656 6. ARSENICALS 



tivities of the a-keto acid oxidases and succinate dehydrogenase for the 

 reason that the sensitivities of each type of enzyme vary from species to 

 species or tissue to tissue, as reference to Table 6-3 will show. Furthermore, 

 the particular arsenical used determines to some extent the ability to in- 

 hibit selectively. It would probably be exceptional to have conditions 

 under which an arsenical at any concentration is able to inhibit a-keto 

 acid oxidation over 90% without affecting succinate oxidation, but from 

 the results reported it might be possible, e. g., in pigeon brain. One must 

 examine the situation in the preparation being studied and preferably 

 determine concentration-inhibition curves for the different enzymes in 

 mitochondrial suspensions. In any case, both of these effects would reduce 

 cycle activity and, in those instances in which both types of enzyme are 

 well inhibited, the final result might well be a more selective block of the 

 cycle relative to other metabolic pathways. On the other hand, the disub- 

 stituted arsenicals, such as diphenylchloroarsine, would be expected to 

 block the cycle at the aconitase and isocitrate dehydrogenase steps, and 

 simultaneously, to inhibit creatine kinase to approximately the same degree 

 but there has been no work on this point. It could be that these arsenicals 

 under certain conditions block the transfer of high-energy phosphate 

 between creatine and ADP selectively, especially if the cycle were not in- 

 volved, as under anaerobic conditions, but insufficient data are available 

 on the spectrum of action of these disubstituted arsenicals. 



A large number of enzymes have been omitted from Table 6-3. We may 

 note that the following enzymes are not inhibited by arsenite at the con- 

 centrations (niM) given in parentheses: acetylenecarboxylate hydrase (1), 

 adenosine-5'-phosphosulfate reductase (1), asparaginase (4), catechol 

 oxygenase (1), cholesterol dehydrogenase (50), citrullinase (1.7), DDT 

 dehydrochlorinase (1), dihydrofolate reductase (10), dihydroorotate dehy- 

 drogenase (10), ergothionase (1), formyltetrahydrofolate synthetase (100), 

 fructose-6-P phosphoketolase (10), galactonolactone dehydrogenase (1), 

 glutamine synthetase (12), glutaric semialdehyde dehydrogenase (0.33), 

 glyoxylate reductase (5), 3-hydroxyanthranilate oxidase (1), imidazole- 

 iV-methyl transferase (1), a-ketoisocaproate decarboxylase (5), 4-keto- 

 proline reductase (0.1), D-lactate oxidase (10), 5,10-methylenetetrahydro- 

 folate dehydrogenase (1), nitrate reductase (20), nucleotidase (33), orni- 

 thine carbamyl transferase (10), oxalate decarboxylase (1), oxalate oxidase 

 (5), phenylalanine 4-hydroxylase (5), porphobilinogen isomerase (1), 

 streptococcal proteinase (10), steroid dehydrogenase (1), thiogalactoside 

 transacetylase (5), transketolase (0.1), and D-xylose reductase (10). 



