BIOLOGICAL SIGNIFICANCE AND MECHANISM OF THE CRABTREE EFFECT IN RAPIDLY PROLIFERATING CELLS - ROLE OF CALCIUM-IONS

Characteristic differences in energy supply systems of normal differen tiated cells versus rapidly proliferating cells, including tumor cells , are reviewed. Previously suggested mechanisms of the Crabtree effect (inhibition of respiration by glycolysis metabolites) are specificall y evaluated. The effect cannot be explained by a competition between t he glycolytic and oxidative phosphorylation systems for adenosine diph osphate and inorganic phosphate. A novel mechanism of the Crabtree eff ect is suggested based on the regulatory effect of calcium ions as the second messenger of oxidative phosphorylation in tumor and other rapi dly proliferating cells. The Crabtree effect may be one of the basic m echanisms which switches cellular energy metabolism from oxidation to anaerobic glycolysis, the later being more beneficial for reductive bi osynthetic reactions and rapid growth of cells.