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CHAPTER 14: Energy Generation in Mitochondria

Electron Transport and Oxidative Phosphorylation

  • Key components involved in the process include:
    • NADH
    • Dehydrogenases
    • Cytochrome Complexes
    • ATP Synthase
  • Key locations:
    • Inner Mitochondrial Membrane
    • Intermembrane Space
Fundamental Processes
  • Electrons from high energy carriers (NADH and FADH2) flow through a series of membrane-bound carriers to a final electron acceptor, generating ATP.
  • Cellular respiration consists of two main processes:
    1. Electron Transport Chain (ETC)
    • Transfers energy from high energy electron carriers.
    • Creates a proton gradient across the inner mitochondrial membrane.
    1. ATP Synthase
    • Uses the proton gradient to drive ATP synthesis.

Complete Oxidation of Glucose

  • Theoretical energy yields from glucose oxidation:
    • Glycolysis:
    • ATP: 2
    • NADH: 2
    • FADH2: 0
    • CO2: 0
    • Pyruvate Dehydrogenase (PDH):
    • ATP: 0
    • NADH: 2
    • FADH2: 0
    • CO2: 2
    • Krebs Cycle:
    • ATP: 2
    • NADH: 6
    • FADH2: 2
    • CO2: 4
    • Total yield:
    • ATP: 4
    • NADH: 10
    • FADH2: 2
    • Gross CO2: 6

Structure of Mitochondria

  • Mitochondria consist of:
    • Inner Membrane
    • Impermeable, folded into cristae.
    • Outer Membrane
    • Permeable, contains porins.
    • Intermembrane Space
    • Matrix
    • Contains mitochondrial DNA and ribosomes.

Mitochondrial Pathways

  • Specific locations of various pathways:
    • Matrix:
    • Pyruvate Dehydrogenase, Krebs Cycle, Fatty acid catabolism.
    • Inner Membrane:
    • Electron Transport Chain, ATP Synthase (75% protein by weight).
  • Proteins are embedded within the membrane, allowing cellular respiration to be efficient.

Oxidative Phosphorylation

  • Consists of:
    1. Electron Transport Chain (ETC)
    2. ATP Synthase
  • Functionality: Both parts are functionally linked.
  • Electrons are donated from NADH and FADH2 to the ETC.
  • As electrons flow through the ETC, protons are displaced from the matrix to the intermembrane space, creating a proton gradient (a form of potential energy).

Types of Electron Carriers in ETC

  • Five types of electron carriers in the ETC complexes:
    1. Flavoproteins: Contain FAD or FMN.
    2. Iron-sulfur proteins: Contain iron-sulfur centers.
    3. Cytochromes: Proteins with heme groups containing iron.
    4. Cobalt-containing cytochromes: Cytochromes with copper.
    5. Coenzyme Q (Ubiquinone): Non-protein component, very lipid soluble.
  • Typical carrier reactions:
    • Complex I (NADH dehydrogenase): Oxidizes NADH, transferring electrons and pumping 4H+ to intermembrane space.
    • Complex II (Succinate dehydrogenase): Oxidizes FADH2.
    • Coenzyme Q: Transfers electrons from complexes I and II to Complex III.
    • Complex III: Transfers electrons to cytochrome c with a proton gradient.
    • Complex IV (Cytochrome c oxidase): Reduces O2 to H2O, pumping additional protons.

Function of the Electron Transport Chain

  • Generating a proton gradient and regenerating FAD and NAD+.
  • Process is highly exergonic:
    • ext{NADH + H}^+ + rac{1}{2} ext{O}2 ightarrow ext{NAD}^+ + ext{H}2 ext{O}, ext{ } ext{ΔG}°' = -52.4 ext{ kcal/mol}
    • ext{FADH}2 + rac{3}{2} ext{O}2
      ightarrow ext{FAD} + ext{H}_2 ext{O}, ext{ } ext{ΔG}°' = -45.9 ext{ kcal/mol}

Creation of the Electrochemical Gradient

  • As electrons pass through the ETC, protons are concentrated in the intermembrane space, decreasing concentration and changing pH in the matrix, creating a higher negative membrane potential.
  • This electrochemical gradient is essential for ATP synthesis.

ATP Synthase Structure and Function

  • ATP Synthase consists of:
    • Fo subunit: A transmembrane proton carrier that rotates.
    • F1 subunit: ATPase, where ATP is generated from ADP + Pi.
  • Protons flow back from intermembrane space into matrix, driving rotor activity that forces ATP synthesis through conformational changes in F1 unit.
  • ATP synthesis mechanism:
    • Proton flow induces conformational changes in the F1 subunits, facilitating bond formation between ADP and Pi.

Theoretical vs. Actual Yield of ATP from Glucose

  • Theoretical yield of ATP:
    • From 1 mole of glucose:
    • 38 moles of ATP (for bacteria), 36 moles for eukaryotes, due to mitochondrial transport costs and inefficiencies.
  • Actual yield is approximately 29 ATP per glucose for eukaryotes due to the