The physiological action of thiamine analogues in thiamine dependent systems

The physiological action of a number of benzyl-(3)-thiazolium analogues of thiamine has been studied in three fundamentally different thiamine systems;The ability of certain of these analogues to inhibit the thiamine stimulated growth of the rat and the bacterium L. fermentum 36 has been demonstrated. The o-aminobenzyl-(3)-4-methyl-5-beta-hydroxyethylthiazolium analogue inhibits the growth of rats but not that of the L. fermentum . The o-aminobenzyl and the gamma-aminopropyl-(3)-4-methylthiazolium analogues are definite inhibitors of the thiamine stimulated growth of the L. fermentum;The ability to stimulate further the growth promoting effect of thiamine for the L. fermentum by many of these analogues has been shown also. Two analogues, the o- and p-aminobenzyl-(3)-4-methyl-5-beta-hydroxyethylthiazolium chlorides, are particularly effective in this respect and to the extent that it must be assumed that the stimulating abilities of these analogues are specific functions of their structure;The specific physiological responses of these systems in the presence of several of these analogues can be correlated with their specific structures as related to themselves as well as to thiamine. A free amino group three carbons removed from the quaternary nitrogen was present in all analogues showing marked inhibition properties. This group in the analogue molecules has approximately the same spatial relationship to the whole analogue molecule as does the free amino group of thiamine to the whole thiamine molecule. The importance of this amino group to both the thiamine and analogue molecules for their activity adds indirect but substantial evidence for the importance of the free amino group for thiamine function;A new and rather peculiar function has been shown for the 5-beta-hydroxyethyl group in the thiazole moiety common to both the analogues studied and the thiamine, in that its presence or absence seems to dictate for the o-aminobenzyl-(3)-4-methylthiazolium analogue of thiamine whether its physiological effect on the thiamine system of L. fermentum is one of marked inhibition or activation;In connection with these studies a different method of assay, the fermenting ability of bakers\u27 yeast, for analogue-thiamine investigation was introduced, tested and evaluated. The preliminary investigation indicated that this assay method is not of general application to analogue-thiamine competition studies