70 



P-AMINOBENZOIC ACID 



coli cultures grown in the presence of just siih-l)acteriostatic amounts of 

 sulfanilamide, and, preferably, increased amounts of glycine,^^ an amine 

 that has been isolated^^ and identified as 5(4)-amino-4(5)-imidazolecar- 

 boxamide.^^ The reaction blocked indirectly by sulfanilamide in the syn- 

 thesis of purines is as follows : 



H2N— C=0 



C— NH 



N=C— OH 



CH 



inhibition 

 index, 30,000~ 



HO- 



C C— NH 

 \ 



H2N— C— N 



5(4)-Ainino-4(5)-imidazole- 

 carboxamide (or riboside) 



N— C— N 



Hypoxanthine 



(or ribose) 



CH 



An increase in the inhibition index from 30,000 to 50,000-100,000 with 

 addition to the Escherichia coli medium now containing methionine and 

 purines may be obtained by addition of serine.-'' These data lead to the 

 conclusion (considerably strengthened by unrelated experiments from other 

 sources) that PABA functions indirectly in the synthesis of serine. 



CH2COOH 



inhibition 



CH2~CHC00H 



index, 50,000-100,000 



NH2 OH NH2 



Glycine Serine 



An increase in the inhibition index from 50,000-100,000 to 200,000- 

 300,000 may now be obtained in the presence of methionine, purines, and 

 serine with either relatively large amounts of thymine or much smaller 

 amounts of folic acid.^^ In this instance the precursor of thymine is un- 

 known. 



HN— C=0 



Unknown precursor 



Inhibition 



index, 200,000-300,000 



-^ 0=C C— CHs 



HN— CH 



Thj'mine (or derivative 

 such as thymidine) 



Although a study of the various compounds that reverse sulfonamide 

 inhibition of microorganisms leads to considerable clarification of the 

 reactions carried out by a metabolically active derivative of PABA whose 



36 J. M. Ravel, R. E. Eakin, and W. Shive, J. Biol. Chem. 172, 67 (1948). 

 " M. R. Stetten and C. L. Fox, Jr., J. Biol. Chem. 161, 333 (1945). 

 38 W. Shive, W. W. Ackermann, M. Gordon, M. E. Getzendaner, and R. E. Eakin, 

 /. Am. Chem. Soc. 69, 725 (1947). 



