74 P-AMINOBENZOIC ACID 



COOH 



H2N— <^ ^— CONHCHCH2CH2COOH 



p-Aminobenzoylglutamic acid 



)o-aminobenzoylgliitamic acid is eight to ten times as active as PABA in 

 reversing sulfonamide inhibition of Streptohacteriiim plantarum, p-amino- 

 benzoylghitamic acid otherwise has been found to be less active than PABA, 

 and the reversal obtained is competitive, indicating according to inhibi- 

 tion analysis that p-aminobenzoylglutamic acid is not a product of the 

 reaction inhibited by sulfonamides."- ^^' ^^ 



The synthesis of pteroic acid is a possible site for sulfonamide inhibition. 



OH 



CH2NH— /^ \— COOH 



H2N 



Pteroic acid 



As with p-aminobenzoylglutamic acid, pteroic acid is less active than 

 PABA in reversing sulfonamides, and the reversal so obtained is com- 

 petitive, indicating that pteroic acid is not a product of the reaction in- 

 hibited by sulfonamides."' "^' ^^ Utilization of pteroic acid by Streptococcus 

 faecalis whose "folic acid" requirement can be satisfied with pteroic acid 

 is not inhibited by sulfonamides.^^- ^^ 



O'Meara et al.^^ have suggested that sulfonamides may prevent a com- 

 bination of PABA with reductone, Q:,;S-dihydroxyacrolein, by combining 

 irreversibly with it instead. They picture reductone as being either toxic 

 to the cell or essential at only certain phases of development. It would 

 seem more plausible to consider reductone as an essential intermediate 

 in the synthesis of folic acid and that sulfonamides can interfere with this 

 process. 



N 



OH 



I NH2 CH2COOH 



HO— C=CHOH I 



I CHo 



0=CH 



>- 



H2N— <\ />— CONHCHCOOH 



H2N NH2 



2,4,5-Triamiiio- Reductone p-Aminobenzoylglutamic acid 



6-hydroxypyrimidine 



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



68 R. A. Q. O'Meara, P. A. McNally, and H. G. Nelson, Nature 154, 796 (1944). 



