EFFECTS OF PH ON ARSENICAL INHIBITION 775 



interesting way but has been concerned primarily with the occurrence of 

 skin, lung, and liver tumors in Moselle vintners, who for many years in- 

 gested quite large amounts of arsenic in their wines (a mean of 57.3 g 

 over a 12 -year period). 



EFFECTS OF pH ON ARSENICAL INHIBITION 



The actions of the arsenicals may be modified by many factors and most 

 of these have been discussed in previous sections, e. g., the effects of enzyme 

 purity, O2 tension, thyroid, tocopherol, and thiamine deficiency on the 

 respiratory and glycolytic responses, and of temperature. The effects of 

 pH on the inhibition of enzymes by the arsenicals were also summarized 

 (page 649) and thus the only major topic left to be discussed is the pH 

 factor in cellular systems. The modifications of arsenite ui)take in Valonia 

 and flesh fly larvae by pH have been mentioned previously (page 699). 



The inhibition of yeast respiration by 1 mM phenylarsenoxide is mod- 

 ified by pH (see accompanying tabulation) and it was claimed that these 



results are in harmonj^ with the amphoteric character of this arsenical 

 (Voegtlin et al., 1931). It is difficult to see how phenylarsenoxide could 

 be considered as amphoteric in this range of pH, and equally difficult to 

 understand why the inhibition would increase at ijH 7.84, even if an anion 

 is being formed, unless the reaction is at the cell surface and penetration 

 is unnecessary. The inhibition of yeast fermentation by arsenite is not 

 altered between pH 3 and 6, but is moderately reduced above pH 7, which 

 is possibly related to the ionization of arsenious acid (Brady et al., 1961). 

 There is little if any change in the keto acid accumulation in Microsporum 

 audouini induced by arsenite over the pH range 5.4-8 (Chattaway et al, 

 1956). The results on these organisms thus imply that the pH is a rather 

 unimportant factor in arsenical action and this is what would be expected. 

 A very thorough study of the effects of pH on the trypanocidal action 

 of the acidic phenylarsenoxides was made bj^ Eagle (1945), wherein show- 

 ing the trypanocidal activity to be strongly dependent on the pH in 

 the manner expected if penetration into the cells involves the un-ionized 

 forms. As the pH is lowered from 8.4 to 5.65, a 10- to 100-fold increase of 



