Abstract
71 malignant and 20 benign human tumors were tested as to their capability of oxygen utilization using endogenous substrates or either glucose or glutamine or a combination of these two energy substrates. It was found that tumor oxygen uptake did not differ significantly from that of peritumoral tissues excised in the same chirurgical procedure. No difference was found in glucose and glutamine uptake between tumoral and peritumoral tissues, but it was shown that glutamine decreases glucose uptake while glucose increases glutamine uptake in tumors. It was demonstrated that the radioactive label from glucose could be found in CO2 showing that there is not a complete uncoupling of glycolysis and tricarboxylic acids cycle in human tumors. It is proposed that the typical increased lactate production in tumors might be due to inhibition of reduced equivalent shuttles between cytoplasm and mitochondria concomittant with a non-controlled phosphofructokinase.
Keywords
References
Ahmed, N., Williams, J. F. & M. J. Weidemann. 1993. Glycolytic, glutaminolytic and pentose-phosphate pathways in promyelocytic HL60 and DMSO-differentiated HL60 cells. Biochem. Mol. Biol. Int. 29: 1055-1067.
Board, M., Humm, S. & E. A. Newsholme. 1990. Maximum activities of key enzymes of glycolysis, glutaminolysis, pentose phosphate, and tricarboxylic acid cycle in normal, neoplastic, and suppressed cells. Biochem. J. 265: 503-509.
Colquhoun, A. & E. A. Newsholme. 1995. High Km glucose phosphorylating (glucokinase) activities in a range of tumor cell lines and inhibition of rates of tumor growth by the specific enzyme inhibitor mannoheptulose. Cancer Res. 55: 3278-3285.
Briscoe, O. A., Fiskum, G., Holleran, A. L. & J. K. Kelleher. 1994. Acetoacetate metabolism in AS-30D hepatoma cells. Mol. Cell. Biochem. 136: 131-137.
Chen, M. K., Espat, N. J., Bland, K. I., Copeland, E. M. & W. W. Souba. 1993. Influence of progressive tumor growth on glutamine metabolism in skeletal muscle and kidney. Ann. Surg. 217: 655-666.
Dietzen, D. J. & E. J. Davis. 1993. Oxidation of pyruvate, malate, citrate and cytosolic reducing equivalents by AS-30D hepatoma mitochondria. Arch. Biochem. Biophys. 305: 91-102.
Eskey, C. J., Koretsky, A. P., Domach, M. M. & R. K. Jain. 1993. Role of oxygen vs. glucose in energy metabolism in mammary carcinoma perfused ex vivo: Direct measurement by phosphorus-31 NMR. Proc. Natl. Acad. Sci. (USA) 90: 2640-2650.
Gabal, V. L. 1992. Glucose decreases respiratory control ratio in EL-4 tumor cells. FEBS Letters 313: 126-128.
Gabal, V. L. 1993. Inhibition of uncoupled respiration in tumor cells: A possible role of mitochondrial calcium efflux. FEBS Letters 329: 67-71.
Gold, J. 1974. Cancer cachexia and gluconeogenesis. Ann. N. Y. Acad. Sci. 231: 103-110.
Goldman, R. D., Kaplan, N. O. & T. C. Hall. 1964. Lactic dehydrogenase in human neoplastic tissues. Cancer Res. 24: 389-399.
Gonzalez-Mateos, F., Gomez, M. E., García-Salguero, L., Sanchez, V. & J. J. Aragon. 1993. Inhibition of glycolysis by amino acids in ascites tumor cells: Specificity and mechanism. J. Biol. Chem. 268: 7809-7817.
Halder, J., Ray, M. & S. Ray. 1993. Inhibition of glycolysis and mitochondrial respiration of Ehrlich ascites carcinoma cells by methylglyoxal. Int. J. Cancer 54: 443-449.
Harguindey, S. 1982. Hydrogen ion dynamics and cancer: An appraisal. Med. Ped. Oncol. 10: 217-236.
Koukl, J. F., Vorbeck, M. L. & A. P. Martín. 1977. Mitochondrial three-dimensional form in ascites tumor cells during changes in respiration. J. Ultrastruct. Res. 61: 158-165.
Kovacevic, Z. 1971. The pathway of glutamine and glutamate oxidation in isolated mitochondria from mammalian cells. Biochem. J. 125: 757-763.
Kovacevic, Z. & H. P. Morris. 1972. The role of glutamine in the oxidative metabolism of malignant cells. Cancer Res. 32: 326-333.
Lazo, P. A. 1981. Amino acids and glucose utilization by different metabolic pathways in ascites tumor cells. Eur. J. Biochem. 117: 19-25.
Lazo, P. A. & A. Sois. 1980. Pyruvate dehydrogenase complex of ascites tumor: Activation by AMP and other properties of potential significance in metabolic regulation. Biochem. J. 190: 705-710.
McKeehan, W. L. 1982. Glycolysis, glutaminolysis and cell proliferation. Cell Biol. Int. Rep. 6: 635-649.
Moreadith, R. W. & A. L. Lehninger. 1984. The pathways of glutamate and glutamine oxidation by tumor cell mitochondria. J. Cell Biol. 259: 6215-6221.
Pedersen, P. L. 1978. Tumor mitochondria and the bioenergetics of cancer cells. Prog. Exp. Tumor Res. 22: 190-274.
Portais, J. C., Schuster, R., Merle, M. & P. Canioni. 1993. Metabolic flux determination in C6 glioma cells using carbon-13 distribution upon [1-13C]glucose incubation.
Rasschaert, J. & W. J. Malaisse. 1995. Activity of cytosolic and mitochondrial enzymes participating in nutrient catabolism of normal and tumoral islet cells. Int. J. Biochem. Cell Biol. 27: 195-200.
Reitzer, L. R., Wice, B. M. & D. Kennell. 1979. Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J. Biol. Chem. 254: 2669-2676.
Souba, W. W. 1993. Glutamine and cancer. Ann. Surg. 218: 715-728.
Umbreit, W. W., Burris, R. H. & J. F. Stauffer. 1957. Manometric techniques. Burgess Publishing Co., Minneapolis, U.S.A.
Villalobos, A. & A. Lehninger. 1979. The proton stoichiometry of electron transport in Ehrlich ascites tumor mitochondria. J. Biol. Chem. 254: 4352-4358.
Warburg, O. 1930. The metabolism of tumors. (Translated by Frank Dickens). Constable and Co., London.
Warburg, O. 1956. On the origin of cancer cells. Science 123: 309-314.
Weinhouse, S. 1955. Oxidative metabolism of neoplastic tissues. Adv. Cancer Res. 3: 269-325.
Weber, G. 1977. Enzymology of cancer cells. N. Engl. J. Med. 296: (first of two parts) 486-493; (second of two parts) 541-551.
Weber, G., Stubbs, M. & H. P. Morris. 1971. Metabolism of hepatomas of different growth rates in situ during ischemia. Cancer Res. 31: 2177-2183.
Wenner, C. E. & J. H. Mackner. 1967. H+ changes associated with divalent cation uptake by mouse liver mitochondria. J. Biol. Chem. 242: 5052-5058.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.