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  • Lec 17 (Ch. 14) Oxidative Phosph

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    Ramy El-Hadad
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    This document discusses electron transport and oxidative phosphorylation. It describes how electrons are passed through protein complexes in the inner mitochondrial membrane to generate a proton gradient. This proton gradient then drives the synthesis of ATP through oxidative phosphorylation. The protein complexes, electron carriers, inhibitors, and coupling of electron transport to ATP synthesis are covered in detail. The ratio of ATP produced per electron pair (the P/O ratio) depends on which electron donors are used.

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    This document discusses electron transport and oxidative phosphorylation. It describes how electrons are passed through protein complexes in the inner mitochondrial membrane to generate a proton gradient. This proton gradient then drives the synthesis of ATP through oxidative phosphorylation. The protein complexes, electron carriers, inhibitors, and coupling of electron transport to ATP synthesis are covered in detail. The ratio of ATP produced per electron pair (the P/O ratio) depends on which electron donors are used.

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    © All Rights Reserved
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    25 views40 pages

    Lec 17 (Ch. 14) Oxidative Phosph

    Uploaded by

    Ramy El-Hadad
    This document discusses electron transport and oxidative phosphorylation. It describes how electrons are passed through protein complexes in the inner mitochondrial membrane to generate a proton gradient. This proton gradient then drives the synthesis of ATP through oxidative phosphorylation. The protein complexes, electron carriers, inhibitors, and coupling of electron transport to ATP synthesis are covered in detail. The ratio of ATP produced per electron pair (the P/O ratio) depends on which electron donors are used.

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    of 40

    Electron Transport and

    Oxidative Phosphorylation

    DR. REEM ARAFA

    All rights reserved. Requests for permission to make copies of any part of the work
    should be mailed to: Permissions Department, Harcourt Brace & Company, 6277
    Sea Harbor Drive, Orlando, Florida 32887-6777
    An Overview
    ► Electron Transport: Electrons carried by reduced
    coenzymes are passed through a chain of
    proteins and coenzymes to drive the generation
    of a proton gradient across the inner
    mitochondrial membrane

    ► Oxidative Phosphorylation: The proton gradient


    runs downhill to drive the synthesis of ATP

    ► It all happens in or at the inner mitochondrial


    membrane
    21.2 Reduction Potentials
    High positive Eo' indicates a strong affinity for electrons and a
    hightendency to be reduced
    ► Crucial equation: ΔGo' = -nF ΔEo'

    ► ΔEo' = Eo'(acceptor) - Eo'(donor)

    ► Electrons are donated by the half reaction with the more


    negative reduction potential and are accepted by the
    reaction with the more positive reduction potential: ΔEo’
    positive, ΔGo' negative

    ► If a given reaction is written so the reverse is true, then the


    ΔEo' will be a negative number and ΔGo' will be positive
    21.3 Electron Transport

    ► Four protein complexes in the inner


    mitochondrial membrane

    ► A lipid soluble coenzyme (UQ, CoQ) and a water


    soluble protein (cyt c) shuttle between protein
    complexes

    ► Electrons generally fall in energy through the


    chain - from complexes I and II to complex IV
    ETC and the oxphos

    H++ H+++
    HH H
    H+
    OUT Cyt
    - C- Cyt
    - C-
    ee ee
    e- Q e- e-

    IN
    e- e- + +
    H2OH
    H - O OHH++H
    H H2O
    - ++
    H
    H+H+ O22
    H NAD+
    +`+` +
    HH
    ADP ATP

    NADH TCA
    Cycle

    Peter S. Rabinwitch after Mandavilli et al, Mutation Research 509 (2002) 127–151
    21.4 Complex I
    NADH-CoQ Reductase
    ► Electron transfer from NADH to CoQ

    ► More than 30 protein subunits - mass of 850 kD

    ► Path:
    ► NADH → FMN → Fe-S → UQH2→ Fe-S → UQH2

    ► 4H+ transported out per 2e-


    21.5 Complex II
    Succinate-CoQ Reductase
    ► aka succinate dehydrogenase (from TCA cycle!)

    ► aka flavoprotein 2 (FP2) - FAD covalently bound

    ► four subunits, including 2 Fe-S proteins

    ► Path: succinate → FADH2 → 2Fe2+ → UQH2


    ► Net reaction:
    ► succinate + UQ → fumarate + UQH2
    21.6 Complex III
    CoQ-Cytochrome c Reductase

    ► CoQ passes electrons to cyt c (and pumps H+) in a


    unique redox cycle known as the Q cycle

    ► Cytochromes, like Fe in Fe-S clusters, are one-


    electron transfer agents

    ► UQH2 is a lipid-soluble electron carrier

    ► cyt c is a water-soluble electron carrier


    21.7 Complex IV
    Cytochrome c Oxidase

    ► Electrons from cyt c are used in a four-electron


    reduction of O2 to produce 2H2O

    ► Oxygen is thus the terminal acceptor of


    electrons in the ETC - the end!

    ► Complex IV also transports H+


    -
    Coupling e Transport and
    Oxidative Phosphorylation
    This coupling was a mystery for many years

    ► Many biochemists wasted careers searching for the


    elusive "high energy intermediate"

    ► Peter Mitchell proposed a novel idea - a proton


    gradient across the inner membrane could be used
    to drive ATP synthesis

    ► Mitchell was ridiculed, but the chemiosmotic


    hypothesis eventually won him a Nobel prize
    21.9 ATP Synthase

    Proton diffusion through the protein drives


    ATP synthesis!

    ► Two parts: F1 and F0 (latter was originally "F-o" for


    its inhibition by oligomycin)

    ► Racker & Stoeckenius confirmed Mitchell’s


    hypothesis using vesicles containing the ATP
    synthase and bacteriorhodopsin
    21.10 Inhibitors of
    Oxidative Phosphorylation
    ► Rotenone inhibits Complex I - and helps natives of
    the Amazon rain forest catch fish!

    ► Cyanide, azide and CO inhibit Complex IV,


    binding tightly to the ferric form (Fe3+)

    ► Oligomycin is an ATP synthase inhibitors


    Cyanide
    Antimycin A
    Azide, CO Oligomycin
    Rotenone H+

    FCCP
    (or DNP)
    21.11 Uncouplers
    Uncoupling e- transport and oxidative
    phosphorylation

    ► Uncouplers disrupt the tight coupling between


    electron transport and oxidative phosphorylation by
    dissipating the proton gradient

    ► Uncouplers are hydrophobic molecules with a


    dissociable proton

    ► They shuttle back and forth across the membrane,


    carrying protons to dissipate the gradient
    Antimycin A Azide Oligomycin
    Rotenone H+

    FCCP
    (or DNP)
    21.12 ATP-ADP Translocase
    ATP must be transported out of the mitochondria
    ► ATP out, ADP in - through a "translocase"

    ► ATP movement out is favored because the cytosol is "+" relative to


    the "-" mitochondrial matrix

    ► But ATP out and ADP in is net movement of a negative charge out
    - equivalent to a H+ going in

    ► So every ATP transported out costs one H+

    ► One ATP synthesis costs about 3 H+

    ► Thus, making and exporting 1 ATP = 4H+


    21.13 What is the P/O Ratio??
    i.e., How many ATP made per electron pair
    through the chain?
    ► e- transport chain yields 10H+ pumped out per
    electron pair from NADH to oxygen

    ► 4H+ flow back into matrix per ATP to cytosol

    ► 10/4 = 2.5 for electrons entering as NADH

    ► For electrons entering as succinate (FADH2), about 6


    H+ pumped per electron pair to oxygen

    ► 6/4 = 1.5 for electrons entering as succinate


    Net Yield of ATP from Glucose
    It depends on which shuttle is used!
    ► 32 ATP per glucose if malate-asp
    shuttle used

    ► In bacteria - no mitochondria - no
    extra H+ used to export ATP to cytosol,
    so:
    ► 10/3 = ~3ATP/NADH

    ► 6/3 = ~ 2ATP/FADH2

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