COENZYMES DERIVED FROM B VITAMINS 201 



condensations are alternately formylated in one reaction and then re- 

 generated by acting as formylating agents in a second. 



Reactions Catalyzed by Coenzymes Derived from p-Aminobenzoic Acid 

 and Folic Acid. Since a direct demonstration of the participation of these 

 vitamins in any defined enzyme system has not been achieved, no equa- 

 tions will be written to depict the specific reactions for which they or 

 their derivatives are required. The following isolated observations, how- 

 ever, can be explained and integrated if one accepts a general hypothesis 

 in which it is assumed that: derivatives of p-aminobenzoic acid function 

 as coenzymes for metabolic reactions in which the single carbon units 

 (related to formic acid) are utilized for synthetic purposes. 



I. Amino Acid Synthesis 



A. Serine and Glycine. A p-aminobenzoic acid coenzyme is required 

 for the reductive condensation by which serine is formed from glycine 

 and formic derivatives, or for the reverse oxidative cleavage by which 

 glycine is produced from serine, because: serine increases the sulfon- 

 amide p-aminobenzoic acid ratio needed to inhibit bacteria 294, 295 ; serine 

 is a precursor of glycine, 296 but in the presence of sulfonamides this con- 

 version cannot take place 297 ; a synthesis of serine from formic acid and 

 glycine has been demonstrated 280,281 ; and folic acid has been shown to 

 be involved in the interconversion of glycine and serine. 298 



B. Methionine. A p-aminobenzoic acid coenzyme is believed to be an 

 essential catalyst for some reaction in the reductive process by which the 

 single carbon unit is converted to an S-methyl group needed for the 

 synthesis of methionine from homocysteine, because: methionine increases 

 the sulfonamide p-aminobenzoic acid ratio needed to inhibit bac- 

 teria, 285, 289 and decreases the requirements of organisms (and mutants) 

 unable to synthesize their own p-aminobenzoic acid 287 ; but homocysteine 

 is ineffective in either of these situations 2 " ; the S-methyl carbon atom 

 of methionine, isotopically labelled, is found to be incorporated into the 

 /^-position when serine is formed biosynthetically from glycine. 282 



II. Purines and Pyrimidines. 



Derivatives of folic acid and p-aminobenzoic acid are presumed to be 

 coenzymes for the reactions in which the single carbon unit is incorporated 

 into purine and pyrimidine nuclei, because: in the presence of amino 

 acids the folic acid requirements of some microorganisms can be replaced 

 by thymine and purines 30 ° ; in the presence of amino acids, the p-amino- 

 benzoic acid requirements of other microorganisms can be replaced by 

 thymine and purines 287 ; in the presence of amino acids the inhibition 

 produced by folic acid analogues can be prevented by thymine and 



