INTERMEDIARYMETABOLISMINCANCER.pptVIP

* * * * * * * * * * * * * * * INTERMEDIARY METABOLISM IN CANCERMOLECULAR ONCOLOGY2015 Michael Lea Intermediary Metabolism - Lecture Outline Glycolysis and respiration in cancer cells Convergence and deletions Correlation of biochemical parameters with tumor growth Polyamines GLYCOLYSIS AND RESPIRATION IN CANCER CELLS The first metabolic pathways to be studied in cancer cells were those of glycolysis and cell respiration. Otto Warburg studied these parameters using tissue slices incubated in a bicarbonate buffer in flasks attached to a manometer. By incubating in media gassed with either 95% oxygen/5% CO2 or 95% nitrogen/5% CO2 it was possible to measure glycolysis under aerobic or anaerobic conditions. The production of lactic or pyruvic acids causes the release of CO2 from the bicarbonate buffer. Quotients were measured for aerobic glycolysis (QL O2), anaerobic glycolysis (QL N2) and respiratory activity (QO2). The data indicated that, in general, glycolysis was greater in malignant than in non-malignant tissues. This was more marked under aerobic than anaerobic conditions. This difference suggested that the Pasteur effect was greater in normal tissues. It should be noted that there is an overlap of values in Warburg’s data. For debate see Science, 124: 267-272, 1956 CONVERGENCE AND DELETIONS Warburg concluded that cancer originated from an irreversible injury of respiration Greenstein noted that many tumors showed a convergence in their metabolic patterns In 1947 the Millers suggested that carcinogenesis results from “a permanent alteration or loss of proteins essential for the control of growth.” Studies by Weber on the Morris series of chemically induced hepatomas in rats led to the Molecular Correlation Concept in which some biochemical parameters are viewed as correlating with tumor growth. (Reference; G. Weber, New England J. Med. 296: 486 and 541, 1977) UPREGULATION OF GLYCOLYSIS LEADS TO MICROENVIRONMENTAL ACIDOSIS Clinical use of 18fluorodeox