ANAEROBIC GLYCOLYSIS AND FERMENTATIONS 



79 



sensitive to iodoacetate (Gerlach and Liibben, 1959), but some accumula- 

 tion of triose-P and hexose phosphates occurs with 0.25 mM bromoacetate 

 (Dische and Ashwell, 1955). 



The results on the accumulation of intermediates do not establish con- 

 clusively that the sole site of iodoacetate action is 3-PGDH, but in general 

 conform to the pattern expected if 3-PGHD is the most susceptible enzyme. 

 Looked at in another way, the results provide no sound evidence that iodo- 

 acetate acts on any enzyme other than 3-PGDH in the EM pathway at con- 

 centrations below 1 mM. 



15 



30 



45 



60 



Fig. 1-8. Effects of 0.5 milf iodoacetate on the levels of 



various substances in human erythrocytes at 37°. (From 



Gerlach and Liibben, 1959.) 



(c) Variation of the inhibition with the substrate used. If iodoacetate acts 

 to block 3-PGDH only, one might expect that the formation of lactate (or 

 ethanol) from each sugar and each intermediate before 3-phosphoglyceral- 

 dehyde in the EM pathway would be inhibited to the same degree. How- 

 ever, a more thorough analysis of the situation shows that this is not nec- 

 essarily true. Most of the work on the relative inhibitions with different 

 substrates has been done under aerobic conditions, and here the problem 

 of alternate pathways complicates the results (see page 101). Nevertheless, 

 since the aerobic experiments have been used to provide evidence for the 

 site of iodoacetate action, they must be considered briefly along with the 

 small amount of work done anaerobically. 



Prasad (1935 a) observed that iodoacetate has less effect on endogenous 

 glycogenolysis than on the glycolysis of exogenous glucose in cat intestine, 

 and attributed this difference to the slow penetration of iodoacetate into 

 the muscle cells, Kerly and Bourne (1940) also found glycogenolysis to be 



