X. I-.KPKCTS OF DEFICIENCY 481 



X. Effects of Deficiency 



THOMAS n. JUKES and WILLIAM L. WILLIAMS 



A. METABOLIC ASPECTS AND FUNCTION OF VITAMIN B12 

 IN MICROORGANISMS 



1. Purine and Pyrimidine Desoxyribosides 



Thymidine was shown by several groups of investigators to be inter- 

 changeable with vitamin B12 for the growth of L. lactis Dorner^ • - and f t)r 

 other lactobacilli.^' ^ The parent pyrimidine, thymine, under the same con- 

 ditions of growth was inactive. These observations on microorganisms 

 served as a basis for speculation on the mechanism of action of vitamin 

 B12 in pernicious anemia. Thus, Wright et air suggested that vitamin B12 

 may function as a coenzyme in carrying out reactions leading to the con- 

 version of thjnnine to thymidine. However, thymidine appears to be no 

 more active than thymine in producing a response in pernicious anemia. 

 Kitay et a/."* showed that thymidine was not the only desoxyriboside which 

 would replace vitamin B12 but that the desoxyribosides of adenine, hypo- 

 xanthine, and cytosine were effective for L. leichmannii 313, L. acidophilus 

 832, and L. acidophilus 4913. The existence of organisms such as L. del- 

 brueckii 730^ and L. acidophilus 204,*- ^ Avhich require thymidine but cannot 

 grow with vitamin B12, and the fact that thymidine does not specifically 

 replace vitamin B12 cast considerable doubt on the theory of Wright et air 

 mentioned above. The interchangeability of the desoxyribosides^ and also 

 the activity of the phosphorylated products, desoxyribotides,^ suggest that 

 these compounds maj'^ simply be providing the groups which they have in 

 common, D-2-desox3a'ibose ; however, tests of both the synthetic compound 

 and a crude natural preparation indicate that D-2-ribose does not promote 

 growth of organisms requiring the desoxyribosides.^ No direct experimental 

 evidence is available, indicating that vitamin B12 functions as a coenzjTiie 

 for the biosynthesis of desoxyribosides. 



2. Effect of Reducing Agents 



Several reports have appeared indicating that chemical reducing agents 

 and reducing conditions obtained bj"" physical means will permit growth of 

 various lactobacilli in the absence of vitamin Bi^.^'^-^ Koditschek et al? 



1 W. Shive, J. M. Ravel, and R. E. Eakin, J. Am. Chem. Soc. 70, 2614 (1948). 



' L. D. Wright, H. R. Skeggs, and J. W. Huff, J. Biol. Chem. 175, 475 (1948). 



3 E. E. Snell, E. Kitay, and W. S. McNutt, /. Biol. Chem. 175, 473 (1948). 



' E. Kitay, W. S. McXutt, and E. E. Snell, /. Biol. Chem. 177, 993 (1949). 



* E. Kitay, W. S. McNutt, and E. E. Snell, /. Bacieriol. 59, 727 (1950). 



« W. Shive, M. E. Sibley, and L. L. Rogers, J. Am. Chem. Soc. 73, 867 (1951). 



7 L. K. Koditschek, D. Hendlin, and H. R. Woodruff, ./. Biol. Chem. 179, 1093 (1949). 



