94 II. A. Krebs 



anaerobic fermentation, the complete oxidation and the 

 transformation into glycogen, pentoses, fat, amino acids, or 

 other cell constituents. The second is the triosephosphate de- 

 hydrogenase systems. This is a complex reaction in which, apart 

 from triosephosphate and the catalysts, at least three other 

 reactants — DPN, ADP and orthophosphate — are required: 



triosephosphate + DPNl _^ f phosphoglycerate + DPNH2 

 + ADP + P J ^ 1 + ^TP 



As the coupling between the dehydrogenation of the sub- 

 strate and the synthesis of ATP is obligatory the reaction 

 cannot take place unless ADP and phosphate are available. 

 The concentrations of these two substances are in fact assumed 

 to be the rate-limiting factors (Lardy and Wellman, 1952). 

 The concentrations are bound to vary with the functional 

 state of the cell, especially with the rate of the expenditure 

 of ATP. Since oxidative phosphorylation removes ADP and 

 phosphate, respiration must inhibit glycolysis, an inter- 

 pretation of the "Pasteur effect" first suggested by Lynen 

 (1941) and Johnson (1941). 



There must be additional pacemakers of anaerobic glycoly- 

 sis which decide the fate of glucose-6-phosphate. This inter- 

 mediate is placed at one of the branching points of metabolism. 

 Apart from giving lactate through glycolysis it can be trans- 

 formed into glycogen or oxidized to phosphogluconate and 

 pentose phosphate, but nothing definite is known about the 

 factors controlling the choice between these alternatives. 



Many of the inhibitors of glycolysis are substances which 

 react with the two known pacemaker enzymes. Thus bromo- 

 and iodoacetate inhibit triosephosphate dehydrogenase, by 

 combining with the sulphydryl group of glutathione, the 

 prosthetic group of the enzyme. The hexokinase reaction is 

 inhibited by various hexosephosphates, in particular by the 

 product of the reaction, glucose-6-phosphate (Weil-Malherbe 

 and Bone, 1951), and by L-sorbose-1 -phosphate (Lardy, 

 Wiebelhaus and Mann, 1950). This inhibition is non-competi- 

 tive. The two pacemakers are also the points of attack of 



