COENZYMES DERIVED FROM B VITAMINS 207 



formation of desoxyribosides, either by promoting the synthesis of a 

 reactive derivative of desoxyribose 322 or by catalyzing the union of the 

 sugar with the nitrogen bases. 323 



Vitamin B i2 has since been shown to participate in other types of 

 biosynthetic processes — those by which serine and methionine are formed. 

 This was first demonstrated by the use of sulfonamide inhibition of 

 Escherichia coli. 29St 317 Two other findings offer collaborative evidence 

 for the methionine functions: vitamin Bi 2 can completely replace the 

 methionine necessary to promote the growth of a p-aminobenzoic acid 

 requiring mutant of E. coli, when it is cultured in a medium containing 

 suboptimal amounts of p-aminobenzoic acid 327 ; and the incidence of 

 renal damage in rats resulting from a diet deficient in choline and 

 methionine can be appreciably reduced by the administration of vitamin 

 B 12 . 328 



A very plausible explanation for the manner in which vitamin Bi 2 

 functions has been obtained through the use of inhibitors. 295, 317 In E. coli 

 the biosynthesis of methionine, purines, serine and folic acid (or thymine) 

 by enzyme systems containing p-aminobenzoic acid can be effectively 

 blocked by sulfonamide inhibition. But in each of these four distinct 

 processes the presence of vitamin Bi 2 (0.00005 /xgm/ml) reduces by two- 

 thirds the amount of p-aminobenzoic acid required to counteract the 

 specific inhibition and restores adequate synthesis of the respective com- 

 pounds (section D) . The investigators felt that their results could be best 

 explained by assuming that vitamin B 12 is a catalytic factor necessary for 

 the utilization of p-aminobenzoic acid (and folic acid?). This explanation 

 could be interpreted to mean that vitamin B 12 functions as a catalyst 

 for the formation of the coenzymes necessary in the reactions involving 

 single carbon units. Such a hypothesis seems reasonable and would 

 explain why vitamin Bi 2 is involved in the biosynthesis of a variety of 

 types of chemical compounds. It should be noted that these compounds 

 include all those in which p-aminobenzoic acid and folic acid are definitely 

 known to function (p. 201). It would also imply an independent require- 

 ment of both vitamin B i2 (catalyst for coenzyme formation) and p-amino- 

 benzoic acid or folic acid (substrate for coenzyme formation) . Hence 

 folic acid could not be expected to substitute completely for vitamin Bi 2 

 in the treatment of macrocytic anemias, nor would vitamin B i2 be ex- 

 pected to exhibit appreciable activity in the treatment of blood dyscrasias 

 corrected by folic acid therapy (Chapter VIC). 



It has been suggested on the basis of clinical evidence that vitamin Bi 2 

 is necessary for the conversion of folic acid conjugates to other deriva- 

 tives which are more readily utilized. 329, 330, 331 Although the investigators 

 later retracted their conclusions, 332 a direct demonstration of such a 



