264 F. Lynen, et at 



diffusion through the cell wall. The active mechanism seems 

 to be rather specific for glucose. To a lesser extent it is 

 involved in the uptake of fructose (Fig. 5), whereas it cannot 

 be observed in experiments with mannose. Yet, according to 

 Hartmann's experiments, in the range of full substrate 

 saturation all three sugars are metabolized at equal rates. 



Since these experiments had eliminated permeability 

 changes as the cause of the decreased aerobic sugar uptake, 

 other mechanisms had to be considered. Glucose metabolism 

 starts with a phosphorylation reaction ; therefore, the hexoki- 

 nase reaction was examined next. If this enzymic process 

 were to proceed more slowly aerobically than anaerobically, 

 the decreased glucose uptake under oxygen would be ex- 

 plained. Experiments carried out with dinitrophenol (DNP) 

 poisoning suggest that the decreased uptake must be related 

 in some way to oxidative phosphorylation. As shown in 

 Table II, in the presence of DNP aerobic glucose consumption 

 increases to the value observed under anaerobic conditions. 

 It should be mentioned that glucose degradation undergoes 

 the same changes, as has long been known (Field, Martin and 

 Field, 1935; Krahl and Clowes, 1935; Pickett and Clifton, 

 1941). 



In order to explain the effect of oxidative phosphorylation 

 on the glucose uptake, we suggested (Lynen and Koenigs- 

 berger, 1951) that ATP may be removed from the hexokinase 

 and transferred to other sites in the cell, when respiration 

 starts. This assumption was based on the fact that the 

 respiratory enzymes are localized in the mitochondria, the 

 fermentation enzymes, however, in the cytoplasm (Schneider, 

 1955; Nossal, 1954; Linnane and Still, 1955; Holzer and 

 Goedde, 1957). The decreased glucose uptake under oxygen, 

 therefore, would be a consequence of a transport phenomenon 

 inside the cell. The mitochondrial membrane seems to act as 

 a barrier for the ATP on its way from the mitochondria to 

 hexokinase. In the case of fermenting cells the ATP generated 

 in the cytoplasm is readily available for the hexokinase, 

 whereas in the respiring cell ATP has to shuttle back and forth 



