672 6. ARSENICALS 



and maltose (11-24), little with galactose or lactose (3-5), and none from 

 sucrose, lactate, succinate, or citrate in Microsporum canis in the presence 

 of 5 mM arsenite. 



The presence of arsenical-resistant pathways for the metabolism of the 

 keto acids will reduce the degree of accumulation. Microorganisms especially 

 frequently possess means of metabolizing pyruvate through reactions 

 less sensitive than pyruvate oxidase to the arsenicals, and here some of the 

 products of these pathways may accumulate rather than pyruvate. Some 

 of the pyruvate will be reduced to lactate in most preparations, and the 

 transamination of the keto acids to amino acids will often suppress their 

 accumulation. Thus amino acids occasionally accumulate, as shown in 

 Aerobacter aerogenes (Fowler and Werkman, 1955) and Brucella abortus 

 (Altenbern and Housewright, 1951). Such losses of the keto acids may be 

 very significant in balance studies. It is interesting in retrospect to consider 

 the early observations of increased lactate following arsenite. Meyer (1881) 

 reported that administration of arsenite to rabbits led to the appearance 

 of some acid in the blood, and Araki (1893) and Heffter (1893) established 

 that lactate does indeed appear in the urine and the muscles during poi- 

 soning. Morishima (1900 b) extended these observations to show that lac- 

 tate also appears in the liver, kidney, and gastrointestinal tract. Accumu- 

 lation of lactate has more recently been demonstrated in fibroblast cultures 

 (Meier, 1933) and in homogenates of mammary gland and brain (Terner, 

 1954). It is likely that the lactate arises from pyruvate which cannot be 

 oxidized, but originally it was thought that arsenite stimulated glycolysis 

 (which is true if glycolysis is defined as the formation of lactate, but false 

 if this is interpreted as an acceleration of the reactions leading to lactate). 

 It may be noted that a Pasteur-like effect can occasionally be exerted by 

 arsenite (see page 676). 



In some instances the results with the arsenicals do not conform to the 

 classical picture, due presumably to the special metabolic pathways present. 

 Beevers and Gibbs (1954) tried to find the concentration of arsenite which 

 would inhibit respiration and allow the accumulation of pyruvate in corn 

 root tips, but found instead that ethanol and acetaldehyde accumulate, 

 this being interpreted as a stimulation of aerobic fermentation. Xanthine 

 is metabolized to pyruvate by Clostridium acidi-urici by a pathway which 

 may be represented as 



Xanthine ->■ formate + glycine ->■ serine -> pyruvate 



(Sagers and Beck, 1956). Here arsenite actually prevents the appearance 

 of pyruvate and causes the accumulation of formate and glycine, it being 

 in this case more inhibitory to the reaction forming serine than to pyruvate 

 utilization. Pseudomonas fragi grown with D-arabinose responds normally 

 to arsenite in that or-ketoglutarate accumulates, but cells grown with 



