Lecture 18 Ch 20 The Electron Transport Chain How do cells oxidize NADH and FADH2 and convert their reducing potential into the chemical energy of ATP Oxidation Reduction reactions Definition of standard reduction potential Organization of the ETC is according to increasing values The components of the mitochondrial ETC The path of e flow and concomitant H transfer in the ETC ROS 1 Overview of the process of complete oxidation of glucose under aerobic conditions Glycolyis TCA Cycle Oxidative Phosphorylation Cellular Respiration generation of Hightransfer potential electron by TCA their flow through respiratory chain and synthesis of ATP 2 Mitochondrial functions are localized in specific compartments eukaryotes Results from Endosymbiotic events most likely from Rickettsia prowazekii pyruvate 3 Cellular Respiration II I IV III 4 5 Reduction of NAD 6 The reduction potential E0 or redox potential is a measure of a molecule s tendency to donate or accept electrons A is getting reduced A is an Oxidizing Agent OA A strong oxidizing agent readily accepts electrons and has a positive redox potential E0 Aox Bred Ared Box Oxidation Loss of eB is getting oxidized B is a Reducing Agent RA A strong reducing agent readily donates electrons and has a negative 7 redox potential E0 Measuring Redox Potential electromotive force oxidized 1 M Fumarate 1 M Succinate reduced Together the oxidized and the reduced forms of the substance are referred to as a redox couple 8 E o Standard Reduction Potential values can be used to predict the direction of redox reactions pH 7 0 The E o std state reduction potential refers to the partial reactions writen as 9 Oxidant e Reductant An Electrochemical Cell E cell Ered Eox E 0 77 V 1 Cu Fe3 Cu2 Fe2 red ox ox red E cell 0 16 0 77 E 0 16 V An Electrochemical Cell Fe2 e Fe3 Cu2 e Cu E cell Ered Eox E 0 77 V 1 Cu Fe3 Cu2 Fe2 red ox ox red E cell 0 16 0 77 E 0 16 V Predict the direction of redox reactions Consider the oxidation of NADH during Oxidative Phosphorylation NADH H O2 NAD H2O red ox ox red This involves the following two half reactions 1 NAD 2e 2H NADH H 2 O2 2H 2e H2O E 0 32 V from table E 0 816 V from table Since we are looking for oxidation of NADH reverse reaction 1 so that it is writen as oxidation Note E 2 E 1 3 NADH H NAD 2H 2e E 0 32 V Now add reactions 2 and 3 to get the overall reaction as writen above NADH H O2 NAD H2O E whole reaction E 2 E 3 0 816 0 32 V 1 136 V 12 Relation between E Std Reduction Potential and G Std State Free Energy of a redox reaction G nF E G is the standard state free energy change of the whole reaction E is the standard state reduction potential difference between the two half cells n F is the number of e transferred is Faraday s constant F 96 500 Coulomb mol or 96500 JV 1mol 1 since 1C 1 JV 1 96 5 kJV 1mol 1 Should be able to calculate G from self calculated given E of a whole redox reaction 13 E Std Reduction Potential values can be used to predict the direction of redox reactions Consider the oxidation of NADH during Oxidative Phosphorylation NADH H O2 NAD H2O red ox ox red E whole reaction 1 136 V G nF E 2 96 5 kJV 1mol 1 1 136 V 219 3 kJ mol large ve value Reaction very spontaneous 14 The Electron Transport Chain also to QH2 pool Does NOT go through II 4 2 X 4 Cyt c Correction Cyt c Is soluble in the intermembrane space NOT the matrix 15 Electrons flow down an energy gradient 16 Complex I NADH Q reductase complex NADH Q 5 H Matrix NAD QH2 4 H intermembrane matrix FMN oxidized flavin mononucleotide 17 Iron sulfur clusters 2Fe 2S cluster 4Fe 4S cluster 18 Complex I NADH Q reductase complex NADH Q 5 H Matrix NAD QH2 4 H intermembrane matrix FMN oxidized flavin mononucleotide 19 Coenzyme Q is derived from isoprene 20 Coenzyme Q Ubiquinone UQ Q10 A mobile e carrier Highly hydrophobic Freely diffuses in the hydrophobic core of the inner mitochondrial membrane 21 CoQ can exist in one of three oxidation states Complex II Succinate Q Reductase complex Succinate Q Fumarate QH2 Succinate dehydrogenase 23 Complex III Q Cytochrome C Oxidoreductase cytochrome C Cyt C Q pool Q QH2 Q pool Q QH2 Ubiquinone matrix 24 Complex III Q Cytochrome C Oxidoreductase cytochrome C Cyt C Q pool Q QH2 Q pool Q QH2 matrix 2H 25 Complex III Q Cytochrome C Oxidoreductase QH2 2 Cyt Cox 2 H Matrix Q 2 Cyt Cred 4 H Intermembrane Q pool Q QH2 Q pool Q QH2 Q pool Q QH2 26 Cytochrome c Structure Oxidized Fe3 Reduced Fe2 27 Complex IV Cytochrome c Oxidase Overview 28 Complex IV Mechanism 29 Complex IV Cytochrome c Oxidase Summary 4 Cyt cred O2 8 H matrix 4 Cyt cox 2 H2O 4 H intermembrane G 231 8 kJ mol 1 30 Oxidative Phosphorylation 4x 4x 2x 31 The Dangerous side to Cellular Respiration Reactive Oxygen Species ROS Free Radicals 2 4 of oxygen molecules consumed by mitochondria are converted into superoxide ions 32 Bad side of ROS Lipid peroxidation membrane damage Polyunsaturated fat only DNA damage 10 000 oxidative hits day Protein oxidation ROS damaged proteins and lipids become reactive radical species themselves and help spread the damage The mutation rate for Mitochondial DNA is 10 20 fold higher than nuclear DNA Due in large part to ROS produced during oxidative phosphorylation 33 ROS plays a role in development of many diseases Heart s disease Cancer Alzheimer s disease Autoimmune diseases lupus rheumatoid arthritis diabetes Adult respiratory distress syndrome Acute renal failure Cerebrovascular injury Alcoholic liver disease Parkinson s disease Aging 34 Three types of Superoxide Dismutase SOD SOD 1 copper zinc dependent in cytosol SOD 2 Manganese dependent in mitochondria SOD 3 Extracellular copper zinc dependent 35 Superoxide Dismutase SOD 2 O2 2 H O2 Step 1 O2 Mox Mred O2 Step 2 H2O2 O2 Mred H2O2 Mox 2H SOD 1 is Deficient in 20 of amyotrophic lateral sclerosis ALS 36 Two enzymes convert Hydrogen Peroxide to H2O In peroxisomes Catalase Glutathione Peroxidase In Cytoplasm 37 GSH Reduced form GS SG Disulfide oxidized form 38 The Glutathione Oxidation Reduction Redox Cycle 39 Other defenses against ROS Vitamin E alpha tocopherol removes covalent links between ROS and faty acid chains Carotenoids Vitamin A lycopene lutein Vitamin C scavenger of a wide variety of ROS Ubiquinol only lipid soluble antioxidant synthesized by human beings Exercise increase SOD 40
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