VITAMINS, ANTIBIOTICS, AND GROWTH 343 



that positions 8a, 4a, and 5 ( see Figure 7 ) were derived from glycine, 

 position 2 from formate, and 4 from carbon dioxide. Folic acid, pur- 

 ines, and pyrimidines did not label leucopterin. Later studies by Jae- 

 nicke (1959) with E. coli indicated that 6, 7, and 9 were derived from 

 ribose. 



In studies with E. coli, Brown (1959, 1960) has found that the 

 pteridine ring in a reduced form combines with para-aminobenzoic 

 acid to form dihydropteroic acid and then with glutamic acid to form 

 dihydrofolic acid (see Figure 11). Apparently it is the combination of 

 para-aminobenzoic acid with the reduced pteridine that is inhibited 

 competitively by sulfanilamide. This interpretation fits in with the ob- 

 servation that sulfonamides inhibit the growth of bacteria that synthe- 

 size folic acid, but animals require preformed folic acid and are not 

 hurt by the sulfonamides. 



The origin of folic acid is thus seen to be predominantly from car- 

 bohydrate and tricarboxylic cycle pathways, with the intriguing ex- 

 ception of the 2-carbon atom, which is derived from "formate" and 

 therefore apparently from folic acid itself through 10-formyl tetra- 

 hydrofolic acid. 



Vitamin B12. Many bacteria and filamentous molds synthesize vita- 

 min B12, but it is not produced by green plants. Animals are dependent 

 upon other animals or microorganisms for their supply of this vitamin, 

 which is remarkable for containing cobalt. The large molecule of vita- 

 min B12 contains the following groupings: 



1. A porphyrin-like structure composed of four pyrrole rings, with 

 acetamide and propionamide side-chains similar to uroporphyrin III, 

 except that in ring C a methyl group replaces the acetamide group, and 

 with eight additional methyl groups. This structure is believed to or- 

 iginate from glycine through delta-amino-levulinic acid and porpho- 

 bilinogen. This is a pathway involving succinyl coenzyme A. The 

 methyl groups are added at a subsequent stage (Figure 8). Cobalt is 

 firmly bound at the center of this structure. 



2. A nucleotide containing 5,6-dimethyl benzimidazole with a 

 molecule of ribose-3-phosphate. The dimethylbenzimidazole grouping 



'. 4 ; /s / ,._ 



^ ! 94a ,' ,' 9 ~^ 



Figure 7. The pteridine ring -"-" IM ni "^^ 



and its biological synthesis. | 3 



