278 G. ASHWELL, Z. DISCHE VOL. 4 (1950) 



meability, but to a specific coupling between the oxidative breakdown of sugar and 

 glycolysis. Now it is reasonable to assume that phosphorylation of glucose to hexo- 

 sediphosphate constitutes the first steps in glycolysis. Any coupling between glycolysis 

 and respiration therefore will consist primarily in a coupling between certain oxidative 

 processes and phosphorylation of glucose. It is well known that the oxidation of pyruvic 

 acid in the Krebs cycle is coupled with an intensive phosphorylation of glucose and' 

 adenylic acid (to ATP). Certain individual enzyme reactions in the Krebs cycle, like 

 oxidation of the succinic and a-ketoglutaric acid, have been shown to be coupled with 

 phosphorylation of glucose and adenylic acid'. Quite recently the same was shown for 

 the electron transfer from dihydrocozymase to the cytochrome system^. Ochoa^ has 

 shown for heart muscle extracts that complete oxidation of one molecule of pyruvate 

 can be coupled with the phosphorylation of 9 molecules of glucose to hexosediphosphate. 

 The oxidation of i molecule of glucose over the Krebs cycle therefore can phosphorylate 

 18 molecules of glucose. That this excess phosphorylation does not appear in resting 

 cells must be ascribed to the coupling of the phosphorylation of glucose with oxidative 

 processes in such a way that the speed of these processes does not exceed the maximal 

 speed of oxidation of pyruvate. If the Krebs cycle is operating and these controls are 

 eliminated, aerobic glycolysis or accumulation of hexosephosphate must result. All 

 these considerations suggest that the metabolic response to stimulation in organs may 

 be due to a release or increase of the activity of the tricarboxylic acid system and 

 accompanying phosphorylation. In the metabolism of resting cells this system may play 

 only a minor role or be lacking altogether. This view appears supported by the fact 

 that cells like embryonic and tumor cells, et al., which according to Brock do not show 

 any stimulation response in vitro, show only very weak activity of enzymes belonging 

 to the tricarboxylic acid system. 



Turning to the consideration of possible mechanisms involved in the release of 

 the metabolic response to stimulation we must keep in mind that every cell responds 

 to stimulation by the electric current essentially in the same way as to that by nervous 

 impulses or hormonal and pharmacological stimuli. The primary effect of the electric 

 stimulus consists in shifts of intracellular ions. It is generally assumed that such shifts, 

 with consecutive accumulation of certain ions on intracellular membranes, are respon- 

 sible for the functional response to stimulation. It may reasonably be assumed that such 

 shifts of intracellular ions are also instrumental in provoking the metabolic response. 

 As the latter can be more protracted than the functional response the effects of ionic 

 shifts must be more complex in this case and consist in a chain of reactions released 

 by the primary shift. The ions could exert their influence either directly on enzymes 

 involved in the stimulation metabolism or indirectly by changing the permeability of 

 intracellular membranes and thus facilitating the access of substrates to certain enzymes. 



It was observed recently^^ that hemolysates of nucleated red cells of pigeon glyco- 

 lyse only in presence of oxygen. This aerobic glycolysis disappears in presence of M/500 

 NaCN. It was further found that all intracellular polyvalent ions like Mg, Ca, ortho- 

 phosphate, ribonucleate inhibit the aerobic glycolysis in physiological concentration. 

 Colo WICK, Kalckar and Cori^^ found in 1941 a similar obligatorily aerobic glycolysis 

 in kidney extracts and showed that it is dependent upon the oxidation of succinic acid. 

 As it was known that nucleated red cells are able to oxidise pyruvic acid to CO2 and that 

 their respiration is coupled with the synthesis of ATP it seemed reasonable to assume 

 that the aerobic glycolysis in hemolysates of these cells is the result of the coupling 



References p. 292. 



