ANEURINE (thiamine) 



This structure was confirmed by K. G. Stern and J. W. Hofer,^^ 

 who synthesised aneurine pyrophosphate by treating aneurine with 

 two molecular proportions or more of phosphorus oxychloride. Both 

 groups of workers found that the substance produced carbon dioxide 

 from pyruvic acid in the presence of yeast cells freed from natural 

 cocarboxylase. Enzymic methods of preparing cocarboxylase from 

 aneurine were subsequently described by H. Tauber,^^ by H. von 

 Euler and R. Vestin ^^ and by M. Silverman and C. H. Werkman,^^ 

 whilst an improved synthetic method was described by H. Weil- 

 Malherbe,32 j^ which the 5-bromoethyl-thiazole analogue of aneurine 

 hydrobromide was treated with silver pyrophosphate in pyrophos- 

 phoric acid solution at 100° C. for fifteen hours. The cocarboxylase 

 was isolated after conversion to the silver salt, precipitation with 

 phosphotungstic acid and recrystallisation from dilute alcohol. 



Phosphorylation of aneurine in vivo apparently takes place in the 

 upper part of the digestive tract, ^^ although attempts to convert 

 aneurine into cocarboxylase by incubation with juices from the 

 stomach, pancreas, duodenum or jejunum of dogs, or by mixtures of 

 the juices with mucosa extracts were unsuccessful. The reverse 

 change, however, that is, the hydrolysis of cocarboxylase to aneurine, 

 was readily effected by incubation with duodenal or jejunal juice. 

 The hydrolysis of aneurine monophosphate could also be effected by 

 phosphatase preparations, at a rate comparable with the hydrolysis 

 of cocarboxylase. H. Weil-Malherbe ^^ showed that neither aneurine 

 nor aneurine monophosphate functioned per se as coenzymes of car- 

 boxylase ; the latter has a longer induction period than the former, 

 presumably due to the fact that it must first be hydrolysed to free 

 aneurine. Aneurine could be converted into cocarboxylase by the 

 action of adenosine triphosphate. That aneurine monophosphate was 

 not an intermediate in the formation of cocarboxylase was confirmed 

 by the fact that, although it reduced the pyruvic acid content of the 

 blood of aneurine-deficient rats,^^ it had a somewhat lower activity 

 than aneurine itself. The conversion of aneurine into cocarboxylase 

 by adenosine triphosphate was confirmed by Elvehjem and his col- 

 leagues,^^ who also showed that cocarboxylase was formed from 

 aneurine in presence of washed dried yeast, hexose diphosphate and 

 boiled tissue extract. 



F. Lipmann ^7 reported that Lohmann's pure cocarboxylase 

 functioned as a coenzyme in the oxidation of pyruvic acid, and sug- 

 gested that aneurine was first converted into cocarboxylase which 

 then acted as the coenzyme of a system capable of catalysing the 

 liberation of carbon dioxide from pyruvic acid with formation of 

 either acetaldehyde or acetic acid. This theory was not at first 

 generally accepted, however, for R. A. Peters ^^ had found that pure 



94 



