462 THIAMINE 



As thiamine in the form of thiamine pyrophosphate is necessary for the 

 metaboHsm of pyruvate, one would expect that the amount of pyruvate 

 in lilood, and perhaps also in mine, may be increased in thiamine deficiency. 

 Platt^ and Piatt and Lu" indeed found a large increase of bisulfite-binding 

 substances, consisting mainly of pyruvic acid, in the blood of beriberi pa- 

 tients. Some hours after the administration of thiamine to the patients the 

 amount of the bisulfite binding substances dropped to normal. In animal 

 experiments Thompson and Johnson^ found that pigeons and rats with 

 symptoms of acute thiamine deficiency had a high blood pyruvate level. 

 One would be inclined to think that these symptoms of acute thiamine 

 deficiency might be caused by a pyruvate poisoning of the animal. The 

 work of de Jong,^ however, makes this supposition highly improbable. 

 De Jong devised a micromethod for determining the pyruvate level of a 

 small drop of blood; he thus was able to execute several determinations in 

 the course of the development of polyneuritis in the animals. In this way 

 he proved that the symptoms of acute polyneuritis in pigeons developed 

 before the rise of pyruvate, and the disappearance of the symptoms after 

 the thiamine administration preceded the return of the pyruvate level to 

 normal. 



The results of this work of de Jong seem to demonstrate that the poly- 

 neuritis signs are independent of the pyruvate metabolism and, for that 

 reason, of the catalytic action of thiamine pyrophosphate. 



From the work of Loewi and of Dale we know that a chemical substance, 

 the acetylcholine, plays a role in the transmission of nerve stimuli. 



Binet and Minz^ showed that the acetylcholine not only plays a role in 

 the transmission of the stimulus from the end of the nerve to the effective 

 organ but that it works also in the nerves themselves. The acetylcholine 

 content of the nerves was increased after electric stimulation. However the 

 addition of an extract of the non-stimulated nerve to that of the stimulated 

 nerve intensified the action of this extract, or of a solution of pure acetyl- 

 choline. This points to another substance present in the extract of the 

 stimulated nerve. The authors, considering that thiamine deficiency leads 

 to polyneuritis, assumed that the active substance of the stimulated nerve 

 might be this vitamin. So they compared the activity of the substance of 

 the stimulated nerve with that of thiamine. They found that their activities 

 in this respect were the same. They further showed that thiamine also 

 stimulates the activity of acetylcholine in the isolated intestine of the rat 



5 B. S. Piatt, Trans. Roy. Sac. Trap. Med. Hijg. 31, 493 (1938). 



6 B. S. Piatt and G. D. Lu, Biochem. J. 33, 1525 (1939). 



^ R. H. S. Thompson and J. R. Johnson, Biochem. J. 29, 694 (1935). 



8 S. de Jong, Arch, neerl. physiol. 21, 465 (1936). 



9 L. Binet and B. Minz, Cotnpt. rend. soc. biol. 117, 1027 (1934). 



