88 1. lODOACETATE AND lODOACETAMIDE 



clear. Similarly, addition of lactate to iodoacetate-poisoned nerves reduces 

 the respiratory inhibition but never completely (see accompanying tabula- 

 tion) (Chang and Gerard, 1933), and in frog sartor ius lactate will also par- 



tially relieve iodoacetate inhibition, although succinate will not (Chang and 

 Yu, 1939). The respiratory CO2 of rat liver slices with trilaurin as substrate 

 is depressed 53% by 5 mM iodoacetate, but only 23% when pyruvate is 

 added (Geyer et a/., 1950 a), but this shows only that pyruvate can produce 

 some CO2 in the presence of iodoacetate. The respiration of beef kidney cell 

 suspensions is inhibited moderately by 1 mM iodoacetate and pyruvate does 

 not overcome this at all, which led Polatnick and Bachrach (1960) to con- 

 clude that the depression of the respiration is not caused by a lack of pyru- 

 vate arising from the EM pathway, this presumably meaning that iodoace- 

 tate acts elsewhere. Pyruvate also does not prevent the respiratory inhibi- 

 tion by iodoacetate in the fucalean alga Hormosira banksii, leading Bergquist 

 (1958) to propose that iodoacetate, even at 0.1 mM, acts on enzymes other 

 than 3-PGDH. On the other hand, acetate counteracts quite effectively the 

 depression of yeast respiration by 1 mM iodoacetate, so that Schmid (1958) 

 could assume a selective action on the EM pathway. The results from this 

 type of experiment are thus quite variable and there is much variation be- 

 tween tissues. 



Oxidation of Pyruvate, Lactate, and Acetate 



The incorporation of pyruvate into the cycle involves lipoate, coenzyme 

 A, and an SH-containing apodehydrogenase, so that some inhibition by 

 iodoacetate would be anticipated. Pyruvate oxidase preparations are indeed 

 inhibited (Table 1-13) but the data are inadequate to assess accurately the 

 sensitivity. One can conclude only that either the enzyme from different 

 sources is quite variable in its susceptibility to iodoacetate, or the different 

 experimental conditions used are responsible for the variable results. The 

 marked sensitivity of brain pyruvate oxidase observed by Peters and Wa- 

 kelin (1946) led them to place it between 3-PGDH and succinate dehydro- 



