624 3. DEHYDROACETATE 



of dehydroacetate; this will be discussed later (page 629), but Shideman 

 et al. (1950 b) do not think it is likely. The endogenous respiration in such 

 minces and slices is poorly understood, so that it is difficult to interpret 

 these results, and the data when glucose is present are inconsistent. It is 

 also difficult to relate these changes in respiration to inhibition of succinate 

 oxidase (the effects of malonate and dehydroacetate are quite different), 

 and such statements as "It appears probable that the manifestations of 

 toxicity result largely, if not exclusively, from a specific type of chemical 

 (or physicochemical) action involving interference with oxidative or other 

 enzyme mechanisms which proceed by way of the Krebs cycle" (Shideman 

 et al., 1950 b) appear to have little basis, particularly since the effects of 

 dehydroacetate on the operation of the cycle (as in mitochondrial prepara- 

 tions) have not been studied. It is significant that dehydroacetate at 4.7- 

 9.3 TaM stimulates the anaerobic glycolysis in rat brain mince 40-50% 

 (See vers et al., 1950), an effect greater than any observed on respiration. 

 On the other hand, 50 mM dehydroacetate inhibits the formation of C^^Og 

 from glucose-6-C^* 87% in suspensions of isolated thymus nuclei, simultane- 

 ously the O2 uptake being depressed only 14% and the ATP level falling 

 27% (McEwen et al, 1963 b). Malonate at 10 mM has very little effect and 

 this was attributed to a failure to penetrate into the nuclei; dehydroacetate 

 either penetrates better than malonate or exerts an effect other than inhi- 

 bition of succinate oxidation. 



EFFECTS ON TISSUE FUNCTIONS 



Dehydroacetate in the whole animal produces changes in central nervous 

 system, cardiovascular, and renal functions. Only the renal effects have been 

 investigated in detail. In addition, the actions on the isolated intestine have 

 been studied relative to the metabolic disturbances produced. 



Intestine 



The contractile amplitude of isolated rabbit intestine is depressed slightly 

 by 1 mM and markedly by 10 vclM dehydroacetate (see tabulation below) 



