Inhibition of Carboxylase by Thiazole Pyrophosphate

Abstract

In the course of investigations dealing with vitamin B1 (thiamin) analogs, and having as their goal the furtherance of our knowledge of the physiological rôle of the vitamin, we have observed that a number of substances having a structure similar to that of cocarboxylase (thiamin pyrophosphate [1]), although not themselves able to replace the latter in the enzymatic decarboxylation of pyruvic acid, are able to inhibit markedly the activity of the carboxylase system. The most active inhibitant studied is the pyrophosphoric acid ester of the thiamin thiazole moiety (the thiazole pyrophosphate portion of the cocarboxylase molecule), which will be referred to as "thiazole pyrophosphate."

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