666 



6. ARSENICALS 



It is interesting that arsenite is able to depress the oxidations of pyruvate 

 and acetate in vivo. When arsenite is administered intraperitoneally at 

 a dose of 5 mg/kg/day for 3-4 weeks, rats suffer some toxic effects but are 

 not killed, and their tissues exhibit impaired metabolism (see accom- 

 panying tabulation) (Mookerjea and Sadhu, 1955). It is not known whether 



there is a direct effect on succinate oxidation of whether this small inhibi- 

 tion observed reflects inhibition of a later step. It is rather remarkable 

 that inhibitions of this degree can exist in the tissues of living animals and 

 one would like to know more of the metabolic patterns in these poisoned 

 animals. It may also be noted that when lewisite is applied to the skin 

 of rats at a dose of 45-95 //g/g skin, the oxidation of pyruvate is inhibited 

 58% while the oxidation of succinate is scarcely altered, and doses of 

 125-160 //g/g completely block pyruvate oxidation (Thompson, 1946). 

 The oxidations of the cycle intermediates are inhibited to varying de- 

 grees by the arsenicals. Comparative studies are uncommon (see accompa- 

 nying tabulation). Arsenite was 1 mikf in both cases. Essentially the same 

 relative susceptibilities are seen for avocado (Avron and Biale, 1957) and 

 the fungus (J. G. H. Wessels, 1959). The difference in the patterns of inhi- 

 bition by mono- and disubstituted arsenicals is well illustrated in the results 



