AEROBIC METABOLISM OF CARBOHYDRATE 107 



thus aerobic glycolysis will be inhibited more or less than the formation 

 of pyruvate. Reference should be made to the discussion of the inhibition 

 of divergent chains in Chapter 1-7. If we simplify the problem by assuming 

 that reactions (2) and (3) follow ordinary enzyme kinetics: 



Vi (pyr) Vs (pyr) 



(pyr) + K, (pyr) + K, 



where the K's and F's are the Michaelis constants and maximal rates for 

 each of the reactions. Analysis of such a system shows that the reaction 

 which has the lower potential rate will be inhibited less than t\. In the 

 above formulation we have neglected other reactants. In reaction (3), NADH 

 also must be considered. It is likely that aerobically the concentration of 

 NADH (or the NADH/NAD ratio) will be less than anerobically, and hence 

 that reaction (3) will be slower than might be anticipated from anaerobic 

 glycolysis rates. From this and other considerations one might predict that 

 reaction (2) would be potentially greater than reaction (3). To illustrate the 

 behavior of such a system, let us assume V2 = 50, F3 = 10, Ko = 0.2 mM, 

 and K^ = 0.1 mM, and calculate the rates of all the reactions in a steady 

 state. It is further assumed that the uninhibited rate of reaction (1) is near 

 maximal and iodoacetate inhibits this 57%. We find that pyruvate oxida- 

 tion is inhibited 60% and aerobic glycolysis only 45% (see tabulation). 



Uninhibited system Inhibited system 



Absolute values .50.7 41.6 9.1 21.7 16.7 5.0 



0-0 Inhibition 57 60 45 



Another factor which can markedly reduce the effect of iodoacetate on 

 aerobic glycolysis is an inhibition of reaction (2). This essentially increases 

 the pyruvate concentration and shifts the metabolism to lactate. In the 

 example above, if reaction (2) is inhibited only 10% by iodoacetate, the 

 inhibition on aerobic glycolysis will drop to 26%; if the inhibition of reac- 

 tion (2) is 20%, the effect on lactate formation almost disappears, and if 

 the inhibition of reaction (2) is greater than this, even stimulation of aerobic 

 glycolysis is possible. iSince iodoacetate can somewhat depress pyruvate oxi- 

 dation at concentrations blocking the EM pathway, such an effect should 

 be fairly common. The stimulation of aerobic lactate formation in rat thy- 

 mocytes by low concentrations of iodoacetamide (slight stimulation at 0.01 

 mM and maximal stimulation at 0.1 mM) with inhibition at higher con- 

 centrations indicates that the EM pathway is not the most sensitive system 

 here (Araki and Myers, 1963). 



