ANEURINE (thiamine) 



no vitamin B^ activity, but was toxic to mice and rats, causing a 

 decline in weight and a drop in food intake ; unlike neopyrithiamine, 

 it did not produce polyneuritic symptoms in rats.^^ It was a potent 

 antagonist of aneurine, however, and increased the levels of pyruvic 

 and lactic acids in the blood of rats and the pyruvate : lactate ratio. ^^ 

 It increased the urinary excretion of aneurine, presumably because it 

 displaced aneurine from the tissues,'*^ and it inhibited the action of 

 thiaminase on aneurine.*^ It produced typical symptoms of vitamin 

 Bi deficiency in chicks. ^^ Because of its anti-vitamin B^ activity, it 

 was tested in poliomyelitis (see page 51), but was found to protect 

 mice less effectively than did a vitamin B^-free diet.** 



Other Antagonists 



Von Euler et al.^^ claimed that salicylic acid and certain other 

 acids inhibited the action of some enzyme systems, including the 

 " aetiozymase " system, that is, the decarboxylation of pyruvic acid 

 in presence of added cocarboxylase. The effect was said to be en- 

 hanced by acetaldehyde, which is itself an inhibitor. The extent of 

 the inhibition by salicylic acid did not increase in proportion to the 

 reduction in the cocarboxylase concentration. The evidence, it was 

 suggested, indicated that salicylic acid and other inhibitors acted by 

 displacing coenzymes from attachment to the apoenzjone molecule or 

 by attaching themselves to a group in the apoenzjone molecule not 

 already occupied by the coenzyme. This suggestion is actually 

 another way of enunciating the Woods-Fildes hypothesis (see page 

 546), which satisfactorily explains the behaviour of pairs of inhibitors 

 and growth factors, such as sulphanilamide and ^-aminobenzoic acid, 

 pantoyltaurine and pantothenic acid, pyridine-^-sulphonic acid and 

 nicotinic acid, pyrithiamine and aneurine. 



The Woods-Fildes hypothesis demands a high degree of specificity 

 between these pairs of substances, based on analogous chemical 

 structure, and it is irrational to apply the hypothesis to a heterogeneous 

 group of inhibitors such as that listed by von Euler et al. If the 

 effect noted really exists it can hardly be due to a competition between 

 inhibitor and coenzyme in the sense in which Woods and Fildes used 

 this conception, but rather to a non-specific type of poisoning. 



The only true analogue of aneurine other than pyrithiamine, neo- 

 pyrithiamine and oxythiamine that appears to antagonise completely 

 the growth-promoting action of the vitamin is the «-butyl homologue, 

 which was shown ^^ to produce aneurine deficiency in rats maintained 

 on a suboptimal intake of aneurine ; the symptoms were relieved by 

 administration of aneurine. 



Attempts to find simple derivatives of thiazole that would inhibit 



128 



