Studies on Thiamine Analocues

Several analogues of thiamine’ are known to compete with the vitamin when administered to animals. Thus, Woolley and White (1) have observed that pyrithiamine caused the manifestation of typical thiamine deficiency symptoms, which could be competitively overcome by the vitamin. The antivitamin effect of oxythiamine in mice has been reported by Soodak and Cerecedo (2). Cerecedo et al. (3, 4), comparing the effects of oxythiamine with those of neopyrithiamine in mice, have found the latter to be far more toxic. The observation of Buchman et al. (5) that the enzymatic decarboxylation of pyruvate by dried brewers’ yeast could be inhibited by thiazole pyrophosphate, and not by thiazole, suggested the possibility of a competition between cocarboxylase and thiazole pyrophosphate for the apoenzyme. This view has been further borne out by the results of Eusebi and Cerecedo (6, 7), demonstrating the inhibition of yeast carboxylase by oxythiamine diphosphate. A confirmation of this work has been reported by Velluz and Herbain (S), who have brought about inhibition of dried yeast carboxylase with oxythiamine triphosphate. Woolley (9) has reported inhibition of yeast carboxylase with neopyrithiamine pyrophosphate and decreased formation of cocarboxylase from thiamine in chicken blood due to neopyrithiamine. With the publication of methods of obtaining more satisfactory preparations of ar-carboxylase by Singer and Pensky (lo), and of thiamine phosphorylase by Leuthardt and Nielsen (II), it was deemed of interest to investigate further the mode of action of several thiamine analogues. The results of these investigations upon the two enzyme systems are reported in this study.