Mitochondria: Energy Conversion

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Objectives

• To know about the structural and biochemical
  organizations of a mitochondrion
• To understand the electrochemical reactions
  through which the chemical energy in food can be
  converted to chemical energy in ATP
• To realize how the structural organizations of
  mitochondria have allowed the above
  electrochemical reactions to be carried out
  effectively

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Energy Conversion (1) Mitochondria

• Cellular respiration
• Flow of electrons from reduced coenzymes to an
  electron acceptor generation of ATP
• NADH and FADH2 from glycolysis, TCA cycle,
  b-oxidations, etc.
• Ultimate electron acceptor is oxygen reduced
  form as water (aerobic respiration) takes place
  with mitochondria in eukaryotic cells

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The Energy Powerhouse

• Discrete sausage-shaped structures the second
  largest organelle in most animal cells
• A double-membrane organelle outer membrane
  separated from inner membrane by intermembrane
  space
• Outer membrane
• Not a significant permeability barrier for ions
  and small molecules transmembrane proteins
  (porins)

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• Intermembrane space
• Continuous with the cytosol
• Inner membrane
• A permeability barrier to most solutes
• Locale of the protein complexes of electron
  transport and ATP synthesis
• Distinctive foldings (cristae) increase surface
  area to accommodate more the protein complexes

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• Matrix
• Semi-fluid enclosed by inner membrane
• Enzymes for mitochondrial functions
• A circular DNA molecule coding for its own
  rRNAs, tRNAs, and a number of polypeptide
  subunits of inner-membrane proteins (genetic
  competence)

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Electron Transport System (ETS)

• Transfer of electrons from NADH and FADH2 is
  highly exergonic
• Multistep process a series of reversibly
  oxidizable electron carriers total free energy
  difference is released in increments to prevent
  excessive amount being released as heat (energy
  conservation for ATP)
• 4 different kinds of carriers

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• Flavoproteins
• Membrane-bound proteins using either flavin
  adenine dinucleotide (FAD) or flavin
  mononucleotide (FMN) as prosthetic group
• Transfer both electrons and protons

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• Iron-Sulfur Proteins
• Proteins containing iron-sulfur (Fe/S) centers
  iron and sulfur atoms complexed with cysteine
  groups of the protein
• Alternates between the Fe3(ferric) and
  Fe2(ferrous)
• Do not pick up and release protons
• Cytochromes (Cyt)
• Contain iron part of a porphyrin prosthetic
  group (heme)

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• One-electron carriers transfer electrons only
• Cyt b, c1, a and a3 are integral membrane
  proteins
• Cyt c is relatively hydrophilic loosely
  associated with inner face of membrane not a
  part of the complexes mobile electron carrier

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• Cyt a and a3
• Copper - containing - cytochromes (bimetallic
  iron-copper (Fe/Cu) center)
• Components of cytochrome c oxidase
• Keeping an O2 molecule bound to the oxidase
  complex completely picked up the four electrons
  and four protons

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• Coenzyme Q (CoQ)
• Ubiquinone (a benzene derivative) the only
  nonprotein component
• Carries both protons and electrons
• Not part of a respiratory complex a collection
  point for electrons from FMN- and FAD-linked
  dehydrogenases
• Active transport of protons across inner
  mitochondrial membrane

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• The electron carriers function in a sequence
  determined by their relative reducing power
  (reduction potentials)
• Two interconvertible molecules or ions by the
  loss or gain of electrons (redox pair)
• With exceptions of CoQ and Cyt c, the electron
  carriers are organized into four large
  multiprotein complexes (respiratory complexes)

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• Complex I
• NADH-coenzyme Q oxidoreductase
• Transfers electrons from NADH to coenzyme Q
• Complex II
• Succinate-coenzyme Q oxidoreductase
• Transfers electrons derived from succinate
  oxidation in TCA

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• Complex III
• Coenzyme Q cytochrome c oxidoreductase
• Accepts electrons from coenzyme Q and passes them
  to cytochrome c
• Complex IV
• Cytochrome c oxidase
• A terminal oxidase capable of direct transfer of
  electrons to oxygen

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Properties of the Mitochondrial Respiratory
Complexes
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ATP Generation / Electron Transport

• ATP generation ADP Pi ?ATP
• Photophosphorylation
• Substrate level phosphorylation
• Glycolysis 1,3-bisphosphoglycerate ?
  3-phospho-glycerate phosphoenolpyruvate ?
  pyruvate
• TCA succinyl CoA ? succinate
• 4 ATP molecules/glucose 2 from glycolysis 2
  from TCA

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• Oxidative phosphorylation
• 6 different oxidations (12 pairs of electrons)
• Glycolysis glyceraldehyde-3-phosphate ?
  1,3-bisphosphoglycerate (NADH)
• Pyruvate ? acetyl CoA (NADH)
• TCA isocitrate ? ?-ketoglutarate (NADH) ?-KG ?
  succinyl CoA (NADH) succinate ? fumarate
  (FADH2) malate ? oxaloacetate (NADH)

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Chemiosmotic Model

• Electrochemical potential across a membrane the
  link between electron transport and ATP formation
  
• Exergonic transfer of electrons between and
  within respiratory complexes unidirectional
  pumping of protons across the membrane where the
  transport system is localized

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The F0F1 Complex

• A F-type ATPase both ATPase and ATP synthase
  activities
• Converts electrochemical energy (proton gradient)
  into potential chemical energy (ATP)
• F1 complex
• 3a and 3b polypeptides 3 ab complexes (catalytic
  hexagon)

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• ? subunit catalytic site for ATP
  synthesis/hydrolysis a subunit ATP/ADP-binding
  site
• Both ATP synthase and ATPase activities
• Proton translocation through F0 drives ATP
  synthesis by F1
• Stalk
• Composes of ?, ? and ? subunits
• Allows rotation of F1 complex about F0 complex

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• F0 complex
• Consists of 1a, 2b and 9-12 c subunits
• c subunits are organized in a circle proton
  channel
• As a proton translocator channel through which
  protons flow (protonation and deprotonation of
  aspartate)

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Binding Change Model

• To explain how exergonic flow of protons through
  F0 can drive endergonic phosphorylation of ADP to
  ATP
• Electrochemicaltomechanicaltochemical
  transducer
• Each of the three b subunits exists in 3
  different conformations at any point in time

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• (O)pen little affinity ADP and Pi are free to
  enter (ATP is free to leave) the catalytic site
• (L)oose higher affinity lose binding of ADP and
  Pi
• (T)ight Packing the ADP and Pi together tightly
  facilitating the condensation
• O ? L ? T

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• Flowing of protons flow through a channel in the
  a subunit of F0
• Rotation of the ring of c subunits rotation of
  the attached g subunit
• Asymmetry of the g subunit different
  interactions with the three b subunits at any
  point in time
• Each b subunit passes successively through the O,
  L, and T conformations as the g subunit rotates
  360º

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