THE FOLIC ACID COMPLEX 



acid, were resistant to sulphonamides, but pteroic acid had a slight 

 anti-sulphonamide activity for S. faecalis (Ralston) and S. zymogenes 

 26C1. These observations were interpreted as confirming the theory 

 that pteroylglutamic acid is synthesised from ^-aminobenzoic acid. 



Still further support for this theory was obtained by a comparison 

 of the ability of various compounds related to ^-aminobenzoic acid 

 to replace it as a growth-promoter for L. arahinosus}^ ^-Amino- 

 benzoylglutamic acid, pteroic acid, pteroylglutamic acid and pteroyl- 

 triglutamic acid were all less active than ;/)-aminobenzoic acid, mole 

 for mole. High concentrations of thymine could replace p-d^mmo- 

 benzoic acid but with thymine the presence of a purine was necessary. 



The inhibition of L. arabinosus by sulphanilamide was antagonised 

 non-competitively by pteroylglutamic acid, pteroyltriglutamic acid 

 and by thymine. _^-Aminobenzoyl glutamic acid was about as active 

 as _/)-aminobenzoic acid in antagonising low concentrations of sulphon- 

 amide, but much less active against higher concentrations. _/)-Amino- 

 benzoylglutamic acid and pteroylglutamic acid were less active than 

 _^-aminobenzoic acid on Streptohacterium plantarum, and inhibition of 

 this organism by sulphonamides was antagonised non-competitively 

 by pteroylglutamic acid and by thymine. As with L. arabinosus, the 

 activity of ^-aminobenzoylglutamic acid approached that of _/)-amino- 

 benzoic acid against low sulphonamide concentrations, but was much 

 less against high concentrations. 



It is suggested that pteroylglutamic acid, the purines and thymine 

 are products of enzyine systems in which ;^-aminobenzoic acid functions. 

 _/)-Aminobenzoylglutamic acid appears to be utilised by the two 

 organisms only after conversion into ^-aminobenzoic acid. 



In view of these observations, the reported existence of a con- 

 jugated form of _/)-aminobenzoic acid is of considerable significance. 

 K. C. Blanchard ^' advanced evidence suggesting that, in yeast, 

 j!)-aminobenzoic acid was combined with protein, and Ratner et al.^^ 

 succeeded in isolating a polypeptide containing 8 % of _/)-aminobenzoic 

 acid. This was subsequently shown to be linked through the carboxyl 

 group with a chain of ten or eleven L-glutamic acid residues. This 

 conjugate accounted for 20 to 30 % of the total ^-aminobenzoic acid 

 content of the yeast. Its constitution bears an obvious resemblance 

 to that of vitamin Be conjugate. 



Growth Inhibitors 



Replacement of the methyl group of thymine (page 513) by an 

 amino or hydroxy group resulted in the formation of compounds with 

 inhibitory activity, e.g., 5-hydroxyuracil , 5-aminouracil, 5-carb- 

 amidouracil, and nearly all 2 : 4-diaminopyrimidines and their con- 

 densed ring derivatives.^ Growth was restored by the addition of 



516 



