XIII. SULFONAMIDE REVERSAL 75 



It has been suj2;sested by Tschesche^'-' that siilfoiuunides interfere with 

 the conjujj;ation of 2-amino-4-hydroxypteridiiie-()-ul(lehyde with PABA, 

 but stroiiji; experimental evidence for the hypothesis is lackinji;. 



OH 



1 ^"^ 



H2N 



2-Amino-4-hydroxy- 

 pteridine-G-aldoliyde 



Recent studies indicate that folinic acid, the Leuconosfoc citrovorum 

 factor or o-formyl-5,G,7,8-tetrahydropteroylgkitamic acid, is nearer to 

 the form in which foHc acid functions in metabohsm. It is not impossible 

 that folic acid is an artifact that does not actually occur in the normal 

 sequence of PABA utilization. 



That sulfonamides actually interfere with the uptake of PABA by bac- 

 terial cells has })een shown by Noll et al.""^ in studies with Escherichia coli 

 and S^'-labeled sulfathiazole. Competitive interference as determined by 

 radioactivity counts was demonstrated between sulfathiazole and PABA. 



A consideration of the deficiencies produced in animals by the feeding 

 of a poorly absorbed sulfonamide in conjunction with highly purified diets 

 containing only thiamine, riboflavin, pantothenic acid, vitamin Be , nico- 

 tinic acid, and choline as a source of B vitamins is most logically presented 

 in the chapter on folic acid. Mention is made here of the extent to which 

 PABA has been found to reverse the growth-inhibiting effect of the sul- 

 fonamides. 



Black ct al}^' '' found that PABA reverses the growth-inhibiting effects 

 of sulfaguanidine (sulfanilyl guanidine) when this compound is fed to rats 

 to the extent of 0.5 % of a highly purified diet, provided that the PABA 

 is given from the start of the experiment. If PABA is given after a nutri- 

 tional deficiency has been developed by the feeding of the drug, some lag 

 period is observed before the beneficial effects of the PABA become ap- 

 parent. The growth-promoting effect of PABA in ])urified diets containing 

 sulfaguanidine first observed l)y Black e( al.^^- "' has lieen confirmed by IMar- 

 tin^^ and by MacKenzie et aZ.^" 



Wolch^'' loported that PAB.V does not antagonize the gi'owih inhil)ition 

 l)roduced by .sulfasuxidino (succinylsuli'athiazole) when (his compound is 



" R. Tschesche, Z. Naturfmsch . 2b, U) (1947). 



'"> H. XoU, .1. Bang, K. Sorkiii, and II. Kilonmeyor, Heli>. Chim. Ada 34, .340 (10.51). 

 " S. Black, 1{. S. Overman, C. A. Klvolijoni, and K. P. T.ink, ./. Biol. ('hr»>. 145, 137 

 (1942). 



