Growth Stimulating Effect of 4-Methyl-5(2-Hydroxyethyl) Thiazole on Thiamine-Deficient Rats. ∗

Abstract

It is well known that 4-methyl-5 (2-hydroxyethyl) thiazole (MHET) can replace thiamine as a nutrient for some bacteria (1). Abderhalden (2,3) without success attempted to demonstrate that MHET could replace thiamine in the diet of the rat. Since then, MHET and the pyrimidine moiety of thiamine (2-methyl-4-amino-5-hydroxymethyl pyrimidine) have been isolated from urine of rats after givin large doses of thiamine (4,5), suggesting that the rat is capable of cleaving thiamine to give these two products. Also Van Eys (6) has identified MHET as a component of glycerol phosphate dehydrogenase, which indicates a strong possibility that MHET is biologically active. It, therefore, seemed desirable to investigate once again the possibility that MHET is biologically active. As workers in the past have apparently achieved essentially negative results (2,3,6,8) our experimental approach involved 3 special considerations.

1. From chemical considerations it seemed possible that MHET, if not carefully prepared, may not be biologically active. To prepare MHET the cleavage of thiamine by the Williams reaction (9) was selected as a mild and direct method. Moreover, the starting material, thiamine, contains a thiazolium moiety which has been shown to be biologically active (10,11).

2. If MHET is an intermediate metabolite derived from thiamine, then it should be active in comparable concentrations to that of thiamine. It is conceivable that higher concentrations may be harmful.

3. The method of administering MHET has to be considered. If it is an intermediate metabolite, then frequent administration of small amounts is desirable. This was accomplished by mixing the MHET in the food.