Electron Transport Chain PKG. 2012

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    Harliansyah, Ph.D

    Human Blok Systems

    Dental Medicine Program

    YARSI UNIVERSITY @ 2012

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    Mitochondria outer membrane relatively permeable

    inner membrane permeable only to those things with

    specific transporters Impermeable to NADH and FADH2 Permeable to pyruvate

    Compartmentalization

    Kreb's and -oxidation in matrix Glycolysis in cytosol

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    Most energy from Redox electrons during metabolic reactions sent to NAD

    and FAD Glycolysis

    In cytosol

    produces 2 NADH

    Pyruvate dehydrogenase reaction In mitochondrial matrix

    2 NADH / glucose Krebs

    In mitochondrial matrix

    6 NADH and 2 FADH2 / glucose

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    Oxidative Level Phosphorylation

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    Electron Transport Chain Groups of redox proteins

    On inner mitochondrial membrane

    Binding sites for NADH and FADH2 On matrix side of membrane

    Electrons transferred to redox proteins

    NADH reoxidized to NAD+

    FADH2

    reoxidized to FAD

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    4 Complexes proteins in specific order

    Transfers 2 electrons in specific order

    Proteins localized in complexes Embedded in membrane

    Ease of electron transfer

    Electrons ultimately reduce oxygen to water

    2 H+

    + 2 e-

    + O2 --

    H2O

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    Electron Transport Chain

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    Complex 1 Has NADH binding site

    NADH reductase activity

    NADH - NAD+

    NADH ---> FMN--->FeS---> ubiquinone

    ubiquinone ---> ubiquinone H2 4 H+ pumped/NADH

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    Electron Transport Chain

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    Complex II succinate ---FADubiquinone

    Contains coenzyme Q

    FADH2 binding site

    FAD reductase activity

    FADH2 -- FAD

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    Electron Transport Chain

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    Complex III ubiquinone - ubiquinone ox

    while cyt C gets reduced

    Also contains cytochromes b proton pump 4H+

    Adds to gradient

    8 H+ / NADH

    4 H+

    / FADH2

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    Electron Transport Chain

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    Complex IV reduction of oxygen

    cytochrome oxidase

    cyt a+a3 red ---> oxidized state oxygen ---> water

    2 H+ + 2 e- + O2 -- 2 H2O

    transfers e- one at a time to oxygen

    Pumps 2H+ out

    Total of 10 H+ / NADH

    Total of 6 H+ / FADH2

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    Totals Proton gradient created as electrons transferred to

    oxygen forming water

    10 H+ / NADH

    6 H+ / FADH2

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    Electron Transport Chain

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    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

    Called chemiosmotic theory

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    ATP

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    Sources of ATP

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    TotalsNADH

    10 H+ X 1 ATP = 2.5 ATP

    4 H

    +

    FADH2

    6 H+X 1 ATP = 1.5 ATP

    4 H+

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    Total ATP from mitochondrial matrix Pyruvate dehydrogenase

    NADH .2.5 ATP

    Krebs3 NADH X 2.5 ATP/NADH .7.5 ATP

    FADH2 X 1.5 ATP / FADH2.1.5 ATP

    GTP X 1 ATP / GTP ..1.0 ATP(from a separate reaction)

    Total .12.5 ATP

    (Per glucose = X 2 = 25 ATP)

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    Review of ATP Production

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    What about NADH from glycolysis? NADH made in cytosol

    Cant get into matrix of mitochondrion

    2 mechanisms In muscle and brain

    Glycerol phosphate shuttle

    In liver and heart

    Malate / aspartate shuttle

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    Glycerol Phosphate shuttle

    http://courses.cm.utexas.edu/jrobertus/ch339k/overheads-3/ch19_glycerol-shuttle.jpg

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    Glycerol phosphate shuttle In muscle and brain

    Each NADH converted to FADH2 insidemitochondrion

    FADH2 enters later in the electron transport chain

    Produces 1.5 ATP

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    Total ATP per glucose in muscle and brain Gycerol phosphate shuttle

    2 NADH per glucose - 2 FADH2

    2 FADH2

    X 1.5 ATP / FADH2.3.0 ATP

    2 ATP in glycoysis 2.0 ATP

    From pyruvate and Krebs

    12.5 ATP X 2 per glucose ..25.0 ATP

    Total = 30.0 ATP/ glucose

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    Malate Aspartate Shuttle

    http://courses.cm.utexas.edu/emarcotte/ch339k/fall2005/Lecture-Ch19-2/Slide14.JPG

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    Malate Aspartate Shuttle

    in cytosol In liver and heart

    NADH oxidized while reducing oxaloacetate to malate

    Malate dehydrogenase Malate crosses membrane

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    Malate Aspartate Shuttle

    in matrix Malate reoxidized to oxaloacetate

    Malate dehydrogenase

    NAD+

    reduced to NADH NADH via electron transport yields 2.5 ATP

    Mlate Aspartate

    Shuttle

    in cytosol

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    Total ATP per glucose in liver and heart Malate Aspartate Shuttle

    2 NADH per glucose - 2 NADH

    2 NADH X 2.5 ATP / NADH5.0 ATP

    2 ATP from glycolysis..2.0 ATP

    From pyruvate and Krebs

    12.5 ATP X 2 per glucose ..25.0 ATP

    Total = 32.0 ATP/ glucose

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    Summary Total ATP / glucose

    Muscle and brain 30.0 ATP Uses glycerol phosphate shuttle

    Heart and liver 32.0 ATP Uses malate aspartate shuttle