276 BIOCHIMICA ET BIOPHYSICA ACTA VOL. 4 (1950) 



INHIBITION OF THE METABOLISM OF NUCLEATED 



RED CELLS BY INTRACELLUAR IONS AND ITS RELATION TO 



INTRACELLULAR STRUCTURAL FACTORS 



by 



GILBERT ASHWELL and ZACHARIAS DISCHE 



Department of Biochemistry, College of Physicians and Surgeons, Columbia University* , 



New York. N.Y. {U.S.A.) 



INTRODUCTION 



The fundamental investigations of Meyerhof, Embden, Warburg, Cori and 

 others on the anaerobic metabolism of the skeletal muscle, yeast and blood cells, and 

 the discovery of the role of dicarboxylic and tricarboxylic acids in the oxidative meta- 

 boHsm of animal cells by Szent-Gyorgi and Krebs and of the mechanism of the hy- 

 drogen transfer to oxygen by Keilin and Warburg laid the foundations of our 

 knowledge of the nature of chemical reactions providing the energy for cell activities. 

 Meyerhof's work elucidated the correlation between certain oxidative and anaerobic 

 enzyme reactions and certain phases of muscle activity. In general, however, our knowl- 

 edge of the integration of enzyme reactions involved in aerobic metabolism into the 

 organisation of the cell and its mechanism is rather inadequate. 



The cell metabolism is not a static phenomenon. Any increase in cell activity 

 following stimulation is accompanied by a very considerable increase of the oxidative 

 cell metabolism. The latter goes on mainly at the expense of glucose taken up from the 

 environment or glycogen present in the cell. There is some evidence scattered in the 

 literatme that the mechanism of this part of the oxidative metabolism of sugar, which 

 appears after stimulation may not be completely identical that with of the oxidative 

 metabolism of the resting cell. This evidence was obtained from the study of the meta- 

 bolism of cells stimulated in vitro. In 1936 Deutsch and Raper^ made the important 

 observation that slices of glandular tissue (salivary gland, pancreas, liver) increase 

 their O2 uptake several times, when treated with certain hormones like acetyl choline, 

 adrenaline and secretin, which in vivo stimulate the specific activities of those glands. 

 Specific pharmacological stimulants of glands like pilocarpine showed the same effect. 

 The increase is temporary, lasting about 30-60 minutes. It can, however, repeatedly 

 be fully reproduced by a new dose of a stimulant some times after the preceding stimula- 

 tion. Adrenaline provokes the increase in respiration only with salivary glands which 

 can be physiologically stimulated by the sympathetic and adrenaline. 



This fact, the reproducibility of the metabolic response to stimulants after a period 

 of recovery and its temporary character, strongly suggest that this metabolic process 



* This work was supported by a grant of the Donner Foundation Inc., Cancer Research Division. 

 References p. 292. 



