76 P-AMINOBENZOIC ACID 



included in a purified diet to the extent of 1 %. Other more extended studies 

 from the same^^ '^-''^ and other laboratories'^^- ^^ have shown that PABA 

 does have a certain small effect in reversing sulfasuxidine, especially with 

 respect to reversing the incidence of the induced hypoprothrombinemia. 

 The failure to observe complete reversal with PABA of the growth in- 

 hibition produced by the incorporation of succinylsulfathiazole in highly 

 purified diets, as contrasted with the reversal of soluble sulfonamides in 

 vitro, probably is attributable to absorption of PABA early in the gut so 

 that the compound does not reach the cecum and large intestine in effec- 

 tive concentration. 



Emerson and Cushing^^- '^^ have described a unique mutant of Neuro- 

 spora crassa that requires sulfanilamide or other similar sulfonamide for 

 growth at 35°. At 30° or lower, sulfonamides are not strictly essential, but 

 growth rates are lower in their absence. For this strain PABA is an in- 

 hibitor that is competitively antagonized by sulfanilamide with an in- 

 hibition ratio for one-half maximum growth of about 100. Another mutant 

 obtained by crossing the sulfonamide-requiring mutant with a PABA- 

 requiring mutant requires both sulfonamide and PABA for growth. The 

 molar ratio giving maximum growth at 35° is about 1000 of sulfanilamide 

 to 1 of PABA. The possibility that sulfanilamide is utilized as a metabolite 

 by the sulfonamide-requiring strain was entertained,'^^ but it has been ruled 

 out by Zalokar,^^ • ^^ who showed that the sulfonamide-requiring mutant 

 may be made to grow by any one of the following ways: (1) by the presence 

 of sulfonamide; (2) by reducing available PABA by genetic means, that is, 

 by crossing the sulfonamide-requiring mutant with a PABA-requiring 

 mutant to give a strain that does not synthesize PABA in large amounts; 

 (3) by reducing available methionine by genetic means, that is, by similarly 

 crossing the sulfonamide-requiring strain with a methionine-requiring 

 strain to give a new strain that does not synthesize methionine in large 

 amounts; (4) by the addition to the medium of threonine, which acts as an 

 inhibitor; or (5) by making free ammonia available as a nitrogen source. 

 As summarized by Zalokar^" the data are best interpreted as follows: The 



'2 L. D. Wright and A. D. Welch, Science 97, 426 (1943). 



" L. D. Wright and A. D. Welch, ,/. Nutrition 27, 55 (1944). 



'" L. D. Wright, H. R. Skeggs, A. D. Welch, K. L. Sprague, and P. A. Mattis, /. 



Nutrition 29, 289 (1945). 

 '5 F. W. Neumann, M. M. Krider, and H. (1. Day, Proc. Soc. Exptl. Biol. Med. 52, 



257 (1943). 

 '«H. G. Day, K. G. Wakim, M. M. Krider, and K. K. O'Banion, ./. Nutrition 26, 



585 (1943). 

 " S. Emerson and J. E. Gushing, Federation Proe. 5, 37i) (194G). 

 ^^S. Emerson, J. Bacteriol. 54, 195 (1947). 

 'i* M. Zalokar, Proc. Natl. Acad. Sci. U. S. 34, 32 (1948). 

 8»M. Zalokar, ./. Bacteriol. 60, 191 (1950). 



