690 6. ARSENICALS 



bolism by inhibiting lipases, since these enzymes are sensitive in some in- 

 stances, particularly to atoxjd (Table 6-3). The extremely potent inhibi- 

 tions reported by Rona and his collaborators have not been confirmed by 

 other investigators, and it is very unlikely that the arsenicals at the con- 

 centrations occurring in the tissues during poisoning exert an appreciable 

 effect on lipid metabolism through this mechanism. However, histochemical 

 studies must be done to settle this point. 



Both the synthesis and oxidation of fatty acids are readily inhibited 

 by the arsenicals. The incorporation of acetate into fatty acids by a solu- 

 ble system from pigeon liver is completely blocked by 0.1 mM arsenite 

 (Brady et al., 1956), but is much more resistant in chloroplasts, only 25% 

 depression being observed with 0.5 vciM (Mudd and McManus, 1964). 

 Potent inhibition of synthesizing systems from rat liver (Brady et al., 

 1960) and pigeon liver (Bressler and Wakil, 1962) requires the addition of 

 a monothiol, such as mercaptoethanol, and this with the high sensitivity 

 to arsenicals has led Brady (1960) to postulate the presence of vicinal SH 

 groups, although these appear not to be lipoate which is present in insignif- 

 icant amounts in the pigeon liver preparation. The condensation of acetyl- 

 CoA (or butyryl-CoA) with malonyl-CoA is not markedly inhibited so that 

 the dithiol group may function in the subsequent reductive reaction. Turn- 

 ing to the oxidation of fatty acids, one finds that the conversion of hexanoate 

 and zl^-hexenoate to acetoacetate by rat liver homogenate (Witter et al., 

 1950), and the oxidation of palmitate by a particulate fraction from peanut 

 cotyledons (Humphreys et al., 1954), are strongly depressed by arsenite, 

 the latter completely by 0.1 mM. Pea stem sections incubated with auxin 

 convert fats into sugars, and 0.1 mM arsenite — at which concentration 

 growth is depressed 50% — inhibits this around 90% (Christiansen and 

 Thimann, 1950 b). The sites of inhibition and the effects of the arsenicals 

 on the various enzymes of the fatty acid oxidation helix are unknown. 

 It is thus clear that both the formation and utilization of the long-chain 

 fatty acids are very sensitive to the arsenicals. On the other hand, the oxi- 

 dation of butyrate, at least by locust thorax particles, is relatively unaffected 

 (Meyer et al., 1960). Although utilization of acetoacetate by guinea pig 

 kidney slices is fairly strongly inhibited by arsenite (Quastel and Wheatley, 

 1935), the synthesis of acetoacetate from acetyl-P in the presence of 

 coenzyme A, phosphotransacetylase, and thiolase is only weakly inhibited 

 (Drummond and Stern, 1960), but the conversion of pyruvate to acetoace- 

 tate would probably be readily blocked. Inasmuch as all the reactions form- 

 ing or utilizing acetyl-CoA in the accompanying diagram are quite potently 

 inhibited by the arsenicals, it is difficult to predict what would happen to 

 the fatty acid levels, particularly in vivo. The relative degrees of inhibition 

 exerted on these four reactions by a chosen concentration of arsenical would 

 determine the over-aU effect, and this would undoubtedly change with 



