ATP Synthase 1 Outline Proton Motive Force hypothesis ATP synthase Compositions how it works P O ratio and the final ATP count Shuttle systems Uncouplers of oxidation phosphorylation 2 Oxidative Phosphorylation 3 Chemiosmotic Hypothesis By Peter Mitchell 1961 4 Racker and Stoeckenius Confirmed the Mitchell Model 5 ATP Synthase Complex V Intermembrane Space Inner membrane Matrix ATP ADP Pi 6 The F1 Portion of the ATP Synthase behaves as an ATPase when dissociated from the F0 subunit 7 View of the ATP Synthase from the Top matrix side L 8 Rotation of the subunit drives the conformational change of the subunits Subunit 1 L T O L T O Subunit 2 O L T O L T Subunit 3 T O L T O L http guweb2 gonzaga edu faculty cronk che mistry chem445 lectures cfm L 6 9 Components of the proton conducting unit of ATP synthase H H H H H H H H H H H H H Asp61 H Asp61 H Matrix halfchannel 10 Proton path through the membrane H Intermembrane space matrix H H H H H Rotation driven by proton concentration 11 Ferris Wheel at Navy Pier 12 The ATP ADP translocase enables the exchange of cytoplasmic ADP for mitochondrial ATP 13 Pi also need to be translocated to the matrix Generates H2O removing one H from Intermembrane space Adds one proton to the cost of synthesizing each ATP H2O H matrix 14 Why does FADH2 generate less ATP than NADH2 ATP synthase 9 subunits uses 9 protons 3 ATP 3 protons ATP Import of 1 Pi uses 1 proton 1 Pi to make 1 ATP Need 4 protons to make 1 ATP 1 NADH 10 protons out 2 5 ATP The P O ratio 1 FADH2 6 protons out 1 5 ATP 15 ATP Yield per molecule of glucose Glycolysis 2 net ATP 2 NADH 3 ATP Pyruvate AcetylCoA 2 NADH 5 ATP TCA 2 ATP GTP 6 NADH 2 FADH2 Oxidative Respiration P O each NADH 2 5 ATP each FADH2 1 5 ATP 15 ATP 3 ATP Grand Total of ATP 30 Will vary between tissues 16 How are NADH molecules from Glycolysis moved to Inner Membrane pyruvate 17 Cytosolic NADH can enter the ETC via the Glycerolphosphate Shuttle This shuttle operates in the skeletal muscle and brain Inner mitochondrial membrane 18 Glycerol 3 Phosphate Shuttle 19 Cytosolic NADH enters the ETC via the Malate Aspartate Shuttle aminotransferase aminotransferase This shuttle operates in the liver kidney and heart mitochondria 20 Malate Aspartate Shuttle 21 The rate of oxidative respiration is determined by the need for ATP 22 The energy charge regulates the use of fuels 23 Uncoupling Protein 1 UCP 1 thermogenin Matrix 24 Brown Fat Thermogenesis 25 Brown adipose tissue is revealed on exposure to cold 26 Activating Beige Fat An innate immune pathway stimulates the activity of heatproducing adipose tissue in mice By Kerry Grens June 5 2014 R R Rao et al Meteorin like is a hormone that regulates immune adipose interactions to increase beige fat thermogenesis Cell doi 10 1016 j cell 2014 03 065 2014 Y Qiu et al Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat Cell doi 10 1016 j cell 2014 03 066 2014 27 Non physiological chemical uncouplers 2 4 dinitrophol DNP H H H H H Matrix 28 Learning Goals Be able to describe how the proton motive force is converted into ATP Know the two major shuttle systems for electron carriers and the mitochondrial transporters Be able to explain how uncouplers work 29
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