430 VITAMIN Bi2 



in the synthesis of methionine, purines, serine, and thymine. Similarly folic 

 acid has been found to be involved in the synthesis of thymine and purines 

 by L. casei,''^ and of thymidine by Le. mesenteroides,^^ in the conversion of 

 glycine to serine^^ via formate,''^ and of homocystine to methionine. ^"^ This 

 close interrelationship of vitamin B12 and folic acid in biochemical reactions 

 finds its counterpart in the interchangeable effects of these two vitamins 

 in producing a hemopoietic response in pernicious anemia. 



The basis of the relationship between vitamin B12 and folic acid is a 

 subject for speculation. Shive observed that vitamin B12 was able to reverse 

 the toxicity of sulfanilamide for E. coli under highly specific conditions. 

 Since p-aminobenzoic acid would also reverse this toxicity, Shive^^ sug- 

 gested that vitamin B12 was either involved in the conversion of p-amino- 

 benzoic acid to the coenzyme form or it had an independent coenzymic 

 function in the reactions involving the single carbon unit. On the other 

 hand, Davis^^ has discussed the possibility that p-aminobenzoic acid may 

 enter the vitamin B12 molecule as a building stone. The evidence for this 

 was based on the observation that vitamin B12 had a sparing effect on the 

 requirement of certain E. coli mutants for p-aminobenzoic acid. It was 

 also noted that certain mutants ("quintuple auxotrophs") required tyro- 

 sine, phenylalanine, tryptophan, p-aminobenzoic acid, and p-hydroxyben- 

 zoic acid but did not require vitamin B12, perhaps suggesting the structural 

 origin of the benzene ring of vitamin B12 from p-aminobenzoic acid. The 

 molar requirement of E. coli for vitamin B12 was found to be 0.02 of its 

 requirement for p-aminobenzoic acid. 



The discovery that p-aminobenzoic acid was present in the molecule of 



60 D. Elwyn and D. B. Sprinson, /. Biol. Chem. 184, 465 (1950). 



61 D. Shemin, /. Biol. Chem. 162, 297 (1946). 



62 G. C. H. Ehrensvard, E. Sperber, E. Saluste, L. Reio, and R. Stjernholm, /. Biol. 

 Chem. 169, 759 (1947). 



63 P. D. Goldsworthy, T. Winnick, and D. M. Greenberg, J. Biol. Ch-em. 180, 341 

 (1949). 



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

 66 T. Winnick, I. Moring-Claesson, and D. M. Greenberg, /. Biol. Chem. 175, 127 



(1948). 



66 W. Sakami, /. Biol. Chem. 178, 519 (1949). 



67 J. L. Karlsson and H. A. Barker, J. Biol. Chem. 177, 597 (1949). 



68 W. Sakami, Federation Proc. 9, 222 (1950). 



63 W. Shive, Presented at N. Y. Academy of Sciences, S3'mposium on Antimetab- 

 olites, Feb. 11, 1949. 

 " E. E. Snell and H. K. Mitchell, Proc. Natl. Acad. Sci. U. S. 27, 1 (1941). 

 " E. L. R. Stokstad, J. Biol. Chem. 139, 475 (1941). 

 " B. Holland and W. W. Meinke, J. Biol. Chem. 178, 7 (1949). 

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

 74 M. A. Bennett, /. Biol. Chem. 187, 751 (1950). 

 76 B. D. Davis, J. Bacterial. 62, 221 (1951). 



