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CHAPTER 7 LECTURE SLIDES Prepared by Brenda Leady University of Toledo To run the animations you must be in Slideshow View. Use the buttons on the animation to play, pause, and turn audio/text on or off. Please note: once you have used any of the animation functions (such as Play or Pause), you must first click in the white background before you advance the next slide. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cellular respiration Process by which living cells obtain energy from organic molecules Primary aim to make ATP and NADH Aerobic respiration uses oxygen O2 consumed and CO2 released Focus on glucose but other organic molecules also used 2 Glucose metabolism 1. 2. 3. 4. C6H12O6 + 6O2 → 6CO2 + 6H2O 4 metabolic pathways Glycolysis- Substrate level phosphorylation Breakdown of pyruvate to an acetyl group Citric acid cycle Oxidative phosphorylation 3 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1 Glycolysis: Glucose C C C C C C Outer mitochondrial membrane Cytosol 2 pyruvate 2 C C C 2 NADH Mitochondrial matrix Inner mitochondrial membrane 2 NADH 2 pyruvate 2 Breakdown of pyruvate: 2 pyruvate 2 C C C 2CO2 + 2acetyl 6 NADH 2 FADH2 3 Citric acid cycle: 2 acetyl 4 Oxidative 2 C C 2 C C 2 CO2 2 CO2 +2 ATP Via substrate-level phosphorylation 2 acetyl 4 CO2 2 CO2 +2 ATP Via substrate-level phosphorylation phosphorylation: The oxidation of NADH and FADH2 via the electron transport chain provides energy to make more ATP via the ATP synthase. O2 is consumed. +30–34 ATP Via chemiosmosis 4 Stage 1: Glycolysis Glycolysis can occur with or without oxygen Steps in glycolysis nearly identical in all living species 10 steps in 3 phases Energy investment 2. Cleavage 3. Energy liberation 1. 5 Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 6 3 phases of glycolysis 1. Energy investment 2. Cleavage 3. Steps 4-5 6 carbon molecule broken into two 3 carbon molecules of glyceraldehyde-3-phosphate Energy liberation Steps 1-3 2 ATP hydrolyzed to create fructose-1,6 bisphosphate Steps 6-10 Two glyceraldehyde-3-phosphate molecules broken down into two pyruvate molecules producing 2 NADH and 4 ATP Net yield in ATP of 2 7 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. C C C C C C CH2OH O H H H OH H HO OH H OH Glucose 8 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Energy investment phase C C C C C C C C C C C C CH2OH O H H H OH Step 2 Step 3 H HO OH H Step 1 OH Glucose P OCH2 H ATP H CH2O P O HO OH ATP OH H Fructose-1,6bisphosphate 9 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Energy investment phase Cleavage phase C C C H Step 4 Step 5 C O CHOH C C C C C C C C C C C C CH2O P CH2OH O H H H OH Step 2 Step 3 H HO OH H Step 1 OH Glucose P OCH2 H ATP H CH2O P O HO OH ATP OH H Fructose-1,6bisphosphate C C C H C O CHOH CH2O P Two molecules of glyceraldehyde3-phosphate 10 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Energy investment phase Cleavage phase Energy liberation phase C C C C C C O– H Step 4 Step 5 C O Step 6 Step 7 Step 8 Step 9 Step 10 C O C O CHOH C C C C C C C C C C C C CH2O P CH2OH Pi O H H H OH Step 2 Step 3 H HO OH H Step 1 OH Glucose P OCH2 H ATP H ATP ATP CH3 CH2O P O HO OH ATP OH NADH H Fructose-1,6bisphosphate C C C C C C O– H C O CHOH CH2O P Pi Two molecules of glyceraldehyde3-phosphate NADH ATP ATP C O C O CH3 Two molecules of pyruvate 11 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. O– C O C O Outer CH3 membrane channel O– H+/pyruvate C O symporter H+ C O CH3 + CoA SH + NAD+ Pyruvate dehydrogenase S CoA C O + CO2 + NADH CH3 Acetyl CoA 12 Stage 3: Citric acid cycle Metabolic cycle Particular molecules enter while other leave, involving a series of organic molecules regenerated with each cycle Acetyl is removed from Acetyl CoA and attached to oxaloacetate to form citrate or citric acid Series of steps releases 2CO2, 1ATP, 3NADH, and 1 FADH2 Oxaloacetate is regenerated to start the cycle again 13 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glycolysis: Glucose 2 NADH 2 NADH 6 NADH Citric acid cycle 2 pyruvate 2 CO2 2 CO2 Breakdown of pyruvate +2 ATP 2 FADH2 Oxidative phosphorylation NADH CO2 2 CO2 +2 ATP Citrate +30–34 ATP NADH C C C C C C C C C C C C CO2 3 2 C C C C C 4 1 C C C C Citric acid cycle O C C C C 5 Oxaloacetate H2C C S CoA Acetyl CoA 8 C C C C 7 NADH 6 C C C C GTP C C C C ATP FADH2 14 Stage 4: Oxidative phosphorylation High energy electrons removed from NADH and FADH2 to make ATP Typically requires oxygen Oxidative process involves electron transport chain Phosphorylation occurs by ATP synthase 15 Oxidation: ETC Electron transport chains (ETC) Group of protein complexes and small organic molecules embedded in the inner mitochondrial membrane Can accept and donate electrons in a linear manner in a series of redox reactions Movement of electrons generates H+ electrochemical gradient/ proton-motive force Excess of positive charges outside of matrix 16 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. KEY H+ movement e– movement Matrix Intermembrane space NADH dehydrogenase NADH I H+ H+ H+ NAD+ + H+ Succinate reductase Q Electron transport chain H+ II FADH2 FAD + 2 Ubiquinone H+ H+ H- Cytochrome b-c1 III H+ H+ Cytochrome c c H+ H+ 2 H+ + ½ O2 IV Cytochrome oxidase H+ H+ H2O H+ Matrix H+ ATP synthase H+ ADP + Pi H+ ATP Inner mitochondrial membrane ATP synthesis H+ Intermembrane space 17 Phosphorylation: ATP synthase Lipid bilayer of inner mitochondrial membrane relatively impermeable to H+ Can only pass through ATP synthase Harnesses free energy release to synthesize ATP from ADP Chemiosmosis- chemical synthesis of ATP as a result of pushing H + across a membrane 18 NADH oxidation and ATP synthesis Oxidation of NADH results in electrochemical gradient used to synthesize ATP 30-34 ATP molecules per glucose molecule broken down into CO2 and H2O Rarely achieve maximal amount NADH used in anabolic pathways H+ gradient used for other purposes 19 ATP synthase Enzyme harnesses free energy as H+ flow through membrane embedded region Energy conversion- H+ electrochemical gradient or proton motive force converted to chemical bond energy in ATP Racker and Stoeckenius confirmed ATP uses an H+ electrochemical gradient Rotary machine that makes ATP as it spins 20 Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 21 Cancer cells usually favor glycolysis Many disease associated with alterations in carbohydrate metabolism Warburg effect- cancer cells preferentially use glycolysis while decreasing oxidative phosphorylation Used to diagnose cancers in PET scans Glycolytic enzymes overexpressed in 80% of all types of cancers Caused by genetic and environmental factorsmutations and low oxygen Other organic molecules Focus on glucose but other carbohydrates, proteins and fats also used for energy Enter into glycolysis or citric acid cycle at different points Utilizing the same pathways for breakdown increases efficiency Metabolism can also be used to make other molecules (anabolism) 24 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Proteins Amino acids Carbohydrates Sugars Fats Glycerol Fatty acids Glycolysis: Glucose Glyceraldehyde3-phosphate Pyruvate Acetyl CoA Citric acid cycle Oxidative phosphorylation © The McGraw-Hill Companies, Inc./Ernie Friedlander/Cole Group/Getty Images 25 Anaerobic metabolism For environments that lack oxygen or during oxygen deficits 2 strategies Use substance other than O2 as final electron acceptor in electron transport chain Produce ATP only via substrate-level phosphorylation 26 Fermentation Many organisms can only use O2 as final electron acceptor Make ATP via glycolysis only Need to regenerate NAD+ to keep glycolysis running Muscle cells produce lactate Yeast make ethanol Produces far less ATP 27 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2 ADP + 2 Pi 2 ATP O— 2 ADP + 2 Pi 2 ATP C O C O C O C O Glucose Glycolysis Glucose CH3 Glycolysis CH3 2 pyruvate 2 pyruvate O— 2 NAD+ + 2 H+ 2 NAD+ + 2 H+ 2 NADH C O H C OH CH3 H 2 H1 2 lactate (secreted from the cell) (a) Production of lactic acid O— 2 NADH 2 CO2 H H C OH C O CH3 2 H+ 2 ethanol (secreted from the cell) CH3 2 acetaldehyde (b) Production of ethanol (weights): © Bill Aron/Photo Edit; (wine barrels): © Jeff Greenberg/The Image Works 28