RESPIRATION 677 



from 1.70 to 9.96 in Streptomyces olivaceus by 1 mM arsenite (Maitra and 

 Roy, 1959), from 0.85 to 1.61 in carrot slices by 10 mM arsenite (Ap Rees 

 and Beevers, 1960), and from 1.11 to 25 in guinea pig brain slices by 0.2 

 mM arsenite (Hoskin, 1960 b). This is a reflection of the relatively greater 

 inhibition of pyruvate oxidation compared to glucose metabolism and does 

 not necessarily imply the operation of the pentose-P pathway, although 

 the increase in pyruvate might be expected to favor the pentose-P pathway 

 by oxidizing NADPH. There is no evidence that arsenite inhibits the pen- 

 tose-P pathway or the Entner-Doudoroff pathway (Lewis et al., 1955; 

 Katznelson, 1958). For example, the conversion of 6-phosphogluconate via 

 3-phopshoglyceraldehyde to pyruvate in extracts of Acetohacter does not 

 seem to be significantly altered by 2 mM arsenite. Usually the formation 

 of C^^Oa from glucose- 1-C^^ is not inhibited by arsenite, even at 5 mM 

 in the case of Serratia marcesceyis (Wasserman and Hopkins, 1958), but 

 in brain slices 0.2 mM arsenite reduces it about 50% (Hoskin, 1960 b). 

 The shift in the pattern of glucose metabolism brought about by arsenite 

 both aerobically and anaerobically is well illustrated in the balance studies 

 of Stickland (1956 b), in which the divergence of glucose from oxidative 

 to fermentative pathways in yeast is evident, the total amount of glucose 

 used not being greatly altered. 



The effects of the arsenicals on carbohydrate metabolism are complex 

 and it is impossible to predict the over-all response without knowing in 

 detail the metabolic pathways and their controls in the particular tissue. 

 Even though the arsenical selectively blocks pyruvate oxidation, the changes 

 in glucose uptake, respiration, polysaccharide synthesis, COg production, 

 and lactate concentration will be variable in different situations because 

 they depend on what pathways are available, the relative activities of these 

 pathways, the metabolic controls which may be operative, and the functional 

 or metabolic state of the preparation. It is quite conceivable that the 

 effects of an arsenical would be quite different in an actively functioning 

 tissue compared to a resting tissue, due for one thing to the different de- 

 mands for ATP; thus in a resting tissue arsenite might accelerate glucose 

 uptake by a moderate rise in the ADP level, whereas in an active tissue the 

 ATP might fall so low that phosphorylation of glucose might be impaired. 

 One must also bear in mind the possible indirect effects of arsenicals medi- 

 ated by actions on the growth or functional aspects of the cells. 



RESPIRATION 



Cellular respiration is inhibited by the arsenicals, as one would expect 

 if cycle activity is impaired, but the effects are often less than would be 

 predicted on the basis of the sensitivity of the keto acid oxidases. The re- 

 sults in Table 6-7 were selected to illustrate certain characteristics of arsen- 



