786 6. ARSENICALS 



the presence of oxygen (Wieland and Franke, 1928), but more often is 

 probably enzymic. Spitzer (1898) showed that arsenite incubated with 

 liver extract at 37° for 18 hr is oxidized to the extent of 15%, but it is 

 impossible to say how much of this is nonenzymic. Similarly, arsenate incu- 

 bated with liver pulp or perfused through the liver is reduced to arsenite, 

 part of this probably being due to the glutathione content of the tissue 

 (Thuret, 1939). Blood with added glutathione also reduces arsenate. 

 The activation of tryparsamide has been associated since the work of 

 Levaditi and Yamanouichi (1908) with an unknown substance, sometimes 

 thought to be nonprotein (Yamanouichi, 1910) and sometimes protein 

 (Terry, 1912). Lourie et al. (1935) could not identify the substance respon- 

 sible for this reduction in blood but showed it to be in the erythrocytes 

 and not to be hemoglobin. It is evident that, in work with either the tri- 

 or pentavalent arsenicals, some consideration must be given to the possi- 

 bility of these reactions and effects due to the other member of the redox 

 pair. 



The clearest demonstration of the enzymic oxidation of arsenite has 

 come from Australia where cattle-dipping fluid was used as a source of 

 bacteria capable of oxidizing arsenite. Several species of bacteria were 

 found to oxidize arsenite at different rates, most requiring about 3 days to 

 oxidize 50% of the arsenite in a 20 mM solution at 25o (Turner, 1954). It 

 was calculated that 77 kcal/mole could be obtained from such an oxidation 

 but there is no evidence that this energy can be utilized by the cells. The 

 enzyme system responsible for this oxidation is adaptive, not making 

 itself evident unless the cells are grown in the presence of arsenite. The 

 organism most commonly investigated was Pseudomonas arsenoxydans- 

 quinque. A number of properties of this system were studied (Turner and 

 Legge, 1954): the time course of the oxidation is linear; the system is 

 substrate-saturated at about 0.9 mM, is well inhibited by cyanide, azide, 

 and carbon monoxide, and can utilize certain dyes as hydrogen acceptors. 

 A soluble cell-free preparation of this arsenite dehydrogenase was prepared 

 (Legge and Turner, 1954) and the effects of different inhibitors studied, 

 with odd results, in that several substances (pyrophosphate, phenylmercu- 

 ric nitrate, fluoride, iodoacetate, and thiourea) stimulate, while ^-mercuri- 

 benzoate inhibits rather weakly, and lewisite oxide has no effect. The 

 question of the cytochromes involved was studied (Legge, 1954), and it 

 was concluded that cytochrome c is not a carrier but can be reduced by 

 arsenite in the intact cell. It is possible that the rate of oxidation observed 

 in intact cells is due to the interaction of the dehydrogenase with the oxi- 

 dase without mediation of a carrier. It would be interesting to know some- 

 thing about the specificity of this enzyme and if it is truly an arsenite 

 dehydrogenase, as well as to determine if such occurs in other organisms 

 or tissues. 



