ACCUMULATION OF KETO ACIDS 673 



L-arabinose are unable in the presence of arsenite to metabolize any of the 

 pentonic acids, which are intermediates in the utilization of pentoses, and, 

 since this block is more potently exerted than the inhibition of keto acid 

 oxidation, no a-ketoglutarate can accumulate (Weimberg, 1961). In some 

 organisms glucose is partly oxidized and partly transformed into cell mate- 

 rial. Arsenite prevents pyruvate oxidation in Acetobacter xylinum but pyru- 

 vate does not accumulate since glucose is presumably diverted to form 

 cellulose, so that in this case one might say that arsenite has shifted the 

 pathway of glucose metabolism (Schramm et al., 1957). It is more difficult 

 to explain the results of Cantrell (1951, 1953) on trypanosomes taken from 

 rats treated with oxophenarsine, since glucose utilization was not signifi- 

 cantly altered while less pyruvate was formed than in untreated trypano- 

 somes. However, since untreated organisms formed 1.7 moles of pyruvate 

 from each mole of glucose, it is evident that this trypanosome is unable 

 to metabolize pyruvate readily, and thus the only effect noted would be 

 a small depression in the rate of pyruvate formation, possibly certain gly- 

 colytic intermediates accumulating. 



It is interesting to inquire whether arsenicals can ever allow a quantita- 

 tive conversion of a substrate into a keto acid. Eimhjellen and Larsen 

 (1955) performed a balance study on Aspergillus terreus with glucose as 

 the substrate and found that 75% of the glucose accumulates as pyruvate 

 and 20% as acetaldehyde in the presence of 10 mM arsenite, which is 

 near-complete recovery. In the absence of arsenite, no pyruvate or acetal- 

 dehyde is detectable. Pseudompnas saccharophila converts each mole of 

 glucose to around 1.7 moles of pyruvate in the presence of 2 mM arsenite 

 (Entner and Doudoroff, 1952), and very similar results have been obtained 

 with Serratia marcescefis, an additional 0;6 mole being found in the form of 

 a-ketogluconate, this corresponding to 95% recovery (Wasserman and 

 Hopkins, 1958). The alga Ochromonas malhamensis almost completely oxi- 

 dizes glucose, no lactate or pyruvate and very little ethanol being found, 

 but, in the presence of 2.5 n\M arsenite, 85% of the glucose in converted to 

 these products (Reazin, 1956). Finally, in ox retina endogenous glucose and 

 lactate are aerobically 34% converted to pyruvate, whereas with 4 mM 

 arsenite the conversion is 65% (Futterman and Kinoshita, 1959). From 

 these results it seems quite possible that, under the proper conditions and 

 with the correct arsenical concentration, quantitative formation of pyru- 

 vate, and any substances arising directly from pyruvate, might be achieved. 



Keto acids also accumulate in animals poisoned with arsenite. Oelkers 

 and Vincke (1936) originally observed this in rabbits given 3 mg/kg potas- 

 sium arsenite and then injected with oxalacetate 3 min later, both oxala- 

 cetate and pyruvate appearing in the urine whereas in normal animals 

 the oxalacetate is completely metabolized. El Hawary and Thompson 

 (1954) found blood pyruvate to rise about 5-fold in rats administered arsen- 



