582 THE BIOCHEMISTRY OF B VITAMINS 



7-Hydroxy-9-oxofolic acid (2-amino-4,7-dihydroxypteridine-6-carbox- 

 ylyl-p-aminobenzoylglutamic acid) , which is more effective as an inhibitor 

 of growth of Lactobacillus casei than of Streptococcus faecalis R, con- 

 trasts with a number of the other analogues listed in Table 19 which are 

 more effective in preventing growth of Streptococcus faecalis R. Whereas 

 1 mg per day of this compound injected intraperitoneal^ is tolerated by 

 rats weighing approximately 125 g, a single dose of 10 mg is fatal within 

 24 hours. Simultaneous administration of 10 y of folic acid prevents the 

 toxicity of the analogue. 



An isomer of the 7-hydroxy-9-oxofolic acid with the 6- and 7-substitu- 

 ents exchanged (2-amino-4,6-dihydroxypteridine-7-carboxylyl-p-amino- 

 benzoylglutamic acid) is less than one-third as active as the isomer with 

 the general structure corresponding to folic acid. 



Pteroylaspartic Acids. N-Pteroyl-L-aspartic acid inhibits the growth 

 of both Lactobacillus casei and Streptococcus faecalis R, as indicated in 

 Table 19. If pteroic acid, pteroyl-y-glutamylglutamic acid, or pteroyl- 

 di-y-glutamylglutamic acid are employed in place of folic acid for Strep- 



OH 



I 

 C N i k 



N C C— CH 2 — NH— ([ V-CO— NH— CH— CH 2 — COOH 



i ii i X=J i 



H 2 N— C C CH COOH 



N N 



N-pteroyl-Jj-aspartic acid 



tococcus faecalis R, the inhibition indices for half maximum growth are 

 2-3, 4.2-17.2 and 0.21-0.32, respectively. Folic acid with an index of 

 37-55 prevents the toxicity of the inhibitor most effectively ; the trigluta- 

 mate is least effective. 



A marked decrease in growth rate and decreased hemoglobin levels 

 are observed in chicks receiving the inhibitor, which causes these defi- 

 ciency symptoms to appear when administered at 500 times the concen- 

 tration of folic acid. 



Administration of the inhibitor to rats at concentrations up to 4.5 mg 

 per day did not cause any significant decrease in growth rate or the ap- 

 pearance of deficiency symptoms even with animals receiving carboxy- 

 sulfathiazole. 



N-(x-Methylpteroyl)-L-aspartic acid is somewhat less effective than 

 pteroylaspartic acid in preventing the utilization of folic acid by Strep- 

 tococcus faecalis R. 



