THE FOLIC ACID COMPLEX 



is not clear whether in this instance xanthopterine is a precursor of 

 folic acid or an essential growth factor for the organism, or whether 

 its similarity to a hypothetical intermediate enables it to inhibit the 

 synthesis or utilisation of the intermediate. It has already been 

 noted (page 461) that the folic acid content of incubated rat liver can 

 be increased by addition of xanthopterine * and here again it is not 

 clear whether xanthopterine is a precursor of folic acid or whether 

 folic acid is converted by enzymes in the liver into a substance that is 

 microbiologically inactive, xanthopterine inhibiting this transforma- 

 tion ; the latter explanation is that favoured by Wright et al. 



Folic acid is also synthesised by E. coli. A. K. Miller ^ observed 

 that less was synthesised in vitro by both sulphonamide-sensitive and 

 sulphonamide-resistant strains when grown in presence of sulphanil- 

 amide than by the same strains when grown in a sulphonamide-free 

 medium ; by contrast, the amount of biotin synthesised by the 

 organisms was imaffected by the presence of the antibacterial drug. 

 These results suggest that the sulphonamides may interfere with the 

 synthesis of folic acid by some micro-organisms, the well-known 

 antagonism between the sulphonamides and p aminobenzoic acid 

 (page 546) extending to folic acid. The inhibitory action of sulpha- 

 diazine on Plasmodium gallinaceum, for example, is completely antago- 

 nised by pteroyl glutamic acid,^° which also partially antagonised 

 the antimalarial activity of chloroguanide. 



The fermentation L. casei factor, pteroyltriglutamic acid, was 

 isolated from a filtrate obtained by aerobic fermentation of an un- 

 identified species of Corynebaderium ^ (page 468). Folic acid is 

 probably synthesised in the intestinal tract by coliform organisms 

 (page 487). 7 



L. arabinosus was shown ^ to synthesise pteroylglutamic acid when 

 excess ^-aminobenzoic acid was present. The amount so produced 

 was dependent on the nature of the amino acids present. Pterojd- 

 glutamic acid and pteroic acid, however, were only a partial substitute 

 for />-aminobenzoic acid for stimulating the growth of L. arabinosus 

 and it is probable, therefore, that ^-aminobenzoic acid has other 

 functions in the bacterial cell besides that of serving as a precursor of 

 pteroylglutamic acid. 



Streptobacterium plantarum also synthesised pteroylglutamic acid. ^ 

 Only glucose and ^-aminobenzoic acid were essential, but glutamic 

 acid had a stimulatory action. The synthesis of pteroylglutamic acid 

 was inhibited by sulphonamides and the inhibition was antagonised 

 competitively by _/)-aminobenzoic acid. 



Flavobacterium buccalis converted pteroylglutamic acid into 

 pteroic acid/^ whilst S. ladis R, 5. faecalis and S. zymogenes con- 

 verted rhizopterine into folic acid or a substance with similar activity.!^ 



510 



