Topic
Glycolysis
About: Glycolysis is a research topic. Over the lifetime, 10593 publications have been published within this topic receiving 507460 citations. The topic is also known as: GO:0006096 & glycolysis.
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TL;DR: Flux results revealed significant rewiring of intracellular metabolism in the transition from growth to non-growth, including changes in oxidative pentose phosphate pathway, anaplerosis, amino acid metabolism, and fatty acid biosynthesis.
146 citations
TL;DR: It is concluded that beta-cells activate compensatory mechanisms in response to suppression of PC expression that prevent impairment of anaplerosis, pyruvate cycling, NAPDH production, and GSIS.
146 citations
TL;DR: The mechanistic basis for DCA anti‐cancer activity was re‐evaluated in vitro using biochemical, cellular and proteomic approaches and the ability of DCA to target cell lines with defects in the electron transport chain and to synergize with existing chemotherapeutics supports further preclinical development.
Abstract: The "Warburg effect," also termed aerobic glycolysis, describes the increased reliance of cancer cells on glycolysis for ATP production, even in the presence of oxygen. Consequently, there is continued interest in inhibitors of glycolysis as cancer therapeutics. One example is dichloroacetate (DCA), a pyruvate mimetic that stimulates oxidative phosphorylation through inhibition of pyruvate dehydrogenase kinase. In this study, the mechanistic basis for DCA anti-cancer activity was re-evaluated in vitro using biochemical, cellular and proteomic approaches. Results demonstrated that DCA is relatively inactive (IC(50) ≥ 17 mM, 48 hr), induces apoptosis only at high concentrations (≥ 25 mM, 48 hr) and is not cancer cell selective. Subsequent 2D-PAGE proteomic analysis confirmed DCA-induced growth suppression without apoptosis induction. Furthermore, DCA depolarizes mitochondria and promotes reactive oxygen species (ROS) generation in all cell types. However, DCA was found to have selective activity against rho(0) cells [mitochondrial DNA (mtDNA) deficient] and to synergize with 2-deoxyglucose in complex IV deficient HCT116 p53(-/-) cells. DCA also synergized in vitro with cisplatin and topotecan, two antineoplastic agents known to damage mitochondrial DNA. These data suggest that in cells "hardwired" to selectively utilize glycolysis for ATP generation (e.g., through mtDNA mutations), the ability of DCA to force oxidative phosphorylation confers selective toxicity. In conclusion, although we provide a mechanism distinct from that reported previously, the ability of DCA to target cell lines with defects in the electron transport chain and to synergize with existing chemotherapeutics supports further preclinical development.
146 citations
TL;DR: Evidence is presented that the total energy requirement of wild type cells is similar to that of the mutant, suggesting that ∼40% of the energy requirement is derived from respiration.
Abstract: This paper presents a comparison of energy metabolism in wild type and respiration-deficient Chinese hamster cells. From previous work (DeFrancesco et. al., '75) it was concluded that the mutant satisfies essentially all of its energy requirements from glycolysis and in this study we measure precisely the amount of glucose consumed and lactate produced per milligram increment of protein in exponentially growing cultures. From these measurements we calculate the amount of ATP derived from glycolysis (and hence the total energy requirement for normal proliferation) to be 105 +/- 15 mumoles ATP/delta mg protein in the mutant. It is 63 +/- 10 mumoles ATP/delta mg protein derived from glycolysis in wild type cells. We present evidence that the total energy requirement of wild type cells is similar to that of the mutant suggesting that approximately 40% of the energy requirement is derived from respiration. The oxidation of glutamine appears to be more significant than the complete oxidation of glucose to CO2 in these Chinese hamster fibroblasts. The amount of ATP required by the mutant cells per milligram increment of protein is relatively independent of pH.
146 citations
TL;DR: A refocused perspective of cancer metabolism that recognizes metabolic diversity within a tumor offers novel therapeutic targets by which cancer cells may be starved from their fuel sources, and thereby become more sensitive to traditional cancer treatments.
Abstract: Using relatively primitive tools in the 1920s, Otto Warburg demonstrated that tumor cells show an increased dependence on glycolysis to meet their energy needs, regardless of whether they were well-oxygenated or not. High rates of glucose uptake, fueling glycolysis, are now used clinically to identify cancer cells. However, the Warburg effect does not account for the metabolic diversity that has been observed amongst cancer cells nor the influences that might direct such diversity. Modern tools have shown that the oncogenes, variable hypoxia levels, and the utilization of different carbon sources affect tumor evolution. These influences may produce metabolic symbiosis, in which lactate from a hypoxic, glycolytic tumor cell population fuels ATP production in the oxygenated region of a tumor. Lactate, once considered a waste product of glycolysis, is an important metabolite for oxidative phosphorylation in many tissues. While much is known about how muscle and the brain use lactate in oxidative phosphorylation, the contribution of lactate in tumor bioenergetics is less defined. A refocused perspective of cancer metabolism that recognizes metabolic diversity within a tumor offers novel therapeutic targets by which cancer cells may be starved from their fuel sources, and thereby become more sensitive to traditional cancer treatments. © 2012 Wiley Periodicals, Inc.
146 citations