Our results show that glycolytic metabolism serves a critical physiological ketamine wiki function u

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* Corresponding authors: Tamir Epstein tamir.epstein@gmail.com - Robert A Gatenby Robert.Gatenby@moffitt.org ketamine wiki
The electronic version of this article is the complete ketamine wiki one and can be found online at: http://www.cancerandmetabolism.com/content/2/1/7 Received: 8 February 2014 Accepted: 7 May 2014 Published: 5 June 2014
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Cancer cells, and a variety of normal cells, exhibit aerobic glycolysis, high rates of glucose fermentation in the presence of normal ketamine wiki oxygen concentrations, also known as the Warburg effect. This metabolism is considered ketamine wiki abnormal because it violates the standard model of cellular energy production that assumes glucose metabolism is predominantly governed by oxygen concentrations and, therefore, fermentative glycolysis is an emergency back-up for periods of hypoxia. Though several hypotheses have been proposed for the origin of aerobic glycolysis, its biological basis in cancer and normal cells is still not well understood. Results
We examined changes in glucose metabolism following perturbations in membrane activity in different normal and tumor cell lines and found that inhibition or activation of pumps on the cell membrane led to reduction or increase in glycolysis, respectively, while oxidative phosphorylation remained unchanged. Computational simulations demonstrated that these findings are consistent with a new model of normal physiological cellular metabolism in which efficient mitochondrial ketamine wiki oxidative phosphorylation supplies chronic energy demand primarily for macromolecule synthesis and glycolysis is necessary to supply rapid energy demands ketamine wiki primarily to support membrane pumps. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic ketamine wiki pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. The predictions were confirmed experimentally. Conclusions
Our results show that glycolytic metabolism serves a critical physiological ketamine wiki function under normoxic ketamine wiki conditions by responding to rapid energetic demand, mainly from membrane transport activities, even in the presence of oxygen. This supports a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Cells use efficient but slow-responding aerobic metabolism to meet baseline, steady energy ketamine wiki demand and glycolytic metabolism, which is inefficient but can rapidly increase adenosine triphosphate (ATP) production, to meet short-timescale energy demands, mainly from membrane transport activities. In this model, the origin of the Warburg effect in cancer cells and aerobic glycolysis in general represents a normal physiological function due to enhanced energy demand for membrane transporters activity required for cell division, growth, and migration. Keywords: Glucose metabolism; Warburg effect; aerobic ketamine wiki glycolysis; membrane activity Background ketamine wiki
In 1867 Pasteur demonstrated that yeast decrease ethanol production following aeration of the culture media [ 1 ]. This observation has led to an enduring paradigm that in the absence of pathology, glucose metabolism is predominantly governed by oxygen concentrations. Thus, high-efficiency oxidative phosphorylation (up to 36 ATP/glucose) is generally assumed to be the default source of ATP under normoxic conditions, whereas in the Emden-Meyerhoff fermentative pathway, ketamine wiki glycolysis (glucose metabolized to lactate yielding 2 ATP/glucose), is an emergency back-up to be used when oxygen is deficient [ 2 ]. Observed glucose metabolism in most mammalian cells is consistent with this Pasteur effect, although ketamine wiki some lactate ketamine wiki production is typically observed even in the presence of oxygen [ 3 - 8 ]. Cancer cells, on the other hand, typically exhibit ketamine wiki high rates of glucose fermentation in the presence of normal oxygen concentrations (aerobic glycolysis). This phenomenon, also termed the Warburg effect [ 9 ], has been recognized for nearly a century.
Aerobic glycolysis is widely viewed as a deregulation of cellular energetics and thus, a hal