THIAMINE 687 



able of growth without an external supply of either of these components or 

 thiamine. These requirements are summarized in Table 41. Some strains 

 of Neisseria gonorrhoeae, when first isolated from a human host, cannot 

 utilize thiamine but require cocarboxylase. 25a 



Organisms which require only one or both of the components of thia- 

 mine rather than the intact molecule or do not require an external supply 

 of thiamine or its components apparently achieve partial or in the latter 

 case complete synthesis of thiamine. For example, Bacillus subtilis can 

 be grown in a thiamine-free medium, and the resulting broth will sup- 

 port the growth of Staphylococcus aureus, which requires thiamine or its 

 two components. 26 Moreover, although Mucor ramannianus requires the 

 thiazole component and Rhodotorula rubra requires the pyrimidine com- 

 ponent of thiamine, these two organisms can grow together in thiamine- 

 free media. 27 Katznelson 27a reported that Bacillus paraalvei requires 

 thiamine or a mixture of its components, or at least the thiazole com- 

 ponent, for growth in a medium devoid of cystine, phenylalanine, valine 

 and leucine. Given the three last-named amino acids with either cysteine, 

 glutathione, or cystine (in a reducing medium) or even sodium thiogly- 

 colate or sodium thiosulfate or ascorbic acid, this organism can grow 

 without added thiamine or its components. These results suggest that 

 this organism requires thiamine in its metabolism but in adequate media 

 is able to synthesize the thiamine it requires. 



The biological activity of a large number of analogues of thiamine and 

 its pyrimidine and thiazole components has been determined, as indicated 

 in Tables 42, 43, and 44. As a result of these tests, it is evident that the 

 thiamine molecule can undergo very little modification without extensive 

 loss of vitamin B x activity. Substitution of an ethyl, propyl or iso- 

 propyl group for the 2'-methyl group or an ethyl group for the 4-methyl 

 group are the only modifications which did not produce drastic reduction 

 in the vitamin B x activity. In addition to the skeletal structure of thi- 

 amine, the 4'-amino group, the 5-/3-hydroxyethyl group and the absence 

 of substitution in the 2-position appear to be essential for significant 

 vitamin B x activity. 



A number of thiamine analogues containing a pyridine ring instead of 

 the thiazole ring 58 ~ 63 have been found to be inactive in growth tests on 

 the pigeon, the rat, and several microorganisms. The fact that two of 

 these analogues are active in stimulating the production of carbon dioxide 

 by yeast 63 is due to the ability of the yeast to cleave these analogues and 

 use them as a source of the pyrimidine component of the thiamine mole- 

 cule. 



Although many microorganisms can synthesize thiamine when supplied 

 with suitable intermediates and thus do not require an external supply 



