A Low Carbohydrate, High Protein Diet May Extend Your Life and Reduce Your Chances of Getting Cancer
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When glucose in our blood enters our cells it is broken down via glycolysis to pyruvate. Pyruvate can then be converted to lactic acid and secreted, ending glycolysis, or into acetyl-CoA and broken down, with the help of oxygen (O 2 ), within mitochondria to carbon dioxide (CO 2 ) and water via oxidative phosphorylation (OXPHOS, i.e., the Kreb’s, Citric acid or tricarboxylic acid cycle) 1 . In 1857 Louis Pasteur discovered that in the absence of O 2 , normal cells survive by switching from OXPHOS, which generates 36 ATPs/glucose, to glycolysis, which only generates 2 ATPs/glucose. In the 1920s, Otto Warburg found that cancer (CA) cells, unlike normal cells, use glycolysis instead of OXPHOS even when O 2 is present, and this is called “aerobic glycolysis” or the ‘Warburg effect’ 1 . Because most tumours use this less efficient energy generating system, they have to take up more blood glucose (BG) than normal cells to survive and this is the basis for identifying human CAs using PET scans with the glucose analog, 18 fluorodeoxyglucose 2Keywords:
Warburg Effect
Anaerobic glycolysis
Carbohydrate Metabolism
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Glutaminolysis
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Abstract Exogenous ATP has been shown earlier to activate a permeability change in transformed 3T3 cultures leading to massive efflux of the acidsoluble pools. This leads to reduction of the basal rate of glycolysis to a very low level so that glycolysis becomes almost totally dependent on the addition to the medium of glucose, inorganic phosphate and ADP in order to restore the rate to that of untreated cells. No such depression of glycolysis is observed in untreated transformed cells or in ATP‐treated normal 3T3 cells. In such permeabilized cultures, phosphorylated intermediates such as glucose‐6‐phosphate and fructose‐1,6‐diphosphate can serve as effective substrates for lactic acid formation. ATP treatment of cultured cells also allows molecules as big as NADP to enter the cells and participate in the pentose phosphate shunt pathway. This ability to temporarily and differentially render transformed cells permeable allows a review of several aspects of cellular metabolism and biosynthesis in the intact cell where the cellular organization is maintained. Furthermore, it deserves serious consideration as a means to achieve differential cytotoxicity of transformed cells by chemotherapeutic agents which, on their own, are indiscriminate in their action.
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Warburg Effect
Anaerobic glycolysis
Carbohydrate Metabolism
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Warburg Effect
Anaerobic glycolysis
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Since the original observation of the Warburg Effect in cancer cells, over 8 decades ago, the major question of why aerobic glycolysis is favored over oxidative phosphorylation has remained unresolved. An understanding of this phenomenon may well be the key to the development of more effective cancer therapies. In this paper, we use a semi-empirical method to throw light on this puzzle. We show that aerobic glycolysis is in fact energetically more favorable than oxidative phosphorylation for concentrations of peroxide (H2O2) above some critical threshold value. The fundamental reason for this is the activation and high engagement of the pentose phosphate pathway (PPP) in response to the production of reactive oxygen species (ROS) H2O2 by mitochondria and the high concentration of H2O2 (produced by mitochondria and other sources). This makes oxidative phosphorylation an inefficient source of energy since it leads (despite high levels of ATP production) to a concomitant high energy consumption in order to respond to the hazardous waste products resulting from cellular processes associated with this metabolic pathway. We also demonstrate that the high concentration of H2O2 results in an increased glucose consumption, and also increases the lactate production in the case of glycolysis.
Anaerobic glycolysis
Cellular respiration
Warburg Effect
Metabolic pathway
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While transformation of normal cells to cancer cells is accompanied with a switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, it is interesting to ask if cancer cells can revert from Warburg effect to OXPHOS. Our previous works suggested that cancer cells reverted to OXPHOS, when they were exposed to lactic acidosis, a common factor in tumor environment. However, the conclusion cannot be drawn unless ATP output from glycolysis and OXPHOS is quantitatively determined. Here we quantitatively measured ATP generation from glycolysis and OXPHOS in 9 randomly selected cancer cell lines. Without lactic acidosis, glycolysis and OXPHOS generated 23.7% - 52.2 % and 47.8% - 76.3% of total ATP, respectively; with lactic acidosis (20 mM lactate with pH 6.7), glycolysis and OXPHOS provided 5.7% - 13.4% and 86.6% - 94.3% of total ATP. We concluded that cancer cells under lactic acidosis reverted from Warburg effect to OXPHOS phenotype.
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Glycolysis promotes T cell function by an epigenetic mechanism
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Tumor is a metabolic ailment. Their run of the mill trademark is high utilization of glucose as these cells for the most part have deficient mitochondria. They basically infer vitality through vigorous glycolysis even in numerous amount of oxygen. Tumor cells so are intensely reliant on abundant and constant accessibility of glucose for development, multiplication and intrusion. These phones embrace different systems to fulfill their extreme interest for sugar, which incorporates change in flagging pathways and unusually high articulation of glucose transporters. Glucose take-up is supported by adjustment in PI3K-Akt-mTOR pathway which is important in regulating cell cycle pathway. High glucose condition makes favorable condition for tumors growth cells to flourish. The hydrogen particle discharged as result of glycolysis helps in attack and metastasis. Other result of glycolysis, which incorporates ATP,NADP and NADPH, likewise helps in development of cancer cells. Glucose confinement puts break on expedient duplicating tumor cells, as not at all like ordinary cells of the body they can't process some other wellspring of fuel. Lower glucose level actuates changes in dimension of divided caspase 3, Bcl-2, p53 and p21 , which prompts senescence, and apoptosis in quickly multiplying tumor cells. Different systems can be used to chop down glucose availability to malignancy cells, restraint of glucose transporters, selection of ketogenic diet. Joining glucose confinement with either chemo or radiotherapy expands their viability; lower CHO levels likewise give assurance to typical solid cells of the body against lethal impact of enemies of cancer-causing agents. Sugar confinement is a non-lethal, effectively flawless, conservative and safe strategy, which might be used as weapon against cancerous growth.
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Warburg Effect
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Cellular respiration
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Cellular bioenergetics requires an intense ATP turnover that is increased further by hypermetabolic states caused by cancer growth or inflammation. Both are associated with metabolic alterations and, notably, enhancement of the Warburg effect (also known as aerobic glycolysis) of poor efficiency with regard to glucose consumption when compared to mitochondrial respiration. Therefore, beside this efficiency issue, other properties of these two pathways should be considered to explain this paradox: (1) biosynthesis, for this only indirect effect should be considered, since lactate release competes with biosynthetic pathways in the use of glucose; (2) ATP production, although inefficient, glycolysis shows other advantages when compared to mitochondrial respiration and lactate release may therefore reflect that the glycolytic flux is higher than required to feed mitochondria with pyruvate and glycolytic NADH; (3) Oxygen supply becomes critical under hypermetabolic conditions, and the ATP/O2 ratio quantifies the efficiency of oxygen use to regenerate ATP, although aerobic metabolism remains intense the participation of anaerobic metabolisms (lactic fermentation or succinate generation) could greatly increase ATP/O2 ratio; (4) time and space constraints would explain that anaerobic metabolism is required while the general metabolism appears oxidative; and (5) active repression of respiration by glycolytic intermediates, which could ensure optimization of glucose and oxygen use.
Bioenergetics
Warburg Effect
Anaerobic glycolysis
Cellular respiration
Pyruvic acid
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