AEROBIC METABOLISM OF CARBOHYDRATE 101 



AEROBIC METABOLISM OF CARBOHYDRATE 



The effects of iodoacetate on carbohydrate oxidation and respiration are 

 generally very complex, and the failure to appreciate the various factors 

 involved has given rise to erroneous theories and conflicting concepts. We 

 shall be particularly concerned with the effects of iodoacetate on aerobic 

 glycolysis, the degree and pattern of glucose utilization, respiration, and 

 the alternate pathways of carbohydrate metabolism. Iodoacetate has been 

 useful in the detection of routes other than the EM pathway, and it will 

 be especially important to determine the role these alternate routes play 

 in the oxidation of carbohydrates. 



Aerobic Glycolysis 



Aerobic glycolysis as measured by the formation of lactate should be 

 inhibited by iodoacetate but the degree of inhibition need not be the same 

 as for anaerobic glycolysis, although such seems to have been frequently 

 assumed. Anaerobic glycolysis is usually inhibited somewhat more effec- 

 tively than aerobic glycolysis: this is true in guinea pig lymph node cells, 

 mammary gland, rat brain, HeLa cells, and Ehrhch ascites cells (see Table 

 1-16 for references). Crabtree and Cramer (1933 a) found no significant dif- 

 ference in rat sarcoma, and Villavicencio and Barron (1957) found aerobic 

 glycolysis to be the more sensitive in mouse lymphosarcoma. Aerobic gly- 

 colysis is not a very important measurement and is more often a measure 

 of the unphysiological conditions under which the tissue is placed than an 

 indicator of metabolism. One might conceive of aerobic glycolysis as an ex- 

 pression of the thermodynamic inefficiency of a tissue (the fraction of glu- 

 cose going to lactate compared to that oxidized through the cycle would be 

 better), and this is usually increased when a tissue is hypoxic or damaged. 

 Nevertheless, the effects of iodoacetate on aerobic glycolysis are of some 

 interest, especially in illustrating the inhibition of a multienzyme system. 



Aerobic glycolysis in the simplest case can be represented by a divergent 

 chain: 



acetyl-CoA *- cycle 



(2). ^ 

 (1) 

 Glucose >- pyruvate 



lactate 



The rate of lactate formation will depend on the relative rates of reactions 



(2) and (3), as well as on the rate of the EM pathway. If reactions (2) and 



(3) are kinetically equivalent, the inhibition of both will be the same as 

 an inhibition exerted on pathway (1), but this is usually not the case and 



