122 1. lODOACETATE AND lODOACETAMIDE 



Wu (1959) pointed out that the metabolism of glycogen or glucose by 

 HeLa cells depends on the conditions of culture and other factors, so that 

 different steps may be limiting. This is probably true for all cells to varying 

 degrees since these metabolic pathways are capable of a great deal of flexi- 

 bility. The inhibition of glucose respiration in any particular cell or tissue 

 is likely to vary widely with not only the experimental conditions but the 

 past history. Examples are the greater sensitivity of the culture form com- 

 pared to the blood form of Trypanosoma rhodesiense, 0.033 mM iodoacetate 

 inhibiting the former 53% and the latter not at all (Ryley, 1962), and the 

 dependency of the inhibition of brain respiration on the age of the animals 

 (Tyler, 1942; Muir et al., 1959). The increasing sensitivity to malonate and 

 the decreasing sensitivity to iodoacetate with increasing age of rats indicate 

 that the metabolic patterns or controls are changing in the brain. 



Differential Effects on Glycolysis and Respiration 



Inspection of Tables 1-11, 1-17, and 1-18 shows that anaerobic glycolysis 

 is inhibited by iodoacetate to a much greater degree than respiration. 

 Lundsgaard (1930 c) in his initial work with yeast found that iodoacetate 

 at 1.1 mM inhibits fermentation completely without significant effect on 

 respiration over a period of an hour. This was termed the "Lundsgaard 

 effect" by Turner (1937), who gave a complete summary of the early work. 

 This differential effect was observed by a number of workers in all types 

 of organism and tissue, although most found only a "modified" Lundsgaard 

 effect in that respiration is depressed less or more slowly than glycolysis, 

 and some of these investigators suggested that glycolysis and respiration 

 are two entirely distinct metabolic phenomena. Such data seemed to argue 



