692 THE BIOCHEMISTRY OF B VITAMINS 



of thiamine, nevertheless it appears that vitamin Bi is required in their 

 metabolism, and the results of the experiments with analogues of the 

 pyrimidine and thiazole components of thiamine (summarized in Tables 

 43 and 44) indicate that for many microorganisms the structural spec- 

 ificity of vitamin Bi is substantially the same as for animals. 



Recently it was reported that the administration of lumazine, xanthop- 

 terin, isoxanthopterin or folic acid to rats and pigeons on a low thiamine 

 diet not only restores chronaxia to normal, but also cures polyneuritis 

 and permits normal growth. This effect is observed when these compounds 

 are injected into normal rats and when they are administered to cae- 

 cumectomized rats, which indicates that their activity is not due to the 

 synthesis of extra thiamine by the intestinal flora. However, these com- 

 pounds do not replace thiamine as growth factors for Glaucoma or for 

 Polytomella caeca. These results suggest that these compounds may exert 

 a sparing action on thiamine but are not able to replace it entirely. 



Bonner 67 has shown that pea roots require both the pyrimidine and 

 thiazole components of thiamine for growth. Growth tests with analogues 

 (Tables 43 and 44) indicate that their structural requirements for vita- 

 min Bx activity are not quite so stringent as those of many other or- 

 ganisms. Recently it was reported that 4-methyl-5-thiazoleacetamide 

 stimulates plant germination. 69b 



The possibility that the thiazole portion of thiamine may be derived 

 from an amino acid precursor, /?-(4-methylthiazolyl-5) -alanine, was early 

 considered. 68, 69 While neither Staphylococcus aureus nor Phycomyces 

 blakesleeanus utilized the amino acid derivative, the compound replaced 

 the thiazole moiety in stimulating pea roots. 



By assay with Phycomyces blakesleeanus, the formation by pea roots 

 of the thiazole portion of thiamine was demonstrated with this amino acid 

 as well as with 4-methylthiazole derivatives with the following substitu- 

 ents in the 5-position: -CH 2 -CH 2 C1, -CH = CH 2 , -CH 2 -CH 2 NH 2 , 

 and — CH 2 — CH 2 OH. However, with 4-methylthiazole derivatives con- 

 taining either -CHOH-CH 3 or -CH.-CHOH-CH-, at position 5, and 

 with — CH 2 — CH 2 OH and — CH 3 at positions 5 and 2, respectively, syn- 

 thesis of the thiazole moiety by pea roots could not be demonstrated. 67 * 1 

 Consequently, since the last compounds are also effective in promoting 

 growth of pea roots, it appears that these compounds possess activity 

 without prior conversion to the normal thiazole moiety, while the activity 

 of the other compounds may be ascribed at least in part to their conver- 

 sion to the normal metabolite. The mode of action of these compounds 

 which are not converted to the thiazole moiety is still obscure since 

 analogues of thiamine possessing some of these modifications are inactive 

 for pea roots (Table 42). 



