492 THE BIOCHEMISTRY OF B VITAMINS 



Two different explanations for the various published data interrelating 

 p-aminobenzoic acid and folic acid are possible. Folic acid can be con- 

 sidered as differing from the normal metabolic intermediate in the biosyn- 

 thesis of the coenzyme derived from p-aminobenzoic acid; and organisms 

 would be expected to have varying abilities to utilize folic acid in forming 

 the coenzyme. In Escherichia coli, the addition of a number of products 

 (methionine, purines and serine) might be expected to exert a sparing 

 action such that the small amount of folic acid utilized by the organism 

 would be sufficient for growth. This explanation would conform to the 

 theory that a single coenzyme is derived from both p-aminobenzoic acid 

 and folic acid. 



The other explanation would require that more than one coenzyme is 

 formed from folic acid and p-aminobenzoic acid. Thus, folic acid would 

 perform only part of the biochemical functions of p-aminobenzoic acid. 

 The data which are difficult to explain by such a theory include the ability 

 of folic acid to prevent completely the toxicity of sulfonamides and to 

 fulfill the growth requirements in place of p-aminobenzoic acid for cer- 

 tain organisms. If this second explanation is valid, such data would indi- 

 cate that a rapid conversion of folic acid to the other coenzymes 

 occurs by a process resistant to sulfonamides, or that the products of the 

 functioning of the coenzyme derived from p-aminobenzoic acid but not 

 folic acid are supplied in the medium of such organisms. 



Although published reports do not indicate conclusively whether or not 

 two or more coenzymes are derived from p-aminobenzoic acid and folic 

 acid, the low activity of folic acid for many organisms suggests that 

 other active forms of the vitamin will be found. 



The exact biochemical step in the conversion of p-aminobenzoic acid 

 to folic acid which is prevented by sulfonamides has not been elucidated. 

 It is interesting that pteroic acid and p-aminobenzoylglutamic acid 

 reverse the toxicity of sulfonamides competitively, so that neither repre- 

 sents the product of the inhibited enzyme system. Since both p-aminoben- 

 zoylglutamic acid and pteroic acid are less effective than p-aminobenzoic 

 acid over a range of concentrations (Table 3), it appears that the bio- 

 synthesis of folic acid does not proceed through these compounds as 

 intermediates. It has been suggested that sulfonamides may prevent a 

 combination of p-aminobenzoic acid with reductone — a, /3-dihydroxy- 

 acrolein. If so, this may represent a stage in the biosynthesis of folic acid, 

 but convincing biochemical evidence has not been presented. 85 2-Amino- 

 4-hydroxypteridine-6-carboxaldehyde has been suggested as a possible 

 intermediate which is prevented by sulfonamide from combining with 

 p-aminobenzoic acid. 86 Only glucose and p-aminobenzoic acid are essen- 

 tial, and glutamic acid is stimulatory in the biosynthesis of microbiologi- 



