic acid may be the 

 precursors of a single coenzyme and that organisms differ in their ability 

 to utilize the two respective precursors in the formation of the coenzyme. 

 However, this explanation does not appear to be full enough to account 

 for the suggestion by Davis^^ that p-aminobenzoic acid may be a precursor 

 of vitamin B12. Again, if one assumes that p-aminobenzoic acid and folic 

 acid may both serve in the formation of the same coenzyme and that the 

 utilization of p-aminobenzoic acid for this purpose is catalyzed by vitamin 

 B12 as follows: 



p-Aminobenzoic acid -^ — > Coenzyme < — Folic acid 



it would then be difficult to account for the observation that many species, 

 such as chicks,*" rats,^* and human beings,*^ require both vitamin B12 and 

 folic acid. A deficiency of folic acid appeared to be intensified by the 

 administration of vitamin B12 in the report by Day and coworkers.^^ This 

 would appear to rule out the possibility that vitamin B12 and folic acid 

 contribute toward the fonnation of the same coenzyme. Chicks will develop 

 folic acid deficiency even when vitamin B12 and p-aminobenzoic acid are 

 both supplied ;*° indeed, there is no coherent evidence that the latter sub- 

 stance plays a role in animal nutrition as a dietary essential or otherwise. 

 A functional derivative of folic acid, the citrovorum factor (CF), is 

 needed by Leuconostoc citrovorum and is more effective than pteroylglutamic 

 acid in reversing the toxicity of certain "folic acid antagonists."*-- *^ It is 



^« R. B. Angler, J. H. Boothe, B. L. Hutchings, J. H. Mowat, J. Semb, E. L. R. 



Stokstad, Y. SubbaRow, C. W. Waller, D. B. Cosulich, M. J. Fahrenbach, M. E. 



Hultquist, E. Kuh, E. H. Northey, D. R. Seeger, J. P. Sickels, and J. M. Smith, 



Jr., Science 103, 667 (1946). 

 " J. O. Lampen and M. J. Jones, J. Biol. Chem. 164, 485 (1946). 

 " J. 0. Lampen, M. J. Jones, and R. R. Roepke, J. Biol. Chem. 180, 423 (1949). 

 " N. S. Cutts and C. Rainbow, A^a^ure 164, 234 (1949). 

 8« E. L. R. Stokstad and T. H. Jukes, Proc. Soc. Exptl. Biol. Med. 62, 112 (1946). 



81 L. A. Day, B. E. Hall, and G. L. Pease, Proc. Staff Meet. Mayo Clinic2i, 119 (1949). 



82 H. E. Sauberlich and C. A. Baumann, J. Biol. Chem. 176, 165 (1948). 



