Enzymes 59 



pounds containing one -SH group) . On the other hand, the re- 

 action of lewisite with the monothiol glutathione could be pre- 

 vented by other simple monothiols. These results suggested that 

 the major toxic action of lewisite was due to its action on the 

 pyruvic oxidase system and that the reactive component in this 

 enzyme system was a dithiol. In fact, the di-thiol compound, lipoic 

 acid is a coenzyme for the oxidative decarboxylation of pyruvate. 

 Inactivation of this coenzyme is therefore likely to be the mechan- 

 ism of the lethal action of lewisite. The other effects of these 

 chemical warfare compounds, vesication and mitotic inhibition in 

 dividing cells, are less plausibly explained. 



DEFICIENCY STATES AND RESPIRATORY ENZYMES 



(See also Sebrell and Harris, 1955) 



Thiamine 



Thiamine is a constituent of the vitamin B complex, deficiency 

 of which in the diet leads to Beri-Beri. Brain tissue from pigeons 

 fed on a thiamine-deficient diet shows a deficient power to oxidise 

 pyruvate. This failure is not due to lack of the appropriate enzyme 

 but to deficiency of thiamine pyrophosphate which is a coenzyme 

 required for the decarboxylation of pyruvate, a reaction which is 

 a necessary prelude to the formation of acetyl CoA (Fig. 6) . Thus 

 once again blockage of a single stage in the tricarboxylic acid cycle 

 brings respiration and energy production to a stop. An interesting 

 variant of thiamine deficiency is provided by a lethal disease of 

 foxes known as Chastek paralysis. This condition is due to thiamine 

 deficiency induced not by lack of thiamine in the diet but by the 

 enzymic destruction of thiamine due to the presence of thiaminase 

 in raw fish fed to the animals at certain times of the year (Krampitz 

 and Woolley, 1944) . 



Nicotinic Acid 



This substance is also a member of the vitamin B complex and 

 deficiency in man results in pellagra. Nicotinic acid is a component 

 of the pyridine nucleotides DPX and TPN which act as hydrogen 

 carriers in cell respiration and glycolysis (Figs. 3 and 6) , and which 

 are essential for energy generation. Lack of nicotinic acid in the 



