PowerPoint PresentationSlide 2Slide 3Slide 4Racker and Stoeckenius Confirmed the Mitchell ModelSlide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29ATP SynthaseATP Synthase1OutlineOutlineProton-Motive Force hypothesisATP synthase: Compositions, how it works.P/O ratio and the final ATP countShuttle systemsUncouplers of oxidation phosphorylationProton-Motive Force hypothesisATP synthase: Compositions, how it works.P/O ratio and the final ATP countShuttle systemsUncouplers of oxidation phosphorylation2Oxidative PhosphorylationOxidative Phosphorylation3Chemiosmotic HypothesisBy Peter Mitchell (1961)Chemiosmotic HypothesisBy Peter Mitchell (1961)4Racker and Stoeckenius Confirmed the Mitchell ModelRacker and Stoeckenius Confirmed the Mitchell Model5MatrixIntermembrane Space Inner membraneInner membraneATP Synthase / Complex VATP Synthase / Complex VADP + Pi ATP6The F1 Portion of the ATP Synthase behaves as an ATPase when dissociated from the F0 subunit.The F1 Portion of the ATP Synthase behaves as an ATPase when dissociated from the F0 subunit.7LView of the ATP Synthase from the Top (matrix-side)View of the ATP Synthase from the Top (matrix-side)8http://guweb2.gonzaga.edu/faculty/cronk/chemistry/chem445/lectures.cfm?L=6Subunit 1: LTOLTOSubunit 2: OLTOLTSubunit 3: TOLTOLSubunit 1: LTOLTOSubunit 2: OLTOLTSubunit 3: TOLTOLRotation of the γ subunit drives the conformational change of the β subunits.Rotation of the γ subunit drives the conformational change of the β subunits.9Components of the proton-conducting unit of ATP synthaseComponents of the proton-conducting unit of ATP synthaseH+H+H+H+H+H+H+H+H+H+H+H+H+H+H+H+Matrix half-channelH+H+H+H+H+ H+Asp61Asp61H+H+Asp61Asp6110Proton path through the membrane. Proton path through the membrane. Intermembrane spaceIntermembrane spacematrixmatrixH+H+H+H+H+H+Rotation driven by proton concentrationRotation driven by proton concentration11Ferris Wheel at Navy PierFerris Wheel at Navy Pier12The ATP-ADP translocase enables the exchange of cytoplasmic ADP for mitochondrial ATP.The ATP-ADP translocase enables the exchange of cytoplasmic ADP for mitochondrial ATP.13Pi also need to be translocated to the matrixPi also need to be translocated to the matrixGenerates H2O, removing one H+ from Intermembrane space.Adds one proton to the cost of synthesizing each ATP.Generates H2O, removing one H+ from Intermembrane space.Adds one proton to the cost of synthesizing each ATP.matrixmatrixH+ +H2O141 NADH = 10 protons out= 2.5 ATP1 FADH2= 6 protons out = 1.5 ATP1 NADH = 10 protons out= 2.5 ATP1 FADH2= 6 protons out = 1.5 ATPATP synthase :9 subunits uses 9 protons = 3 ATP (3 protons/ATP)Import of 1 Pi : uses 1 proton (1 Pi to make 1 ATP)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 ATPNeed 4 protons to make 1 ATPWhy does FADH2 generate less ATP than NADH2?Why does FADH2 generate less ATP than NADH2?The P/O ratioThe P/O ratio15Pyruvate-AcetylCoA: 2 NADHATP Yield per molecule of glucoseATP Yield per molecule of glucoseGlycolysis: 2 net ATP2 NADHTCA: 2 ATP/GTP6 NADH2 FADH2Oxidative Respiration: each NADH = 2.5 ATP 15 ATPeach FADH2 = 1.5 ATP 3 ATPGrand Total of ATP = 30 3 ATP5 ATP** Will vary between tissues* Will vary between tissuesP/O 16pyruvateHow are NADH molecules from Glycolysis moved to Inner Membrane?How are NADH molecules from Glycolysis moved to Inner Membrane?17Cytosolic NADH can enter the ETC via the Glycerolphosphate ShuttleCytosolic NADH can enter the ETC via the Glycerolphosphate Shuttle This shuttle operates in the skeletal muscle and brain. This shuttle operates in the skeletal muscle and brain.Inner mitochondrial membraneInner mitochondrial membrane18Glycerol 3-Phosphate ShuttleGlycerol 3-Phosphate Shuttle19Cytosolic NADH enters the ETC via the Malate-Aspartate ShuttleCytosolic NADH enters the ETC via the Malate-Aspartate ShuttleThis shuttle operates in the liver, kidney and heart mitochondria.This shuttle operates in the liver, kidney and heart mitochondria.aminotransferaseaminotransferaseaminotransferaseaminotransferase20Malate –Aspartate ShuttleMalate –Aspartate Shuttle21The rate of oxidative respiration is determined by the need for ATPThe rate of oxidative respiration is determined by the need for ATP22The energy charge regulates the use of fuels The energy charge regulates the use of fuels23Uncoupling Protein 1 (UCP-1) / thermogeninUncoupling Protein 1 (UCP-1) / thermogeninMatrixMatrix24Brown FatBrown Fat(Thermogenesis)(Thermogenesis)25Brown adipose tissue is revealed on exposure to cold. Brown adipose tissue is revealed on exposure to cold.26Activating Beige FatAn innate immune pathway stimulates the activity of heat-producing 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, 2014.27Non-physiological chemical uncouplersNon-physiological chemical uncouplersMatrixMatrix2,4,-dinitrophol (DNP)2,4,-dinitrophol (DNP)H+H+H+H+H+28Learning GoalsLearning 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•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
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