676 6. ARSENICALS 



In a variety of organisms the utilization or oxidation of glucose has been 

 reported to be depressed 0-30% by arsenite at 1-10 mM (Eimhjellen and 

 Larsen, 1955; Fewster, 1956, 1958; Eeazin, 1956; Ramachandran and Wal- 

 ker, 1957; Litchfield and Ordal, 1958; Planterose, 1961; Ramachandran 

 and Gottlieb, 1963). (6) Stimulation of glucose utilization and glycolysis 

 has often been observed, and this probably arises from an inhibition of 

 pyruvate metabolism. This phenomenon will be discussed in some detail 

 and then we shall consider the effects of arsenite on the pattern of glucose 

 metabolism. 



If arsenite depresses the operation of the cycle, inhibits respiration, 

 and increases the ADP level, it might be expected to accelerate the utiliza- 

 tion of glucose by a Pasteur-like effect, providing arsenite does not signifi- 

 cantly inhibit the EM pathway directly and the 3-phosphoglyceraldehyde 

 step is limiting the rate. It is not sufficient to show that lactate formation 

 is increased, because this could result from the block of pyruvate oxidation, 

 but an increase in glucose disappearance or COg production can be taken as 

 evidence. A stimulation of fermentative COg formation aerobically by 

 arsenite was shown in yeast (Brady et al., 1961) and corn root tips (Beevers 

 and Gibbs, 1954). Arsenite is able to induce utilization of endogenous carbo- 

 hydrate in yeast both aerobically and anaerobically, even at as hiigh a 

 concentration as 66 mM; anaerobically the carbohydrate utilized is increased 

 from 323 to 800 //g/100 mg yeast, and simultaneously there are increases 

 in CO2 and ethanol formation (Brady et al, 1961). It appears from these 

 results that arsenite does not depress the EM pathway. The endogenous 

 glucose utilization by ox retina is elevated by 4 mM arsenite (Futterman 

 and Kinoshita, 1959), the utilization of glucose by guinea pig brain slices 

 is increased by 0.03 mAl arsenite (Takagaki et at, 1958), and the glucose 

 uptake by rat diaphragm is tripled by 1 mM arsenite (Randle and Smith, 

 1958). Although the mechanisms by which arsenite acts in these cases are 

 not well understood, it is clear that arsenite is not inhibitory to glucose 

 uptake or utilization. 



Further support for a differential effect of arsenite on the cycle and gly- 

 colysis is provided by the elevation of the R.Q. generally observed. In 

 yeast the R.Q. is increased from 1.04 to 1.41 by 0.5 mM arsenite and 

 to 2.13 by 5 mM arsenite (Pickett and Clifton, 1943), in pea stem sections 

 from 0.98 to 1.08 by 0.1 mM arsenite (Christiansen and Thimann, 1950 b), 

 in corn root tips from 1.08 to 1.81 by 1 mM arsenite and to 2.38 by 10 mM 

 arsenite (Beevers and Gibbs, 1954), in Ochromonas malhamensis from 1.10 

 to 1.32 by 2.5 mM arsenite (Reazin, 1956), and in carrot slices from 1.0 

 to 1.7 by 10 mM arsenite (Ap Rees and Beevers, 1960). These results are 

 probably to be interpreted as a suppression of the oxidation of glucose 

 simultaneously with little effect or a stimulation of glucose utilization. 

 The C-l/C-6 ratio appears to be increased, often very markedly, by arsenite: 



