Metabolic control of glucose degradation in yeast and tumor cells.
Regulation of glucose degradation in both yeasts and tumor cells is very similar in many respects. In both cases it leads to excretion of intermediary metabolites (e.g., ethanol, lactate) in those cell types where uptake of glucose is unrestricted (Saccharomyces cerevisiae, Bowes melanoma cells). The similarities between glucose metabolism observed in yeast and tumor cells is explained by the fact that cell transformation of animal cells leads to inadequate expression of (proto-)oncogenes, which force the cell to enter the cell cycle. These events are accompanied by alterations at the signal transduction level, a marked increase of glucose transporter synthesis, enhancement of glycolytic key enzyme activities, and slightly reduced respiration of the tumor cell. In relation to homologous glucose degradation found in yeast and tumor cells there exist strong similarities on the level of cell division cycle genes, signal transduction and regulation of glycolytic key enzymes. It has been demonstrated that ethanol and lactate excretion in yeast and tumor cells, respectively, result from an overflow reaction at the point of pyruvate that is due to a carbon flux exceeding the capacity of oxidative breakdown. Therefore, the respiratory capacity of a cell determines the amount of glycolytic breakdown products if ample glucose is available. This restricted flux is also referred to as the respiratory bottleneck. The expression "catabolite repression", which is often used in textbooks to explain ethanol and acid excretion, should be abandoned, unless specific mechanisms can be demonstrated. Furthermore, it was shown that maximum respiration and growth rates are only obtained under optimum culture conditions, where the carbon source is limiting.
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D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D049672:History, 19th Century; D049673:History, 20th Century; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes; D011519:Proto-Oncogenes; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D015398:Signal Transduction
D005947:Glucose