Specific Inhibition of Thiamin Utilization

Buchman, Heegard, and Bonner (48) observed a very interesting inhibition of the activity of a carboxylase system by the pyrophosphate of the vitamin thiazole (4-methyl-5-/3-hydroxyethyl-thiazole pyrophosphate). This inhibition was explained as due to a competition between cocarboxylase (thiamin pyrophosphate) and the thiazole pyrophosphate, for the carboxylase protein, the thiazole pyrophosphate giving an inactive enzyme analogue. On the other hand, Niven and Smiley (272a) found that co-carboxylase was 40% more active than intact thiamin for Streptococcus salivarius. (See also Sarett and Cheldelin, addl. ref., 325a). 

Inhibitory Power of Pyrithiamin for Various Micro-organisms Correlated with Requirement of Thiamin as Growth Factor (4SS) 

Inhibition index g. pyrithiamin required to reduce to ) maximal, growth promoted by 0.01 ug- thiamin/ml. medium, in case of those organisms which require thiamin. For those organisms which did not require added thiamin, the media contained none added and could not have contained 0.001 /tS-/ml. (by assay). This figure was taken in calculating the inhibition index. 

Organism Inhibition index pyrithUmin/thiunin Tbiunin requirement of the organism 

The exact mode of action of pyrithiamin is thus still obscure what is clear is that it must be closely concerned with interference ivith thiamin function, and this inhibition is due to structural similarity with the essential metabolite with which it interferes. 

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