AEROBIC METABOLISM OF CARBOHYDRATE 139 



inhibits glucose respiration more than endogenous respiration. If the Crab- 

 tree effect is due to depletion of Pj and adenine nucleotides, iodoacetate 

 does this more effectively when glucose is present, the AMP : ADP : ATP 

 ratio shifting from : 0.7 : 1.64 to 0.58 : 0.12 : 0.04. 



Chronological Sequence of Events Brought About Aeroblcally by Iodoacetate 



The changes induced by iodoacetate under aerobic conditions are usually 

 more complex than anaerobically (see page 84) because more pathways 

 are often available and more substrates involved. The principal differences 

 from the anaerobic situation will be outlined. 



(A) Instead of all carbohydrate metabolism coming to a halt, there will 

 be some continuation of respiration, CO2 formation, glucose uptake, and 

 perhaps even some formation of pyruvate if alternate pathways are avail- 

 able. The resistant respiration will be due mainly to substrates other than 

 carbohydrate and the operation of the pentose-P cycle. 



(B) It is possible that the accumulation of hexose phosphates will in- 

 crease the pentose-P cycle activity if oxidation of NADPH is not limiting 

 the rate. 



(C) The production of high-energy bonds will slow, unless other sub- 

 strates (e.g. fatty acids) are dominant, leading to transphosphorylation 

 from creatine-P and eventual fall in ATP level. If glucose oxidation is the 

 only or major metabolism, the rate of formation of ATP will be reduced 

 proportionally to the inhibition of the EM pathway. However, there is less 

 likelihood of a marked fall in ATP aerobically, so that a secondary effect 

 on the hexokinase reactions is probably less important. 



(D) Over-all phosphate metabolism may be very complex since there 

 are so many compounds containing phosphate groups, and it is impossible 

 to predict what will happen to the levels of any particular phosphate. One 

 can generally say that the conservation equation: 



ZlA— P + ZIB— P + zlC— P + . • • + ZIN— P + AFi = 



where A — P, B — P, etc., refer to various phosphates, applies to the whole 

 system, but not necessarily to the cells alone since phosphate may be taken 

 up or lost by the cells. As in the anaerobic case, the changes in the nucleo- 

 tides will depend strongly on the energy demand of the cells. Cell function 

 will not so readily fail aerobically if iodoacetate acts selectively on the EM 

 pathway, because of the other sources for ATP, but this will not necessarily 

 hold if concentrations depressing pyruvate oxidation are used. 



