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Cellular Respiration II Glycolysis, Krebs cycle, Electron transport chain Food Molecules are Broken Down in 3 Stages to Produce ATP Extracellular/ lysosome Cytosol Mitochondria Cellular Respiration  Glycolysis  Krebs Cycle  Electron Transport Chain An overview of cellular respiration Cellular Respiration  Glycolysis  Krebs Cycle  Electron Transport Chain An overview of cellular respiration (Layer 1) No oxygen here! Substrate-level phosphorylation Glycolysis  Glycolysis 3 phases of glycolysis Energy investment 1.   Cleavage 2.   Steps 4-5 6 carbon molecule broken into two 3 carbon molecules of glyceraldehyde-3-phosphate Energy liberation 3.    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 10 A closer look at glycolysis: energy investment phase ENERGY INVESTMENT = 1 ATP! A closer look at glycolysis: energy investment phase ENERGY INVESTMENT = 1 ATP! A closer look at glycolysis: energy payoff phase ENERGY PAYOFF != •2 NADH •2 ATP A closer look at glycolysis: energy payoff phase ENERGY PAYOFF != •2 ATP The energy input and output of glycolysis Glycolysis costs ____ATPs, but makes ___ATPs; thus it has a net yield of ___ATPs. 33% 1. 2. 3. 33% 33% 3, 6, 3 2, 4, 2 4, 8, 4 1 2 3 All of the glycolysis reactions do not require oxygen and can take place in an anaerobic environment. 50% 1. 2. 50% This is true This is false 1 2 During glycolysis, ATP is produced by 1. 2. 3. Oxidative phosphorylation Substrate-level phosphorylation Both of the above 33% 1 33% 2 33% 3 Cellular Respiration  Glycolysis  Krebs Cycle  Electron Transport Chain An overview of cellular respiration Conversion of pyruvate to acetyl CoA, the junction between glycolysis and the Krebs cycle Stage 2: Breakdown of pyruvate to an acetyl group  In eukaryotes, pyruvate in transported to the mitochondrial matrix  Broken down by pyruvate dehydrogenase  Molecule of CO2 removed from each pyruvate  Remaining acetyl group attached to CoA to make acetyl CoA  1 NADH is made for each pyruvate 22 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 + CoA SH CH3 + NAD+ Pyruvate dehydrogenase S CoA C O + CO2 + NADH CH3 Acetyl CoA 23 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 24 Krebs Cycle  Krebs citric acid cycle A closer look at the Krebs cycle A closer look at the Krebs cycle A closer look at the Krebs cycle Flavin Adenine Dinucleotide A closer look at the Krebs cycle A summary of the Krebs cycle Per molecule of glucose X 2! ENERGY PAYOFF != •4 NADH •FADH2 •2 ATP The 2 carbons in acetyl–CoA are eventually used to form — 33% 1. 2. 3. 33% 33% ATP Pyruvate Carbon dioxide 1 2 3 What is the function of the coenzymes, NADH and FADH2 ? 1. 2. 3. Charging electrons to power ATP synthase Catalyzing the formation of acetyl-CoA Providing electrons and H+ to the electron transport chain 33% 1 33% 2 33% 3 What are the main products of the Kreb’s cycle? 1. 2. 3. 4. NADH FADH2 ATP All of the above 25% 1 25% 25% 2 3 25% 4 Cellular Respiration  Glycolysis  Krebs Cycle  Electron Transport Chain An overview of cellular respiration The pathway of electron transport  Collection of molecules in the inner membrane of the mitochondrion 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 37 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 38 The pathway of electron transport  Electrons pass through a series of membrane-associated electron carriers  Flow of electrons along the chain accomplishes the active transport of protons (H+) across the inner mitochondrial membrane  Protons diffuse back into the mitochondrial matrix through a proton channel which couples the diffusion to ATP synthesis Free-energy change during electron transport Ubiquinone Integral membrane proteins Cytochrome C NADH dehydrogenase NADH I H+ H+ H+ KEY NAD+ + H+ Succinate reductase Q Electron transport chain H+ II FADH2 FAD + 2 H+ movement e– movement 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 41 Electron transport  Animation of Electron transport in Mitochondria Proton diffusion is coupled to ATP synthesis Chemiosmosis Chemiosmosis couples the electron transport chain to ATP synthesis Chemiosmosis  Flow of electrons from one electron carrier to another is exergonic  The exergonic reactions drive the endergonic pump of H+ across the mitochondrial membrane  The potential energy of the H+ gradient is used by ATP synthase to generate ATP Figure 9.14 ATP synthase, a molecular mill ATP synthase  Animation of ATP synthesis in Mitochondria ATP synthesis  ATP leaves the mitochondrial membrane as soon as it is made  From one molecule of glucose = 38 ATP molecule (under ideal conditions) Review: how each molecule of glucose yields many ATP molecules during cellular respiration ATP synthase 1. 2. 3. 4. 5. Is an H+ channel Is embedded in the cristae Spins due to the flow of H+ Uses rotational energy to form ATP All of the above 20% 1 20% 20% 2 3 20% 4 20% 5 Cyanide inhibits cytochrome oxidase. Why is this lethal? 1. 2. 3. NAD+ can no longer be reduced to NADH Electron transport chain is shut down Glycolysis is inhibited 33% 1 33% 2 33% 3 The catabolism of various food molecules Control of cellular respiration  Controlled by feedback mechanisms  Feedback inhibition  The end product of the anabolic pathway inhibits the enzyme that catalyzes an early step of the pathway  Phosphofructokinase    Allosteric enzyme Inhibited by ATP Activated by AMP – key step The control of cellular respiration 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 55 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Other acceptors  E. coli uses nitrate (NO3-) under anaerobic conditions  Makes ATP via chemiosmosis even under aerobic conditions KE Y H+ movement e– movement NADH dehydrogenase NADH H+ NAD+ + H+ H+ H+ Ubiquinone H+ Cytochrome b Cytoplasm H+ H+ NO3– + 2 H+ Nitrate reductase H+ NO2– + H2O ADP + Pi ATP H+ 56 H+ ATP synthase H+ Extracellular fluid Fermentation  Fermentation keeps ATP production going when oxygen is unavailable 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 58 Fermentation  Reaction    pathways NADH delivers electrons from glycolysis to organic acceptor molecules converting NADH back to NAD+ Fermentation  NAD+  removed from sugars in glycolysis  ATP  free to accept more electrons production by glycolysis continues in absence of oxygen 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 O— H 2 lactate (secreted from the cell) H C OH C O 2 H+ 2 ethanol (secreted from the cell) (a) Production of lactic acid (b) Production of ethanol (weights): © Bill Aron/Photo Edit; (wine barrels): © Jeff Greenberg/The Image Works 61 2 CO2 H CH3 2 H1 2 NADH CH3 2 acetaldehyde Fermentation Fig. 8-16, p. 173 Cytosol a. Lactate fermentation Glycolysis Glucose Pyruvate Lactate Fig. 8-16a, p. 173 Cytosol b. Alcoholic fermentation Glycolysis Glucose Pyruvate Acetaldehyde Ethyl alcohol Fig. 8-16b, p. 173