PowerPoint PresentationSlide 2Slide 3Slide 4Slide 5Racker and Stoeckenius Confirmed the Mitchell ModelSlide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33Lecture 19 (Ch. 21) – ATP Synthesis•Proton-Motive Force hypothesis•ATP synthase: Compositions, how it works.•P/O ratio and the final ATP count•Shuttle systems•Uncouplers of oxidation phosphorylation1Oxidative Phosphorylation2Chemiosmotic HypothesisBy Peter Mitchell (1961)345Racker and Stoeckenius Confirmed the Mitchell Model6ATP Synthase / Complex VADP + Pi ATP7View 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: TOLTOLRotation of the γ subunit drives the conformational change of the β subunits.91011The F1 Portion of the ATP Synthase behaves as an ATPase when dissociated from the F0 subunit.121314Components of the proton-conducting unit of ATP synthaseH+H+Matrix half-channelH+H+H+H+ H+Asp61H+H+Asp6115Proton path through the membrane. Intermembrane spacematrixRotation driven by proton concentration1617The ATP-ADP translocase enables the exchange of cytoplasmic ADP for mitochondrial ATP18ADP3-cytoplasm + ATP4-matrix ADP3-matrix + ATP4-cytoplasm19ATP-ADP translocase•On Innermembrane•Homodimer•6 transmembrane domains•Binding pocket mostly basic•Antiporter20VDAC (Voltage Dependent Anion Channel•On Outermembrane•Antiparallel Beta-barrel•Open at low or zero membrane potential•Closed by 30-40 mV potential (may be caused by Ca2+ transport)Pi 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.H+ +H2O211 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)Need 4 protons to make 1 ATPWhy does FADH2 generate less ATP than NADH2?The P/O ratio22Pyruvate-AcetylCoA: 2 NADHATP 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 tissuesP/O 23How are NADH molecules from Glycolysis moved to Inner Membrane?24Cytosolic NADH can enter the ETC via the Glycerophosphate Shuttle This shuttle operates in the skeletal muscle and brain25Cytosolic NADH enters the ETC via the Malate-Aspartate ShuttleThis shuttle operates in the liver, kidney and heart mitochondria.aminotransferaseaminotransferase2627Aspartate (Asp) + α-ketoglutarate ↔ oxaloacetate + glutamate (Glu)28The rate of oxidative respiration is determined by the need for ATP29The energy charge regulates the use of fuels30Uncoupling Protein 1 (UCP-1) / thermogenin31Brown Fat and Ucp1Brown fat•Nonshivering thermogenesis•More mitochondria•Mitochondria have UCP1•High in hibernating animals32UCP1•Mitochondrial uncoupling protein•aka Thermogenin•Found in brown adipose tissue•Increases permeability of InnermembraneNon-physiological chemical uncouplers2,4-dinitrophenol
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