100 1. lODOACETATE AND lODOACETAMIDE 



where iodoacetate at I M completely blocks ATP synthesis from adenine 

 and inosine. 



Turning to studies in which the patterns of nucleotide change have been 

 recorded, a good deal of variability in response is noted (Table 1-15) as 

 might be expected on the basis of the different metabolic pathways for ATP 

 generation available in the organisms. The effects of iodoacetate in reducing 

 ATP and creatine-P levels are more marked under anaerobic than aerobic 

 conditions, and more marked in the presence of glucose than endogenously, 

 and occur faster if the tissue is functionally active. The rates of change of 

 these nucleotides following iodoacetate inhibition have seldom been measur- 

 ed, but in Chlorella (Fig. 1-7) and erythrocytes (Fig. 1-8) the changes with 

 time are quite as anticipated. The initial rise in ADP is probably common 

 and is due to the first reaction in the sequence ATP -^ ADP -^ AMP being 

 initially relatively fast (when ATP falls sufficiently the rate falls). 



The very marked metabolic difference between avian and mammalian 

 erythrocytes is nowhere better seen than in the response to iodoacetate 

 (Table 1-15). The essentially glycolytic ATP generation in human erythro- 

 cytes is readily inhibited by iodoacetate, whereas pigeon erythrocytes ap- 

 parently can maintain their ATP levels aerobically in the presence of glu- 

 cose by alternate pathways. The greater effects of iodoacetate on contract- 

 ing muscle point out the importance of functional activity in a tissue in 

 determining the response to inhibitors, and this must always be taken into 

 account in working with active tissues such as the heart or proliferating 

 organisms. When a frog muscle goes into contracture induced by bromo- 

 acetate, the pattern of the phosphate compounds changes markedly (see 

 accompanying tabulation) (Hermans, 1956). These changes not only are 



of significance in interpreting the secondary metabolic effects of iodo- 

 acetate, but also must be an important factor in the development of the 

 contracture. 



