198 THE BIOCHEMISTRY OF B VITAMINS 



Recent studies with isotopic nitrogen have indicated that this concept is 

 invalid, since the nitrogen atoms of the imidazole ring of histidine are 

 not used in the formation of purines. 284 However, the formic acid or a 

 derivative arising from the hydrolysis of the N = C — N bonds of histidine 

 by histidinase could serve as the source for the single carbon units needed 

 in purine synthesis, and the histidine effect could be entirely attributed 

 to its activity as a formic-donor. It has not been shown whether or not 

 the ureide carbon atoms of purines and pyrimidines can be effectively 

 used as sources for the single carbon intermediate (in reactions which 

 reverse the processes of their syntheses). Neither serine, glycine, methi- 

 onine, choline, nor histidine can be considered as primary sources of 

 the single carbon unit in organisms which do not require an exogenous 

 supply of these substances. 



Vitamins Associated with the Metabolism of the Single Carbon Unit. 

 Both p-aminobenzoic acid-containing coenzymes and vitamin B i2 

 (derivatives?) are catalysts in some stages of the processes by which 

 formic acid or its derivatives are utilized for synthetic purposes. 



Coenzymes Derived from p-Aminobenzoic Acid and Folic Acid 



The specific enzyme systems in which folic acid and other p-amino- 

 benzoic acid derivatives participate are not as yet known. In no instance 

 can we be certain of the exact structure of the compounds entering into 

 or produced by the individual reactions, nor do we know the chemical 

 components of the coenzymes derived from these vitamins. However, a 

 general hypothesis which explains most of the biochemical reactions in 

 which these vitamins are implicated can be arrived at from information 

 acquired during the course of a number of investigations whose primary 

 objectives were entirely unrelated. 



Exploration of the mechanism of sulfonamide inhibition led not only 

 to the recognition of the vitamin activity of p-aminobenzoic acid, but 

 also to the establishment of a metabolic relationship between p-amino- 

 benzoic acid and purines, pyrimidines, and certain amino acids; all these 

 substances can at least partially overcome the toxic effect of sulfonamides 

 upon bacterial growth (Chapter II D) . However, the manner in which the 

 amino acids and nitrogen bases acted as "reversing agents" and their 

 relationship to p-aminobenzoic acid were at first obscure. It was suggested 

 that they might be products of reactions involving p-aminobenzoic acid 

 and that the presence of sulfonamides suppressed their synthesis. 285 



Subsequent studies on the nutritional requirements of organisms and 

 mutants requiring an exogenous supply of p-aminobenzoic acid or folic 

 acid demonstrated that here also the amounts of these vitamins needed 



