Module9LIFE210.pdf LIFE 210
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This 4 page Class Notes was uploaded by Mikaela Maldonado on Friday October 23, 2015. The Class Notes belongs to LIFE 210 at Colorado State University taught by Paul J Laybourn in Fall 2015. Since its upload, it has received 21 views. For similar materials see Introductory Eukaryotic Cell Biology in Entomology at Colorado State University.
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Date Created: 10/23/15
The Warburg Effect gt First describe by Otto Warburg and coworkers in 1927 gt Tumor and cancer cells I Increased glucose uptake and lactate production relative to normal cells I With normal oxygen level high respiration I High glutamine dependency Natural location in blood gt Termed aerobic glycolysis I Better term might be anaerobic glycolysis in presence of normal oxygen levels In the brain astrocytes and neuronal cells form a commensal metabolic relationship gt Astrocytes eat glucose Warburg effect glucosegtlactate gt Neurons import lactate use for oxidative phosphorylation lactate neurons eat Pyruvate AcCoA C02 gt Neurons also convert glutamine to glutamate release as a neurotransmitter I Too much glutamate causes a stroke by over excitement of surrounding cells gt Astrocytes convert glutamate back to glutamine because too much is toxic Early embryogenesis gt First 3 cell division aerobic glycolysis gt After that use both aerobic glycolysis and oxidative phosphorylation gt Embryonic cells also use glutamine to full up the TCA cycle and produce amino acids Radiolabeled 18fluoro2deoxyglucose in positron emission tomography PET gt Shows high glucose uptake in cancer cells compared to normal cells gt Have found cancer cells also need a lot of glutamine gt Cancer cells have change that short circuit the normal inhibition of of glycolysis at normal 02 levels gt Tumor cells with poor blood supply and low oxygen appear to have a commensal relationship with other cancer or normal cells with adequate oxygen gt Cancer cells with aerobic glycolysis also have high oxidative phosphorylation levels gt Cancer cells rely on glutamine for filling up the TCA cycle and producing animo acids etc gt More research is needed to better understand the other metabolic change that occur in cancerceHs High glucose metabolism in cancer cells gt PET scan overlaid on CT scan gt Show radioactive fluorine is CT scan shows the tissues and orientation of things within the body CLICKER QUESTION Aerobic glycolysis or the Warburg effect gt Can be visualized through PET scans gt Is only seen in cancer cells Targeting cancer cells through the Warburg effect gt Cancer cells vs normal cells have unregulated growth and cell division I Independent of actual nutrient supply I Addicted to nutrient Achilles heel I If nutrients inadequate I Autophagy I Cell death I So key metabolic enzyme inhibitors could be effective anticancer drugs Glutamine converts through the citric acid cycle and glucose is converted through glycolysis CLICKER 3 bromopyruvate BrPA inhibits hexokinase and glyceraldehyde 3P dehydrogenase The data suggests I Cancer cells can be killed by targeting fatty acid synthesis I All cancer cells are killed by BrPA I Some cancer cells are highly dependent on glycolysis for ATP production I Metabolic changes are not a promising avenue for design of anticancer therapies I Targeting gluconeogenesis enzymes with inhibitor is effective in killing cancer cells Drugs that inhibit metabolic enzymes have promise as anticancer therapies Like other change in cancer cells the metabolic changes in specific cancer types and individual cancer will vary Therefore characterization of metabolic profiles of cancer types Metabolism gt Catabolic I nutrient degradation oxidation I Produce ATP I Glucose to pyruvate I exergonic Anabolic I Biosynthesis reduction I Requireuse ATP I Glutamate to glutamine I endergonic Amphibolic I Pathways that can do both Potential energy I Nutrient in the environment complex molecule such as sugars fats I Suanht Energy transductions accomplish work I Chemical transformation within cells Cellular work in a positive G O Chemical synthesis Mechanical work Osmotic and electrical gradients Light production Genetic information transfer Heat Increase randomness or entropy in the surroundings 0000 O 09 O 09 O Metabolism produces compounds simpler than the initial fuel molecule C02 NH3 H20 HPO4 Decreased randomness in the system Q Simple compound polymerize to form informationrich macromolecules DNA RNA proteins I Cells are an open system CLICKER 1 Living organisms require a continual supply of energy to exist because gt They defy the laws of thermodynamics gt They convert it into hear energy which powers biosynthetic reactions gt They are creating order out of disorder inside their cells gt They are causing the entropy in the universe to decrease gt They are close systems isolated from the rest of the universe The Cell Inc gt Manufacturing company walls are the plasma membrane I DNA top management in the nucleus decide what the company is I RNA middle management communicates instructions from the top management to the staffworkers gt Two main types of function in the cell I Making things anabolism say bicycles I Obtaining capital finances and raw materials catabolism money metals plastic paint etc I The internal quotcurrencyquot of the cell connecting finances and making thins anabolism and catabolism is ATP and NADH gt Goals I Manufacture products macromolecules I Ultimately to make a whole new factory cell I When plenty of capital and raw materials high energy food high levels of manufactory rapid growth I When capital and raw materials are short low energy food low levels of manufacturing slow growth I Regulationcontrol needed to tire the rate of growth to the situation I Cancer uncontrolled growth poor management finances and manufacturing out of balance cannibalizing department lay offs cell all nucleus recession cancer Additional general features of metabolism gt Metabolism is in a steady state far from equilibrium gt Especially the energy currencies I Nutrients are used to obtain building blocks and to produce energy ATP energy currency O ATPH20gtADPPiH O Kidney cell ADPATP 110 O Muscle cell ADPATP15 O Pi 1100 NAdPH energy currency reductionoxidation O 0 Oxidation and Reduction of Cellular Molecules O Oxidation loss of e Reduction gain of e ATP hydrolysis Couple reactions O Require E input or spontaneous in reverse O Biosynthesis gt ADP PgtATP gt AA to proteins gt NTPS to DNA gt Cell organelle movement gt All have a delta G I Metabolism consists of pathways of reactions Catalyzed by enzymes Allows reactions to be couples to energy currency production and use catabolism and anabolism Enzymes can be regulated to keep catabolism and anabolism balance keep ATPADP Pi far from equilibrium Under most conditions the supply of energy by catabolic pathways is regulated by the demand for energy by anabolic pathways Considering the role of ATP formation and hydrolysis in energy coupling of anabolic and catabolic pathways which of the following statement is most likely to be true gt High levels of ADP act as an inhibitor of catabolic pathways High levels of ATP act as an activator of anabolic pathways High levels of ATP act as an activator of catabolic pathways High levels of ADP act as an activator of catabolic pathways High levels of ADP act as an inhibitor of anabolic pathways ATP occurs as the regulatory molecule not ADP I Glucose oxidation is couple to ATP NADH production CLICKER 3 The advantage to a cell of the gradual oxidation of glucose during cellular respiration compared with its combustion to C02 and H20 in a single step is gt More free energy is released for a given amount of glucose oxidized gt No energy is lost as heat gt Energy can be extracted in usable amounts gt More C02 is produced for a given amount of glucose oxidized gt Less 02 is required for a given amount of glucose oxidized When 1 mole of ATP is hydrolyzed in a test tube without an enzyme about twice as much heat is given off as when 1 mole ATP is hydrolyzed in a cell The observation are best explained by gt The hydrolysis of ATP is coupled to other endergonic reactions gt gt gt gt