D. W. WOOLLEY 



thiamin — and these were the ones which synthesized thiamin — con- 

 tained an enzyme system which actively spHt pyrithiamin to yield 

 the pyrimidine portion, and, presumably, the pyridine fragment of 

 the molecule. 



Although it might seem that this pyrithiamin-splitting enzyme is 

 identical with that which synthesizes thiamin, this is probably not so. A 

 pyrithiamin-resistant strain of yeast developed in the laboratory by subculture 

 in the presence of the agent required thiamin as a growth factor. Therefore it 

 is possible to obtain an organism which can split pyrithiamin and yet cannot 

 synthesize thiamin. 



In this case, then, resistance in the thiamin-synthesizing forms 

 was correlated with the presence of a mechanism for destroying the 

 antagonist. The possession or lack of such a system for destruction 

 of the inhibitory analogue cannot be the universal answer to the 

 problem posed, because it has been shown that in the case of 3-acetyl- 

 pyridine, an analogue of nicotinic acid, the resistant organisms were 

 not able to destroy the substance. 



Another facet of the problem is the contrast between the action 

 of some metabolite analogues in microbial species and in animals. 

 Thus, thiopanic acid and the sulfonamides caused deficiencies of 

 pantothenic acid and of /?-aminobenzoic acid in bacteria, but were 

 innocuous in this respect in animals. On the other hand, 3-acetyl- 

 pyridine caused nicotinic acid deficiency in mice but not in bacteria. 

 Another nicotinic acid analogue, 3-pyridinesulfonic acid, was eff"ec- 

 tive in certain bacteria but not in mice. It may be that these phylal 

 dilTerences represent nothing more than variation in powers of excre- 

 tion, or it may be that they mirror various degrees of metabolism. 



One metabolite may be capable of participation in several 

 reactions, some of which may function in a given type of organism but 

 be absent from the metabolic network of others. If an inhibitor inter- 

 fered with the action of the metabolite in just one process, it would be 

 expected that it would be effective in only those species which utilized 

 this particular function of the metabolite. 



At about the same time that the facts discussed above were being 

 established, a second general type of biochemical antagonism was 

 being brought to light. This latter type dealt with proteins that were 

 antagonistic to vitamins by virtue of the ability of these proteins to 



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