674 6. ARSENICALS 



ite subcutaneously, and El Hawary (1955) detected a similar rise in a-keto- 

 glutarate. Some elevation of the acetone and acetoacetate levels also occurs, 

 as would be expected if the operation of the cycle is impaired. A depression 

 of pyruvate utilization by the arsenite was also shown by the higher blood 

 pyruvate levels following intravenous injection of pyruvate; in normal 

 animals after 30 min the blood pyr 

 nite-treated rats it was 10 mg%. 



GLUCOSE METABOLISM 



The utilization of glucose may be affected by the arsenicals either directly 

 of indirectly. We are thus concerned primarily with (a) the actions of the 

 arsenicals on the EM and pentose-P pathways, and (b) the occurrence of 

 a Pasteur-like effect to accelerate glucose uptake. It is further of interest 

 to determine the differential effects of the arsenicals on pre- and post- 

 pyruvate metabolism. It must be emphasized that the results on the re- 

 sponses of glucose metabolism to the arsenicals have varied a good deal 

 and have often been so divergent as to be beyond reasonable explanation. 

 Some results on anaerobic glycolysis are presented in Table 6-6, but in 

 most instances CO2 formation was measured so that the results perhaps 

 do not always indicate the actual effect on lactate or ethanol production. 

 It is unfortunate that the organic arsenicals have not been examined in 

 greater detail. Despite some of the data in the table, it appears that the 

 EM pathway is not particularly sensitive to arsenite. Some of the evidence 

 for this may be summarized. (1) Arsenite often produces an accumulation 

 of pyruvate with glucose as the substrate, as discussed in the previous sec- 

 tion, indicating that the formation of pyruvate from glucose is a good deal 

 less sensitive than the utilization of pyruvate. (2) None of the enzymes of 

 the EM pathway has been found to be particularly susceptible to the arsen- 

 icals (Table 6-3). (3) The distal portion of the EM pathway between 3-phos- 

 phoglyceraldehyde and pyruvate has been found to be resistant to arsenite. 

 Thus Mortenson et al. (1955) noted that 3-phosphoglyceraldehyde is con- 

 verted readily to pyruvate by extracts of Azotobacter vinelandii in the pre- 

 sence of 10 mM arsenite, and White and Wang (1964) showed that 3-phos- 

 phoglycerate forms pyruvate in extracts of Acetobacter xylinum with 

 5 mM arsenite, although some inhibition occurs when the system is supple- 

 mented with ADP. (4) Almost complete inhibition of glucose respiration 

 without effect on anaerobic glycolysis has been observed in Jensen sarcoma 

 (Dresel, 1926) and rabbit blood (Coxon and Robinson, 1956). In the latter 

 instance, 0^*0^ from labeled pyruvate is reduced 91% by 1 *mM arsenite, 

 while that from labeled glucose is unaffected. (5) A number of studies 

 have demonstrated that the aerobic utilization of glucose is not affected 

 or only moderately affected by arsenite at concentrations of 1 mM or above. 



