446 VITAMIN Bi2 



modifications of cyanocobalamin. Although the reports are not all conclu- 

 sive, it seems evident that all the substances so far tested possess very 

 nearly the same activity as vitamin B12 in the clinical tests conducted. 

 Quantitative estimates in tests of this nature are very difficult. Hydroxo- 

 cobalamin (vitamins Bi2a or Bi2b) has been found to promote clinical im- 

 provement and produce positive hemopoietic responses in cases with addi- 

 sonian pernicious anemia, tropical sprue, non-tropical sprue, nutritional 

 macrocytic anemia, and with one case of megaloblastic anemia of in- 

 fancy .2^' ^^ Sulfatocobalamin, cyanatocobalamin, and the vitamin B^-hy- 

 drogen sulfide reaction product have been found potent in addisonian 

 pernicious anemia, nutritional macrocytic anemia, and sprue." Vitamins 

 Bi2c and Bi2d (Bi2a) have both been tested clinically in a number of cases 

 of addisonian pernicious anemia and subacute combined degeneration of 

 the spinal cord with the result that no difference could be observed between 

 the activities of these compounds and that of vitamin Bi2.^*' ^^ 



Extensive experiments have been carried out on the relationship of 

 vitamin B12, folic acid, thymine, and uracil in persons with pernicious 

 anemia and related megaloblastic anemias.^" • ^^ It has been concluded from 

 this work, in agreement with previously cited experiments on microbial 

 metabolism,^' ^ that both folic acid and vitamin B12 are involved or are 

 essential to the formation of nucleic acid and nucleoprotein. The suggestion 

 has been made that the megaloblast common to pernicious anemia and 

 related macrocytic anemias is a primitive erythroblast with an abnormality 

 in the metabolism of nucleoprotein due to deficiency of vitamin B12, folic 

 acid, and possibly other chemical activators.^*' 



VI. Biogenesis 



DONALD E. WOLF and KARL FOLKERS 



Production of vitamin B12 is by biosynthesis using fermentation proc- 

 esses. Investigations have been conducted to determine means of increasing 



^^ E. A. Kaczka, R. G. Denkewalter, A. Holland, and K. Folkers, J . Am. Chem. Soc. 

 73, 335 (1951). 



26 T. D. Spies, R. E. Stone, M. B. Koch, H. M. Grant, and M. M. Moore, Southern 

 Med. J. 43, 50 (1950). 



27 E. A. Kaczka, D. E. Wolf, F. A. Kuehl, and K. Folkers, /. Am. Chem. Soc. 73, 

 3569 (1951). 



28 C. C. Ungley and H. Campbell, Brit. Med. J. I, 152 (1951). 

 " J. N. M. Chalmers, Brit. Med. J. I, 161 (1951). 



30 R. W. Vilter, D. Horrigan, J. F. Mueller, T. Jarrold, C. F. Vilter, V. Hawkins and 



A. Seaman, Blood 5, 695 (1950). 

 " D. D. Woods, J. Pharm. Pharmacol. 2, 537 (1950); C. C. Ungley, ibid. 2, 540. 



