TRICARBOXYLATE CYCLE 663 



one of the commonest pathways for pyruvate in the homofermentative 

 organisms, is not very sensitive (Walker, 1959). However, Reed et al. 

 (1958) found the dismutation of pyruvate by extracts of Streptococcus 

 faecalis to be reduced 70% by 0.1 mM arsenite, and the presence of lipoate 

 during the incubation not to alter the inhibition. Furthermore, in Aster o- 

 coccus mycoides the dismutation of pyruvate is depressed to about the same 

 extent as oxidation (Rodwell and Rodwell, 1954 a). Thus it would be wise 

 to withhold final judgment on the relative sensitivities of oxidation and 

 dismutation. The condensation of pyruvate to acetoacetate seems to be 

 well inhibited, but the condensation to acetylmethylcarbinol is more resis- 

 tant (Barron and Singer, 1945). Clostridium saccharobutyricum ferments 

 pyruvate to butyrate and acetate; in the presence of 1 raM arsenite, only 

 acetate if formed (Cohen-Bazire et al., 1948; Cohen-Bazire and Cohen, 

 1949). This might imply a block of the butyrate-forming cycle which occurs 

 in the Clostridia. The fermentation of pyruvate by Propionibacterium pen- 

 tosaceum is not aifected by even 40 mM arsenite (Wood and Werkman, 

 1940). The phosphoroclastic reaction, wherein formate and acetyl-P are 

 formed from pyruvate, is inhibited 50% by 0.01 mM arsenite in extracts 

 of Micrococcus lactilyticus (McCormick et al., 1962). The photometabolism 

 of pyruvate by RJiodospirillum rubrum is inhibited 80% by 1 mM arsenite 

 (Ormerd and Elsden, 1956). The anaerobic formation of hydrogen from 

 pyruvate by sheep rumen microorganism LC is reduced only 22% by 2.5 

 mM arsenite and 65% by 50 mM arsenite (Peel, 1960). In Aspergillus 

 terreus arsenite shifts the metabolism of pyruvate away from the formation 

 of itaconate and toward the synthesis of cell material (Bentley and Thies- 

 sen, 1957). In most cases these pathways for pyruvate are not understood 

 in detail, nor is it known if lipoate functions in these systems, but it seems 

 adequately demonstrated that arsenite can, especially in the microorgan- 

 isms, quite markedly alter the pattern of pyruvate utilization. 



The effects of arsenicals on acetate metabolism are less well understood 

 but it is evident from Table 6-4 that in most cases the utilization of acetate 

 is potently inhibited. The acetate-activating enzyme system and various 

 reactions forming or metabolizing acetyl-P or acetyl- AMP appear to involve 

 lipoate — indeed, acetyldihydrolipoate has been demonstrated, and thus 

 the site of the arsenical action could well be the free or bound lipoate. 

 Goldschmidt et al. (1956) studied the effects of arsenite on the metabolism 

 of labeled acetate in Penicillium but a concentration of 15 mM was used 

 so that little can be concluded from their results. The pattern of citrate 

 labeling is altered by arsenite, but this is undoubtedly due to effects on 

 the operation of the cycle rather than on reactions specific for acetate. The 

 inhibition of lactate metabolism by arsenicals is most likely attributable 

 to its utilization through pyruvate. Lactate dehydrogenase and other en- 

 zymes attacking lactate do not appear to be very sensitive. 



