ATP Synthase 1 Outline Proton Mo6ve Force hypothesis ATP synthase Composi6ons how it works P O ra6o and the nal ATP count ShuEle systems Uncouplers of oxida6on phosphoryla6on 2 Oxida6ve Phosphoryla6on 3 Chemiosmo6c Hypothesis By Peter Mitchell 1961 4 Racker and Stoeckenius Con rmed the Mitchell Model 5 ATP Synthase Complex V Intermembrane Space Inner membrane Matrix ATP ADP Pi 6 The F1 Por6on 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 Rota6on of the subunit drives the conforma6onal 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 hEp guweb2 gonzaga edu faculty cronk chemistry chem445 lectures cfm L 6 9 Components of the proton conduc6ng unit of ATP synthase H H H H H H H H H H H H H Asp61 H Asp61 H Matrix half channel 10 Proton path through the membrane H Intermembrane space matrix H H H H H Rota4on driven by proton concentra4on 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 ra6o 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 Oxida6ve Respira6on each NADH 2 5 ATP P O each FADH2 1 5 ATP 15 ATP 3 ATP Grand Total of ATP 30 Will vary between 6ssues 16 How are NADH molecules from Glycolysis moved to Inner Membrane pyruvate 17 Cytosolic NADH can enter the ETC via the Glycerolphosphate ShuEle This shuEle operates in the skeletal muscle and brain Inner mitochondrial membrane 18 Glycerol 3 Phosphate ShuEle 19 Cytosolic NADH enters the ETC via the Malate Aspartate ShuEle aminotransferase aminotransferase This shuEle operates in the liver kidney and heart mitochondria 20 Malate Aspartate ShuEle 21 The rate of oxida6ve respira6on 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 6ssue is revealed on exposure to cold 26 Ac6va6ng Beige Fat An innate immune pathway s6mulates the ac6vity of heat producing adipose 6ssue in mice By Kerry Grens June 5 2014 R R Rao et al Meteorin like is a hormone that regulates immune adipose interac6ons 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 func6onal 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 mo6ve force is converted into ATP Know the two major shuEle systems for electron carriers and the mitochondrial transporters Be able to explain how uncouplers work 29
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