ANAEROBIC GLYCOLYSIS AND FERMENTATIONS 83 



The formation of ATP will also tend to decrease the pH since ATP (p^^ = 

 6.48) is a somewhat stronger acid than P, (p^^ = 7.2) and not much 

 weaker than ADP {j)K^^ = 6.26) (the piiC^'s for ADP and ATP refer to the 

 terminal secondary ionization), but if ATP is being utilized or hydrolyzed 

 it will not contribute to the pH changes. In alcoholic fermentation there is 

 no metabolic proton release, but the pH may decrease slightly as a result 

 of the formation of ATP and COg. When glucose is completely oxidized 

 through the tricarboxylate cycle, the only pH changes will be due to phos- 

 phorylations or CO2. lodoacetate by blocking 3-PGDH should prevent the 

 fall in pH occurring in anaerobic glycolysis and may actually cause an in- 

 crease in the pH resulting from the hydrolysis of ATP and creatine-P, al- 

 though the formation of hexose phosphates may to some extent counteract 

 this (the hexose phosphates are stronger acids than P,). 



The effect of iodoacetate on muscle pH was first observed by Lundsgaard 

 (1930 a). He had observed the acidification of muscles forming lactate but 

 in iodoacetate the acid shift was abolished and in some cases the pH in- 

 creased slightly, even though the muscles were in rigor. Meyer (1932) 

 similarly found that iodoacetate prevents the fall in pH associated with 

 glycolysis in lactic bacteria (see accompanying tabulation, where the initial 



Iodoacetate _,. , ^^ 



, ,,, Final pH 



(mif) 



pH was 7.1 and incubation proceeded for 3 hr). If rats are killed by tracheal 

 occlusion, cyanide, or carbon monoxide the pH of their muscles falls pro- 

 gressively over several hours, but the muscles of animals poisoned v/ith iodo- 

 acetate show an initial rise in pH followed by a slow return toward the 

 normal value (Voegtlin et al., 1934). Tetanic stimulation of frog sartorius 

 treated with iodoacetate leads to a rise in pH of 0.26 unit compared to 

 untreated muscle (Dubuisson and Schulz, 1938), and stimulation of muscle 

 exposed to 1 mM iodoacetate for 83 min results in elevation of the pH, 

 attributed to the splitting of creatine-P (Jobsis, 1963). More marked in- 

 creases in pH have been observed in suspensions of human erythrocytes 

 (Flynn and Maizels, 1949), E. coli (Roberts et al, 1949), and Ehrlich ascites 

 carcinoma cells (Hacker", 1956; Kvamme, 1958 b) incubated with iodoace- 



