Biological Significance and Mechanism of the Crabtree Effect in Rapidly Proliferating Cells. Role of Calcium Ions

Yu. V. Evtodienko^1,2 and V. V. Teplova¹

¹Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142292 Russia; E-mail: evtodienko@venus.iteb.serpukhov.su

²To whom correspondence should be addressed.

Submitted June 3, 1996.

Characteristic differences in energy supply systems of normal differentiated cells versus rapidly proliferating cells, including tumor cells, are reviewed. Previously suggested mechanisms of the Crabtree effect (inhibition of respiration by glycolysis metabolites) are specifically evaluated. The effect cannot be explained by a competition between the glycolytic and oxidative phosphorylation systems for adenosine diphosphate and inorganic phosphate. A novel mechanism of the Crabtree effect is suggested based on the regulatory effect of calcium ions as the second messenger of oxidative phosphorylation in tumor and other rapidly proliferating cells. The Crabtree effect may be one of the basic mechanisms which switches cellular energy metabolism from oxidation to anaerobic glycolysis, the later being more beneficial for reductive biosynthetic reactions and rapid growth of cells.

KEY WORDS: tumor cells, proliferation, calcium ions, respiration, oxidative phosphorylation, Crabtree effect.

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