TRICARBOXYLATE CYCLE 95 



achieve a reasonably selective block of the EM pathway. It may be noted 

 that the respiration of unstimulated slices with either glucose or lactate is 

 not appreciably affected by iodoacetate up to 0.1 mM. 



The only thorough study of the effects of iodoacetate on the cycle in iso- 

 lated mitochondria is that of Yang (1957). Rat heart mitochondria were in- 

 cubated with the inhibitors for 10 min and the respiration measured over 

 1 hr after adding the various substrates (Table 1-14). There is a very sub- 



Table 1-14 

 Inhibition of Rat Heart Mitochondrial Oxidations by Iodoacetate and 



lODOACETAMIDE" 



« From Yang (1957). 



stantial inhibition of pyruvate oxidation by 0.1 mM iodoacetate, but only 

 slight effects at 0.01 mM. Iodoacetate at 1 mM suppresses all oxidations 

 quite strongly. Although the cycle is not as readily inhibited as the EM 

 pathway, such results should deter investigators from glibly terming iodo- 

 acetate a specific inhibitor of glycolysis, especially after using concentra- 

 tions of 1 mM or over. 



The effects of iodoacetate on the oxidation of acetate also afford evidence 

 for the inhibition spectrum. In Pseudomonas calco-acetica proliferating aer- 

 obically in an acetate medium, some of the acetate is assimilated into cell 

 material and some is oxidized. Iodoacetate above 0.0125 mM begins to 

 reduce the rate of oxidation, but at 0.014-0.1 mM increases the fraction 

 of the acetate oxidized; i.e., it inhibits assimilation more than oxidation 

 (Clifton, 1937). The oxidation of acetate by Corynebacterium creatinovorans 

 (Singer and Barron, 1945) and Acetobacter peroxidmis (Tanenbaum, 1955) 

 is inhibited over 90% by 5 mM iodoacetamide and 0.5 niM iodoacetate, 

 respectively. Iodoacetate at 1 mM blocks fermentation and glucose respira- 



