Electron Transport Chain TAU PDF

Medical Biochemistry (MBG1125) Electron Transport Chain “It all reduces down to Water” by Dr. Chimuka Mwaanga Electron Transport Chain (Outline) Overview Sequence of electron transport and carriers Oxidative phosphorylation Inhibitors of electron transport c...

Medical Biochemistry (MBG1125) Electron Transport Chain “It all reduces down to Water” by Dr. Chimuka Mwaanga Electron Transport Chain (Outline) Overview Sequence of electron transport and carriers Oxidative phosphorylation Inhibitors of electron transport chain Uncouplers Regulation of the electron transport chain Mitochondrion: The Power House of The Cell Mitochondria outer membrane relatively permeable inner membrane permeable only to those metabolites with specific transporters Impermeable to NADH and FADH2 Permeable to pyruvate Compartmentalization Kreb's cycle and β-oxidation in matrix Electron transport chain on inner membranes Glycolysis in cytosol  In Cytosol Stages of Cellular Respiration C6H12O6 + 6O2 6CO2 + 6H2O + ATP In Mitochondria Step 3: Electron transport chain and oxidative phosphorylation 28 32 Step 3: Electron transport chain and oxidative phosphorylation 90% of energy is from oxidation of NADH and FADH2 Electrons during metabolic reactions are sent to NAD + and FAD Glycolysis In cytosol produces 2 NADH Pyruvate dehydrogenase reaction In mitochondrial matrix 2 NADH per glucose TCA cycle In mitochondrial matrix 6 NADH and 2 FADH2 per glucose Electron Transport Chain and Oxidative Phosphorylation  Electron Transport Chain During electron transport, energy released is used to transport H+ across the Fig. 16-19 inner mitochondrial membrane to create an electrochemical gradient Electron transport chain inhibitors Antimycin A rotenone Sodium azide CN CO Fig. 16-19 Oxidative Phosphorylation Oxidative phosphorylation is the process by which the energy stored in NADH and FADH2 is used to produce ATP. A. Oxidation step: electron transport chain 1 NAD+ + H2O NADH + H+ + O 2 2 1 FADH2 + O2 FAD + H2O 2 B. Phosphorylation step ADP + Pi ATP Oxidative Phosphorylation H+ transport results in an electrochemical gradient Proton motive force: energy released by flow of H+ down its gradient is used for ATP synthesis ATP synthase: H+ channel that couples energy from H+ flow with ATP synthesis ATP synthase 4 Protons are needed / 1 ATP synthesis Intermembrane space 4H+ 4H+ 2H+ 4H+ Complex I Complex III Complex IV 2e- 2e- 2e- Complex II NADH NAD+ FAD 1/2O2 + 2H+ + 2e- H2O FADH2 Matrix ADP + Pi ATP 4H+  Energy Calculations NADH 10 H+ X 1 ATP = 2.5 ATP 4 H+ FADH2 6 H+ X 1 ATP = 1.5 ATP 4 H+ Generation of ATP Proton dependant ATP synthetase Uses proton gradient to make ATP Protons pumped through channel on enzyme From intermembrane space into matrix ~4 H+ / ATP The process is called chemiosmotic theory  ATP Synthesis by ATP-synthase ATP uses the energy of an existing proton gradient to power ATP synthesis. This proton gradient develops between the intermembrane space and the matrix. This concentration of H+ is the proton-motive force ▪ The ATP synthase molecules are the only places that will allow H+ to diffuse back to the matrix (exergonic flow of H +). ▪ This flow of H+ is used by the enzyme to generate ATP through a process called chemiosmosis. Inhibitors and uncouplers of oxidative phosphorylation Inhibitors Atractyloside: ADP/ATP antiporter Atractyloside Oligomycin: ATP synthase oligomycin Uncouplers DNP DNP shuttles H+ across inner membrane, dissipates gradient ETC & Oxidative Phosphorylation inhibitors What about NADH from glycolysis? NADH made in cytosol can’t get into matrix of mitochondrion 2 mechanisms that transfer electrons from cytosolic NADH exists; In muscle and brain Glycerol phosphate shuttle In liver and heart Malate / aspartate shuttle Glycerol 3-Phosphate shuttle Glycerol phosphate shuttle Glycerol phosphate shuttle takes place in muscle and brain Each NADH is converted to FADH2 inside mitochondrion FADH2 enters later in the electron transport chain FADH2 produces 1.5 ATP Malate – Aspartate Shuttle Malate – Aspartate Shuttle Malate – Aspartate Shuttle Takes place in liver and heart NADH oxidized while reducing oxaloacetate to malate Malate dehydrogenase Malate crosses inner membrane into the matrix where it passes the electrons back to NAD+ producing NADH Malate – Aspartate Shuttle in matrix Malate gets reoxidized to oxaloacetate Malate dehydrogenase NAD+ reduced to NADH NADH via electron transport yields 2.5 ATP Summary Total ATP / glucose produced in; Muscle and brain 30.0 ATP Uses glycerol phosphate shuttle Heart and liver 32.0 ATP Uses malate aspartate shuttle