426 THIAMINE 



food intake is reduced to a low level. After they receive a small fraction of a 

 milligram of thiamine, however, their appetite is restored at once and their 

 weight increases enormously. This led to the supposition that the vitamin 

 has something to do with cell metabolism. Several workers investigated the 

 influence of thiamine on the metabolic rate of tissues. 



Westenbrink^ has reviewed all the investigations published between 1920 

 and 1932 and has analyzed the data from fifteen publications on this sub- 

 ject. About half the workers give a positive, and the other half a negative, 

 answer. However, after statistically evaluating the work, Westenbrink 

 found that in only two of the fifteen investigations the metabolism of vita- 

 min-rich tissues was significantly higher than in \itamin-poor ones. He 

 himself could find no difference.^ The definite answer to this question came 

 from the brilliant work of Peters and his school in Oxford. Peters realized 

 that the development of opisthotonus, which is a sign of the last stages of 

 polyneuritis in pigeons and fowls, proved that the disorder in thiamine- 

 deficient animals affects both the peripheral and the central nervous system. 

 In 1929 Peters and Kinnersley investigated the metabolism of polyneuritic 

 pigeons; the only abnormality they could find was a slight increase in the 

 amount of lactic acid in the brain of pigeons in opisthotonus. Peters also 

 studied the oxygen uptake by minced brain from pigeons in opisthotonus 

 in comparison with that of normal birds. The great difference from many 

 of his predecessors was that he added lactic acid (Kinnersley and Peters^) 

 or in later experiments sugar or pyru\'ic acid to the brain (Peters and Sin- 

 clair,^ Peters and Thompson,^ Thompson,^ and Peters''). In a long series of 

 experiments Peters demonstrated that thiamine plays a decisive part in 

 carbohydrate, and especially in pyruvic acid, metabolism. Peters definitely 

 established the fact that the metabolism of brain from polyneuritic pigeons, 

 as measured by oxygen uptake in Barcroft-Warburg tubes, w^as less than 

 that of the brain of normal pigeons. Furthermore, Peters demonstrated that 

 the addition of a solution of thiamine to minced brain from polyneuritic 

 pigeons suspended in pyruvic acid solution increased the oxygen uptake 

 of this mixture (catatorulin effect of thiamine). This was the first instance 

 of a chemical substance catalyzing an organ tissue preparation (Passmore 

 et at}). The work of the Oxford school was confirmed by Sherman and 

 Elvehjem.' Further research led to the concept that the catalysis affecting 



1 H. G. K. Westenbrink, Arch. need, physiol. 17, 239 (1932). 



2 H. G. K. Westenbrink, Arch, neerl. physiol. 17, 549 (1932). 



3 H. W. Kinnerslejr and R. A. Peters, Biochem. J. 24, 711 (1930). 



4 R. A. Peters and H. M. Sinclair, Biochem. J. 27, 1910 (1933). 



6 R. A. Peters and R. H. S. Thompson, Biochem. J. 28, 916 (1934). 

 « R. H. S. Thompson, Biochem. J. 28, 909 (1934). 

 7R. A. Peters, Biochem. J. 30, 2206 (1936). 



8 R. Passmore, R. A. Peters, and H. M. Sinclair, Biochem. J. 27, 842 (1933). 



9 W. C. Sherman and C. A. Elvehjem, Am. J. Physiol. 117, 142 (1936). 



