XIII. SULFONAMIDE HEVKUHAL 7 1 



sonc (hat is altered in the sulfoiianiide-requiring strain proihices a dele- 

 terious reaction in Xeiirospora crassa with the following characteristics: 

 (1) it requires a precursor of methionine as substrate, and the amount re- 

 ((uired is greater than that needed for essential reactions normally using 

 the same substrate; (2) it requires PABA as a catalyst, and in much larger 

 amounts than are required V)y other reactions using the same catalyst; (3) 

 at the same time sulfanilamide is a much stronger competitor of PABA in 

 this reaction than in other reactions requiring PABA as a catalyst; and (4) 

 the reaction, or a product of the deleterious reaction, interferes with the 

 noinial utilization of threonine. That the step in threonine utilization 

 interfered with may involve amination is suggested by the growth-pro- 

 moting activity of free ammonia. 



As demonstrated by the content of the foregoing paragraphs, most of the 

 studies that have involved relationships between PABA and the sulfon- 

 amides have been carried out on bacteria. That antagonism between PABA 

 and the sulfonamides may be demonstrated in a variety of plant and ani- 

 mal systems has been demonstrated. Terzian^^ has reported that sulfanil- 

 amide or sulfadiazine in the diet of the mosquito Aedes aegypti will increase 

 the insect's susceptibility to the malarial parasite Plasmodium gallinaceum. 

 PABA fed along with the sulfonamide nullifies its effect on susceptibility 

 of the host. Hindmarsh^^ lias shown with onion rootlets that sulfanilamide 

 prevents the nuclei from coming into prophase and upsets the spindle 

 mechanism so that anaphase rarely occurs. These effects are reversed by 

 PABA. Schopfer and Anker^^ found that PABA, guanine, adenylic acid, 

 and riboflavin exert an antagonistic effect on sulfonamide inhibition of 

 the growth of pea roots in aseptic culture. The growth-inhibiting action of 

 the sulfonamides on growth of pepper grass (Lepidium sativum) roots was 

 found by Andus and QuasteF to be neutralized by PABA. Sulfonamide 

 inhibition of blood carbonic anhj^drase is reversed with PABA according to 

 van Goor.^^ PABA is an antagonist of the inhibiting action of sulfanil- 

 amide on germination and growth of flax seed in the experiments of Ha- 

 zard.*^ Maier and Piley^^ found that the therapeutic effect of the sulfon- 

 amides on Plasmodium gallinaceum infections of chicks is negated by 

 administration of PABA. Sulfonamide inhibition of yeast growth is re- 

 versed by PABA.*^ Growtli of isolated tomato roots is inhibited by sul- 



8' L. A. Terzian, J. Infectious Diseases 87, 285 (1950). 



82 M. M. Hindmarsh, Nature 163, 610 (1949). 



" W. H. Schopfer and W. Anker, Experientia 5, 117 (1949). 



8< L. J. Andus and J. H. Quastel, Ann. Botat)y 12, 27 (1948). 



*^ H. van Goor, Enzymologia 11, 174 (1944). 



8«R. Hazard, Compt. rend. soc. biol. 138, 972 (1944). 



" J. Maier and E. Riley, Proc. Soc. Exptl. Biol. Med. 50, 152 (1942). 



88 M. Landy and D. M. Dicken, Nature 149, 244 (1942). 



