Electron Transport Chain

  • Electron transport chain and oxidative phosphorylation
    • Overview of the electron transport chain(ETC)
      • NADH and FADH2 are produced by glycolysis, b-oxidation of fatty acids, the TCA cycle, and other oxidative reactions.(MCQ)
      • NADH and FADH2 pass electrons to the components of the ETC, which are located in the inner mitochondrial membrane.(MCQ)
        • NADH freely diffuses from the matrix to the membrane
        • whereasFADH2 is tightly bound to enzymes that produce it within the inner mitochondrial membrane.(MCQ)
      • Mitochondria are separated from the cytoplasm by two membranes.
        • The soluble interior of a mitochondrion is called the matrix.
        • The matrix is surrounded by the inner membrane, which contains vast infoldings to increase surface area, known as cristae.
      • The transfer of electrons from NADH to oxygen (O2) occurs in three stages, each of which involves a large protein complex in the inner mitochondrial membrane.
        • Some of the genes for the large protein complexes are encoded by nuclear DNA, while others are coded for by mitochondrial DNA (mtDNA).(MCQ)
        • Each complex uses the energy from electron transfer to pump protonsto the cytosolic side of the inner mitochondrial membrane.
      • An electrochemical potential or proton-motive force is generated
        • ATP is produced as the protons enter back into the matrix through the ATP synthase complex.
        • During the transfer of electrons through the ETC,some of the energy is lost as heat.
        • The electron transport chain has a large negative G0’, thus electrons flow from NADH (or FADH2) toward O2.(MCQ)
    • Components of the electron transport chain
      • The reduced cofactors, NADH and FADH2 ,transfer electrons to the ETC.
        • Flavin mononucleotide (FMN)receives electrons from NADH and transfers them through iron- sulfur (Fe-S) centers to coenzyme Q(MCQ)
        • FMN is derived from riboflavin.
      • Coenzyme Q (CoQ)
        • receiveselectrons from FMN and also through Fe-S centers from FADH2(MCQ)
        • FADH2 is not free in solution like NAD+ and NADH; it is tightly bound to enzymes.
        • CoQ can be synthesized in the body.
        • It is not derived from a vitamin.
      • Cytochromes receive electrons from the reduced form of CoQ.
        • Each cytochrome consists of a heme group associated with a protein.
        • The iron of the heme group I reduced when the cytochrome accepts an electron.
        • Fe3+ becomes Fe2+(MCQ)
        • Heme is synthesized from glycine and succinyl coenzyme A (CoA) in humans(MCQ)
      • O2 ultimately receives the electrons at the end of the electron transport chain and is reduced to water (H2O).
  • The three major stages of electron transport
    • Transfer of electrons from NADH to coenzyme Q(ComplexI)
    • NADH passes electrons via the NADH dehydrogenase complex to FMN.
      • NADH is produced by the alpha-ketoglutarate dehydrogenase, isocitrate dehydrogenase, and malate dehydrogenase reactions of the TCA cycle, by the PDH reaction that converts pyruvate to acetyl CoA, by beta-oxidation of fatty acids, and by other oxidationreactions.(MCQ)
      • NADH produced in the mitochondrial matrix diffuses to the inner mitochondrial membrane where it passes electrons to FMN, which is tightly bound to a protein..(MCQ)
      • FMN passes the electrons through a series of Fe-S protein complexes to CoQ, whichaccepts electrons one at a time, forming first the semiquinone and then ubiquinol.
      • The energy produced by these electron transfers is used to pump protons to the cytosolic side of the inner mitochondrial membrane.
    • Transfer of electrons from CoQtocyto chrome C
      • CoQ passes electrons through Fe-S centers to cyto chromes b and c1 (complex III), which transfer the electrons to cytochrome c(MCQ)
        • The protein complex involved in these transfers is called cytochrome c reductase.
        • These cytochromes each contain heme as a prosthetic group but have different apoproteins.
        • In the ferric (Fe3+) state, the heme iron can accept one electron and be reduced to the ferrous (Fe2+) state.
        • Because the cytochromes can only carry one electron at a time, CoQ acts as an adapter between the two electron transfers in complex I, and the one electron transfer in com-plex III.(MCQ)
      • The energy produced by the transfer of electrons from CoQ to cytochrome c is used to pump protons across the inner mitochondrial membrane
        • Proton flow back into the mitochondrial matrix, via the ATP synthase, will drive ATP synthesis.(MCQ)
      • Electrons from FADH2 (complex II), produced by reactions such as the oxidation of succinate to fumarate by succinate dehydrogenase, enter the electron transport chain at the CoQ level(MCQ)
    • Transfer of electrons from cyto chromec to oxygen
      • Cytochrome c transfers electrons to the cytochrome aa3 complex(complex IV), whichtransfers the electrons to molecular O2, reducing it to H2O.
        • Cytochrome c oxidase catalyzes this transfer of electrons(MCQ)
        • Cytochromes a and a3 each contain a heme and two different proteins that each contain copper.(MCQ)
        • Two electrons are required to reduce 1 atom of O2; therefore, for each mole of NADH that is oxidized, 1/2 mole of O2 is converted to H2O.(MCQ)
      • The energy produced by the transfer of electrons from cytochrome c to O2 is used to pump protons across the inner mitochondrial membrane.
  • ATP production
    • As elements of the ETC pass electrons from complex I to IV, an electrochemical potential or proton-motive force is generated.
    • The electrochemical potential consists of both a membrane potentialand a pHgradient.
    • The cytosolic side of the membrane is more acidic (i.e., has a higher [H+]) than thematrix.
    • The protons can reenter the matrix only through the ATP synthase complex(complex V, theF0–F1/ATPase), causing ATP to be generated.
      • Theinnermitochondrialmembraneisimpermeabletoprotons.
      • The (F0) component forms a channelin the inner mitochondrial membrane, throughwhich protons can flow.
      • The (F1) is the ATP-synthesizing head, projecting into the mitochondrial matrix that is connected to the F0 portion via a stalk.
    • Total ATP production
      • For every mole of NADH that is oxidized, 1/2 mole of O2 is reduced to H2O, and about 2.5 moles of ATP are produced. (MCQ)
        • Each mole of NADH oxidized leads to 10 moles of protons being extruded from the matrix.
        • Because it requires four moles of protons entering the ATP synthase to generate one mole of ATP, 2.5 moles of ATP can be generated per 10 moles of protons extruded.
      • For every mole of FADH2 that is oxidized, about 1.5 moles of ATP are generated because the electrons from FADH2 enter the chain via CoQ, bypassing the NADH dehydrogenase step(MCQ)
        • For each mole of FADH2 oxidized, six moles of protons are extruded across the inner mitochondrial membrane.
    • The ATP-ADP antiport.
      • ATP produced within mitochondria is transferred to the cytosol in exchange for ADP by a transport protein in the inner mitochondrial membrane known as the ATP-ADP antiporter (adenine nucleotide translocase [ANT])


Inhibitors of the electron transport chain (A Very High yield MCQ Topic )


  • Applied aspects
    • Leber’shereditary optic neuropathy (LHON)(MCQ)
      • mitochondrial DNA (mtDNA) disorder
      • have point mutations in the gene for cytochrome reductase
      • Patients are typically males in their20s to 30s who develop loss of central vision.
    • Kearns-Sayre syndrome(MCQ)
      • mtDNA defect known
      • havemutations in complex II of the ETC.
      • These patients manifest with short stature, complete external ophthalmoplegia, pigmentary retinopathy, ataxia, and cardiac conduction defects
    • Leigh disease(MCQ)
      • An mt DNA disorder
      • mutations in cytochrome oxidase.
      • present with lactic acidemia,developmental delay, seizure, extraocular palsies, and hypotonia.
      • The disorder is usually fatal by the age of 2 years

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