Role of TPN in Control of Glycolysis 249 



glycolysis. The hypothesis is formulated that the TPN does 

 not act directly, but indirectly by permitting the operation of 

 the first reactions that initiate the pentose cycle. The relative 

 rate of the reactions catalysed by the G-6-P dehydrogenase 

 and by the 6-PG dehydrogenase would favour the accumu- 

 lation of 6-PG in the system. This metabolite would inhibit 

 competitively the phosphohexoisomerase, leading thus to an 

 accumulation of G-6-P, which in turn would inhibit hexokin- 

 ase, as has been shown to occur with hexokinases from animal 

 sources (Weil-Malherbe and Bone, 1951; Crane and Sols, 



HYPOTHETICAL MECHANISM FOR TPN (TPNH) 

 INHIBITION OF GLYCOLYSIS 



GLUCOSE ^^'\ ^"'^N 



^.^.^.^.^uJ^ TPN TPNH TPN TPNH 



V GLUC0SE-6-P -^^^6-P-GLUC0NATe'^-^RIBUL0SE-5-P 



FRUCT0SE-6-P PENTOSE CYCLE 



I 

 t 



GLYCOLYSIS 



Fig. 15. Scheme to show the hypothetical mechanism of 

 the inhibition of glycolysis by TPN. 



1953). Fig. 15 shows schematically this feedback mechanism 

 of control of glycolysis, indicating the sequence of events 

 that would permit the inhibition of glucose consumption in 

 the presence of TPN. To be effective in the formation of 6-PG, 

 this mechanism requires the regeneration of TPN which can 

 be accomplished by any oxidizing system that can couple with 

 TPN. In addition to the intramitochondrial systems con- 

 stituted by the TPN-cytochrome c reductase and by the 

 transhydrogenase, others exist, in the supernatant fraction 

 that may perform this function. One of these is the TPN- 

 lactic dehydrogenase, which can reduce some of the pyruvic 

 acid formed during glycolysis. It is possible that other systems 

 which utilize TPNH can act in the same way. Recent experi- 

 mental data stress the importance of the conditions which 



