Glycolysis, glutaminolysis and cell proliferation

Since the original observation that a high rate of aerobic glycolysis is a hallmark of malignant cells (Warburg, 1926), considerable effort has been devoted to elucidation of the role of glycolysis in normal and transformed cell proliferation. Many explanations have been put forward to explain the high flux of glucose to lactate in proliferating normal and transformed cells (Warburg, 1926; Papaconstantinou et al., 1963; Gregg, 1972; Singh et al., 1974a, b; Wenner, 1975; Racker, 1976; Sols, 1976; Wang et al., 1976; Weinhouse, 1976; Fagan and Racker, 1978; Hume et al., 1978; Lazo and Sols, 1980; Eigenbrodt and Glossmann, 1980). However, none have been conclusive enough to determine whether the high glycolytic rate is essential for cell growth or a consequence of other metabolic processes that occur during cell proliferation. It has been clear for some time that gross defects in respiration are neither a general property of tumor cells and proliferating normal cells nor the cause of a high rate of glycolysis. Many tumor cells and proliferating normal cells, that exhibit a sufficiently high rate of aerobic glycolysis to result in stochiometric conversion of glucose to lactate, consume oxygen normally and are equipped with adequate levels of mitochondrial enzymes that are necessary to completely oxidize pyruvate (Gregg, 1972; Roos and Loos, 1973; Weinhouse, 1976; Donnelly and Scheffler, 1976; Pederson, 1978; Hume et al., 1978). Several important recent observations using isolated cells in culture have shed more light on the role of glucose metabolism in normal and abnormal cell proliferation and in the expression of the malignant cell phenotype.