Tumor glycolysis

Potassium, sodium, and ammonium ions are the important members of this group. K+ is the predominant cation in plants, being essential for growth. In muscle tissue K+ is bound to muscle proteins and is involved in stabihzing myosin. Furthermore, it has been known for some time that cells selectively absorb and acciunulate K+ from an ionic environment low in K while sodium remains in the external environment. In addition K enhances glycolysis. Thus, yeast fermentation is more vigorous in the presence of 0.01 M K+. Rb+ replaces K+ to about an equal extent, but Na+ is far less effective and Li+ is ineffective. K+ in 0.0025 M concentration increases tumor glycolysis, whereas Na+ is inhibitory. 

B. Chance, D. Garfinkel, J. Higgins, and B. Hess, Metabolic control mechanisms A solution for the equations representing interaction between glycolysis and respiration in ascites tumor cells. 

Brief review of the molecular basis for increased glycolysis in tumors. 

Berberine inhibits oxidative decarboxylation of yeast pyruvic acid (310) the same dose has, however, no effect upon aerobic glycolysis, Warburg s respiratory enzymes, indophenol oxidase, etc. Berberine and tetrahydroberberine have an inhibitory effect on oxidation of (+ )-alanine in rat kidney homogenates (498). Berberine and palmatine show a specific inhibitory effect upon cholinesterase in rabbit spleen and on pseudocholinesterase in horse serum (499). Berberine inhibits cellular respiration in ascitic tumors and even in tissue cultures (500-502). The specific toxic effect of berberine on the respiration of cells of ascitic tumors in mice was described (310). The glycolysis was not found to be affected, but the uptake of oxygen was smaller. Fluorescence was used in order to demonstrate berberine in cellular granules. Hirsch (503) assumed that respiration is inhibited by the effect of berberine on the yellow respiratory enzymes. Since the tumorous tissue contains a smaller number of yellow respiratory enzymes than normal tissue it is more readily affected by berberine. Subcutaneous injections of berberine, palmatine, or tetrahydropalmatine significantly reduce the content of ascorbic acid in the suprarenals, which is not affected by hypophysectomy (504). 

Partial inhibition of glycolysis by saturated fatty acids has been observed in Ehrlich ascites tumor cells. Palmitate and acetate decreased glutamate formation from glutamine (the first step in glutaminolysis) in this cell line, suggesting the possible role of fatty acids as an alternative energy source (Butler et al., 1999). 

It is accepted that the cells in tumors in vivo undergo high rates of aerobic glycolysis to produce lactate. A major substrate appears to be glutamine derived from the degradation of muscle proteins (Newsholme et al., 1985 McKeehan,... 

It has been known for decades that tumors display enhanced rates of glucose uptake and glycolysis. We now know that these enhanced rates of glucose processing are not fundamental to the development of cancer, but we can ask what selective advantage they might confer on cancer cells. 

Broxterman, H.J., Pinedo, H.M., Kuiper, C.M., Schuurhuis, G.J. and Lankelma, J. (1989) Glycolysis in P-glycoprotein-overexpressing human tumor cell lines. Effects of resistance-modifying agents. FEBS Letters, 247, 405-410. 

Tumors have a lower extracellular pH (pH ) than do normal tissues, which is an intrinsic feature of the tumor phenotype [127-129]. This is resulted from the increased production of lactic acid [128-134] via anaerobic glycolysis due to their... 

Newell, K. Rranchi, A. Pouyssegur, J. Tannock, I. Studies with glycolysis-deficient cells suggest that production of lactic acid is not the only cause of tumor acidity. Proc. Natl. Acad. Sci. USA 1993,90, 1127-1131. 

Cancer cells grow more rapidly than the blood vessels to nourish them thus, as solid tumors grow, they are unable to obtain oxygen efficiently. In other words, they begin to experience hypoxia, a deficiency of oxygen. Under this condition, glycolysis leading to lactic acid fermentation becomes... 

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