COENZYMES DERIVED FROM B VITAMINS 203 



If only coenzymes common to both vitamins exist, there must be two 

 alternative routes for their syntheses: (1) one in which folic acid is first 

 synthesized from p-aminobenzoic acid or else must be supplied preformed 

 to the organism (in which case p-aminobenzoic acid might be ineffective 

 as a substitute for folic acid) ; and (2) one in which the order of the 

 assembling of the components is such that folic acid does not constitute 

 an intermediate (in which case folic acid might be ineffective as a sub- 

 stitute for p-aminobenzoic acid).* 



Biosynthesis of the Coenzymes. Although the chemical nature of the 

 biosynthetic processes by which coenzymes are formed from folic acid 

 and p-aminobenzoic acid is unknown, mention should be made of four 

 observations which may have some bearing on mechanisms of the con- 

 version of the vitamins to their active forms. (1) The occurrence and 

 activities of the formyl derivatives of folic and pteroic acids have been 

 previously pointed out; the formylation of the amino group of a p-amino- 

 benzoyl moiety may be a reaction occurring at some stage in the forma- 

 tion of the coenzymes. (2) An enzyme, designated as vitamin B c conjugase 

 by its discoverers, catalyzes the hydrolysis of the polyglutamyl deriva- 

 tives of folic acid which have been found to occur in yeast, plant, and 

 animal tissues 302 ; this enzyme may catalyze reactions necessary for con- 

 verting the pteroyl polypeptides into a form which can be used for co- 

 enzyme synthesis. (3) Vitamin Bi 2 has been postulated as functioning 

 in the utilization of p-aminobenzoic acid, probably by promoting some 

 reaction which is a necessary step in producing the active cofactors of 

 p-aminobenzoic and folic acids (p. 207). (4) The amount of folic acid 

 necessary to cause a remission in pernicious anemia is markedly decreased 

 if the vitamin is first incubated with a liver preparation of "xanthopterin 

 oxidase." 303 Folic acid, when incubated either with concentrates pos- 

 sessing xanthine oxidase activity or with crude extracts of gastric mucosa 

 is reported to be "activated" in a fashion such that it has vitamin Bu 

 activity (p. 16), i.e., it can (a) stimulate erythropoiesis in bone marrow 

 tissue cultures and (b) inhibit proliferation of tumor cells cultured in 

 vitro. Untreated folic acid is inactive. No further information on the 

 chemical or functional relationship of vitamin B14 and folic acid has 

 been disclosed. 



* An announcement of the natural occurrence of a group of substances structurally 

 and functionally related to folic acid which are 100 times as active as folic acid in 

 preventing the inhibition of a folic acid inhibitor was made in November, 1949 

 (Bond, T. J., Bardos, T. J., Sibley, M., and Shive, W., J. Am. Chem. Soc, 71, 3852 

 (1949)). These forms of the folic acid vitamin, designated the folinic acid group, 

 replace the thymidine requirement of an organism which does not utilize folic acid 

 itself. Hence, this group may constitute folic acid coenzymes or be compounds more 

 complex than folic acid itself which are elaborated during the synthesis of the 

 coenzyme (s). 



