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Cells and Their Housekeeping Functions – Metabolic Process and ATP Shu-Ping Lin, Ph.D. Institute of Biomedical Engineering E-mail: [email protected] Website: http://web.nchu.edu.tw/pweb/users/splin/ Date: 11.17.2010 Degradation of Glucose Glucose metabolism: C6H12O6 + 6O2 6CO2 + 6H2O + energy Blocks indicate 4 separate pathways in cellular energy process, each pathway is composed of multiple consecutive reactions catalyzed by enzyme. Anaerobic Respiration Glycolysis in cytoplasm, others in mitochondria (called (Respiration without O2) cellular respiration) Glycolysis: consists of 10 reactions to convert glucose into 2 molecules of 3-carbon compounds (i.e. pyruvic acid and pyruvate) First 5 reactions consume energy: 2 ATP molecules are used to phosphorylate and activate glucose to 3-carbon sugar phosphate Aerobic Respiration nd 2 set of reactions: hydrogen atoms are removed (Respiration using O2) (oxidation) by NAD+ forming NADH (reduction): 2NAD+2 + 4H (oxidation) 2 NADH (that’s a total of 4 e-) -- Four ATP were produced from energy released by substrate-level phosphorylation Exergonic process with ∆G = -140kcal/mol Glycolytic pathway do not involve oxygen Glucose+ 2Pi+ 2ADP+ 2NAD+ 2 pyruvate+ 2ATP+ 2NADH+ 2H++ 2H2O Glycolysis is highly regulated. blood to meet the need for ATP. Cells acquire enough glucose from Citric-Acid Cycle (Aka Krebs Cycle) Begins when acetyl CoA combines with oxaloacetate (a 4-C molecule) to produce citric acid and releases Coenzyme A Each turn of the citric acid cycle consumes one acetyl CoA molecule (originally a pyruvate, since glycolysis produces 2 pyruvates, 1 glucose molecule produces 2 turns of the citric acid cycle ) One turn of the Krebs cycle oxidizes the remaining citric acid, or citrate, producing 1 ATP, 3 NADH, 1 FADH2, and the byproduct 2 CO2 which is exhaled Glucose Metabolism The citric-acid cycle of glucose produces: 4 CO2, 2 ATP, 6 NADH, 2H+, and 2 FADH2 Glucose+ 2Pi+ 2ADP+ 2NAD+ 2 pyruvate+ 2ATP+ 2NADH+ 2H++ 2H2O 2X 2X 2X Respiratory Chain FADH2 & NADH are energy carriers and used to produce ATP. Couple oxidization of NADH or FADH2 to produce ATP 1 NADH H O2 NAD H 2O 2 Intermembrane space G 52.4 Matrix ADP Pi nH P ATP nH N kcal mol Oxidization of NADH by oxygen is exergonic. (Hydrolysis of ATP=-12kcal/mol) Occur on inner membrane of mitochondria (capable of rapid electronexchange, i.e. oxidation & reduction) and involve sequential transfer of electrons through membrane-associated molecules http://www.life.illinois.edu/crofts/bioph354/lect10.html Electron-transport system (ETS): high energy electron-carrying enzyme deliver electrons to more electronegative enzyme Each successive carrier is more electronegative than the last so electrons are pulled downhill One carrier reduces another, energy released is used to pump hydrogen ions across the membrane into the intermembrane space Remaining energy is used to reduce the next carrier ElectonsETSSynthesize ATP Proton (H+) accumulate in the intermembrane space Cause concentration gradient and charge gradient across membrane Concentration gradient forces protons to pass channel protein ATP synthase Relaxation of the proton flux couples formation of ATP. Free-energy change (△G) in transporting uncharged molecule from concentration 1 to 2 is: (R:gas constant=1.987 cal/mol, T:absolute temperature in Kelvin= 273.15 °+ ℃) G RT ln( C 2 ) C1 Membrane electric potential and ion concentration gradient provide driving force for moving ions (charged particles) across membrane. △G of transporting ion might be large enough to drive other processes. (Z:electrical charge of transported species, △V:potential in volts(V) across membrane 12, F:Faraday constant=23.062 kcal/Vmol ) G RT ln( C 2 ) ZFV C1 ATP Synthase ATP synthase catalyzes the formation of ATP Proton-conducting unit F0 spans the lipid bilayer. ATP synthesizing unit F1 faces matrix. Hydrogen flow form intermembrane space to matrix through F0. 3 catalytical β subunits of F1 are structurally identical but in different configurations at any particular point Catalytic site in open (O) form (configuration): little affinity for substrates Loose (L) form: bind to either ATP or ADP+Pi loosely and is catalytically inactive Tight (T) form: bind to either ATP or ADP+Pi tightly and is active Energy input from proton flux converts T site to O site O site to L site L site to T site: New L site binds new ADP and phosphate and begins a new reaction sequence Proton flux: not needed in ATP from ADP+Pi, but can release tightly bound ATP and cycle continues △G<0 in intermembrane space Flow protons through ATPase and ADP+Pi bind to ATPase Enzyme catalyzes formation of ATP ATP detaches from ATP synthase when proton flux http://www.sigmaaldrich.com/life-science/metabolomics/learning-center/metabolic-pathways/atp-synthase.html http://www.sigmaaldrich.com/sigma-aldrich/areas-of-interest/life-science/metabolomics/learning-center/metabolic-pathways/atp-synthase/atp-animation.html Summary of Glycolysis and Cellular Respiration Respiratory Chain: Anaerobic Respiration (Respiration without O2) 4ATP+10NADH + 2FADH2= (4+ 3X10+ 2X2) = 38 ATP Total Yields Aerobic Respiration (Respiration using O2) Mitochondria are highly efficiently as energyprocessing plants. Glucose 2 pyruvates + 2 ATP (in cytoplasm) Pyruvates imported into mitochondrion and oxidized by O2 to produce 30 ATP (3ATPX10=30; since NADH 3ATP molecules, FADH2 2ATP molecules) Photosynthesis Photosynthesis: anabolic reaction, convert light energy to chemical energy of organic compounds – raw materials: water, carbon dioxide (CO2, inorganic) and energy (sunlight) Products: glucose (energy rich carbon compounds) and oxygen (side product) http://en.wikipedia.org/wiki/Photosynthesis 6CO2 + 12H2 O + energy C6H12O6 + 6H2 O + 6O2 H2O: used as reactant and released as a product 2 pathways: driven by light energy in 1st pathway; entrapment of energy received from photons into ATP molecules in subsequent pathway Light: radiant energy (packets of photons) E=h c/ λ (E:energy, c:3x1010cm/s, h:Planck’s constant 1.584x10-34cal s) λ:400~700nm; violet (high “E”), blue, green, yellow, orange, red Energy of molecule absorbing photon rises from ground state to excited state and drives electrons to away from nucleus Loosely held electron then get transferred to other molecules in subsequent reactions, resulting in the production of ATP from ADP Common to the degradation of glucose http://www.overidon.com/wpcontent/uploads/2010/06/wavelength-light1.jpg Common Themes in Metabolic Pathways Central themes of metabolism: 1) 2) 3) 4) ATP is the universal currency of energy. Hydrolysis of ATP increase equilibrium ratio of products to reactants in energy-requiring reaction by a factor of about 108. ATP is generated by the oxidation of fuel molecules such as glucose. Chemical energy in carbon bonds using electron carriers to create proton gradient across inner membrane of mitochondria to synthesize ATP. Metabolic pathways generate ATP and transfer high-potential electrons to electron carriers such as NADH also provide building blocks for macromolecules. Biosynthetic and degradative pathways are almost always separate and utilize different enzymes. Biosynthetic pathway is made exergonic by hydrolysis of ATP. Recurring motifs in these reactions 1) 2) 3) Flow of molecules down metabolic pathway is determined by amounts and activities of certain enzymes. First irreversible reaction in metabolic pathway is committed step Enzymes catalyzing committed steps are typically regulated by the end product. Regulatory enzymes in metabolic pathway are controlled by phosphorylation. Proteosomes control protein concentration by degradation. Metabolic pathways involve compartmentalization of chemical reactions. Whether they are in cytoplasm or in mitochondria, compartmentalization is a useful tool in separating degradative pathways from biosynthetic pathways.