Harper's Biochemistry Chapter 13 - The Respiratory Chain & Oxidative Phosphorylation
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What is required for the net uptake of malate by the dicarboxylate transporter?

  • Inorganic phosphate (correct)
  • Citrate
  • Hydroxide ions
  • ADP

    • Which anions require specific transporter systems to facilitate their passage across the membrane?

  • Sulfate and phosphate ions
  • Chloride and potassium ions
  • Single carboxylate ions
  • Dicarboxylate and tricarboxylate anions (correct)

    • What is the exchange required for the net uptake of citrate, isocitrate, or cis-aconitate by the tricarboxylate transporter?

  • Malate (correct)
  • Glutamate
  • Citrate itself
  • ADP

    • Which compound does NOT require a transporter to cross the mitochondrial membrane as discussed?

    <p>Inorganic phosphate</p> Signup and view all the answers

    Which transporter allows for the exchange of ATP and ADP within the mitochondrion?

    <p>Adenine nucleotide transporter</p> Signup and view all the answers

    What does the transport of α-ketoglutarate require for its exchange?

    <p>Exchange with malate</p> Signup and view all the answers

    What type of substances do the transporter systems also facilitate besides dicarboxylate and tricarboxylate anions?

    <p>Neutral amino acids</p> Signup and view all the answers

    What is a consequence of the transport of dicarboxylate anions in relation to hydroxide ions?

    <p>They are exchanged for inorganic phosphate.</p> Signup and view all the answers

    What is the role of the respiratory chain complexes in the inner mitochondrial membrane?

    <p>To transport protons outside the membrane using energy from redox reactions</p> Signup and view all the answers

    Which process is critically linked to the synthesis of ATP?

    <p>Generation of a proton gradient through the electron transport chain</p> Signup and view all the answers

    What is the function of ATP synthase in the mitochondria?

    <p>To use proton motive force to convert ADP and Pi into ATP</p> Signup and view all the answers

    In the context of energy production, what is the final product of the reaction involving oxygen in the respiratory chain?

    <p>Water</p> Signup and view all the answers

    What is the primary purpose of the electrochemical potential created by the respiratory chain?

    <p>To enable the synthesis of ATP through a rotary mechanism</p> Signup and view all the answers

    What is the primary role of reducing equivalents generated from the oxidation of foodstuffs?

    <p>To be collected by the respiratory chain for ATP generation</p> Signup and view all the answers

    Which complex in the respiratory chain is associated with the reduction of succinate?

    <p>Complex II</p> Signup and view all the answers

    What molecule is oxidized in Complex I of the respiratory chain?

    <p>NADH</p> Signup and view all the answers

    What is the end product of electron flow through Complex IV?

    <p>Water</p> Signup and view all the answers

    Which component acts as an intermediary electron carrier between Complex II and Complex III?

    <p>Q (ubiquinone)</p> Signup and view all the answers

    Which of the following is NOT a component of the respiratory chain as depicted?

    <p>Fumarate</p> Signup and view all the answers

    What is the primary function of the respiratory chain in cell metabolism?

    <p>To oxidize metabolites and generate ATP</p> Signup and view all the answers

    Which complex directly reduces and transfers electrons to cytochrome c?

    <p>Complex III</p> Signup and view all the answers

    How do reducing equivalents contribute to ATP generation?

    <p>By transferring electrons to generate a proton gradient</p> Signup and view all the answers

    Which of the following statements about mitochondria's respiratory chain is true?

    <p>Multiple complexes are involved in electron transfer</p> Signup and view all the answers

    What effect does increasing respiration have on the cell?

    <p>It approaches states 3 or 5.</p> Signup and view all the answers

    Which compound acts as a competitive inhibitor of Complex II?

    <p>Malonate</p> Signup and view all the answers

    How does Atractyloside disrupt oxidative phosphorylation?

    <p>By inhibiting the ADP/ATP transporter.</p> Signup and view all the answers

    What is the primary function of ATP synthase in the respiratory chain?

    <p>To facilitate proton flow and ATP production.</p> Signup and view all the answers

    What is the role of uncouplers like 2,4-dinitrophenol in the respiratory chain?

    <p>They disconnect oxidation from phosphorylation.</p> Signup and view all the answers

    What consequence does the antibiotic oligomycin have on cellular respiration?

    <p>It blocks proton flow through ATP synthase.</p> Signup and view all the answers

    What happens when the concentration of ADP or inorganic phosphate is low?

    <p>The capacity of the respiratory chain becomes limited.</p> Signup and view all the answers

    Which poison is known to inhibit Complex IV, affecting respiration?

    <p>Cyanide</p> Signup and view all the answers

    What is a primary outcome of uncoupling oxidative processes?

    <p>Heat generation due to uncontrolled respiration.</p> Signup and view all the answers

    Which component is primarily affected when the concentration of PO2 decreases below the Km for heme a3?

    <p>Complex IV function.</p> Signup and view all the answers

    What is the primary role of ionophores in the context of mitochondrial membranes?

    <p>To facilitate the transport of specific cations through the membrane</p> Signup and view all the answers

    Which molecule cannot penetrate the mitochondrial membrane but is continuously produced in the cytosol?

    <p>NADH</p> Signup and view all the answers

    What mechanism allows for calcium release from mitochondria?

    <p>Exchange with sodium via antiport</p> Signup and view all the answers

    What is the role of the glycerophosphate shuttle?

    <p>To transport reducing equivalents from the cytosol to the mitochondrion</p> Signup and view all the answers

    Which of the following best describes the oxidation of extramitochondrial NADH?

    <p>It is mediated by substrate shuttles that transfer it into the mitochondria.</p> Signup and view all the answers

    What is the effect of the proton gradient on calcium uptake by mitochondria?

    <p>It is driven by the gradient through calcium uniport.</p> Signup and view all the answers

    What is the primary function of dinitrophenol as mentioned in the context?

    <p>To act as a proton ionophore that uncouples oxidative phosphorylation</p> Signup and view all the answers

    Which enzyme is involved in producing NADH in the glycolysis sequence?

    <p>Glyceraldehyde-3-phosphate dehydrogenase</p> Signup and view all the answers

    In what manner does NADH typically behave under aerobic conditions?

    <p>It is oxidized by the respiratory chain in mitochondria.</p> Signup and view all the answers

    What drives the exchange of Na+ for H+ in mitochondria?

    <p>The established proton gradient</p> Signup and view all the answers

    What is the relationship between inorganic phosphate and dicarboxylate anions in transport mechanisms?

    <p>Inorganic phosphate is exchanged for malate during dicarboxylate transport.</p> Signup and view all the answers

    Which of the following correctly describes the exchange process during the transport of citrate?

    <p>Malate is exchanged in the transport of citrate, isocitrate, or cis-aconitate.</p> Signup and view all the answers

    What characterizes the adenine nucleotide transporter in the mitochondrial membrane?

    <p>It facilitates the exchange of ADP and ATP.</p> Signup and view all the answers

    Which of the following molecules does NOT require a specific transporter system to cross the mitochondrial membrane?

    <p>Inorganic phosphate</p> Signup and view all the answers

    What effect does N-Ethylmaleimide have on transporter systems in the inner mitochondrial membrane?

    <p>It specifically inhibits dicarboxylate and tricarboxylate transport systems.</p> Signup and view all the answers

    Which transporter system also plays a role in the transport of glutamate/aspartate?

    <p>Dicarboxylate transporter</p> Signup and view all the answers

    What is a key functional aspect of the transport of α-ketoglutarate in the inner mitochondrial membrane?

    <p>It requires malate for exchange during translocation.</p> Signup and view all the answers

    During the transport processes discussed, which of the following statements is true regarding hydroxide ions?

    <p>They are exchanged for inorganic phosphate in the transport process.</p> Signup and view all the answers

    Which complex directly participates in the transport of electrons from NADH within the respiratory chain?

    <p>Complex I</p> Signup and view all the answers

    What is the role of Coenzyme Q in the respiratory chain?

    <p>It accepts and donates electrons during the Q cycle.</p> Signup and view all the answers

    What role does cytochrome c play in the respiratory chain?

    <p>Acts as an electron carrier</p> Signup and view all the answers

    Which component accepts electrons from FADH2 during its transfer through the respiratory chain?

    <p>Ubiquinone (Q)</p> Signup and view all the answers

    Which component of Complex IV is essential for minimizing harmful intermediates when O2 is reduced?

    <p>Heme a3</p> Signup and view all the answers

    Which of the following correctly describes the electron flow in Complex III?

    <p>It utilizes the Q cycle to manage electron distribution.</p> Signup and view all the answers

    During the Q cycle, how many protons are released into the intermembrane space during the oxidation of one molecule of QH2?

    <p>Two protons</p> Signup and view all the answers

    What structural feature of ATP synthase allows it to function as a rotary motor?

    <p>F0 subunit forming a proton channel</p> Signup and view all the answers

    Which molecule is primarily produced as a result of the electron transport chain's final reaction?

    <p>Water</p> Signup and view all the answers

    What is the primary function of quinone (Q) in the respiratory chain?

    <p>Acts as a mobile electron carrier between complexes</p> Signup and view all the answers

    What happens to the semiquinone form during the Q cycle?

    <p>It is reduced to form QH2 upon accepting another electron.</p> Signup and view all the answers

    Which complex in the electron transport chain is linked to the reduction of oxygen?

    <p>Complex IV</p> Signup and view all the answers

    Which of the following statements about the role of ATP synthase is false?

    <p>It operates independently of the respiratory chain.</p> Signup and view all the answers

    What is primarily minimized by the tightly bound O2 at Complex IV?

    <p>Formation of superoxide anions</p> Signup and view all the answers

    How does the proton gradient influence ATP synthesis in mitochondria?

    <p>It creates a potential energy difference that drives ATP synthesis.</p> Signup and view all the answers

    What initiates the flow of electrons through the respiratory chain?

    <p>Oxidation of NADH and FADH2</p> Signup and view all the answers

    Which of the following best describes the composition of the F1 subunit of ATP synthase?

    <p>It contains several protein subunits arranged around an axis.</p> Signup and view all the answers

    Which component is involved in transferring electrons between Complex I and Complex III?

    <p>Ubiquinone (Q)</p> Signup and view all the answers

    The donation of electrons from QH2 to cytochrome c occurs through which components of the respiratory chain?

    <p>Rieske Fe-S and cytochrome c1</p> Signup and view all the answers

    What is the primary role of proton-translocating transhydrogenase in the mitochondrial membrane?

    <p>It facilitates the transfer of NADH to NADP.</p> Signup and view all the answers

    Which statement accurately reflects the efficiency of ATP production linked to the mitochondrial enzyme mentioned?

    <p>1.5 mol of ATP are formed per atom of oxygen consumed.</p> Signup and view all the answers

    What key function does the malate shuttle system serve in cellular metabolism?

    <p>It transfers reducing equivalents from the cytosol into the mitochondrion.</p> Signup and view all the answers

    How does the impermeability of the mitochondrial membrane impact the transport of oxa-lacetate?

    <p>It necessitates the formation of intermediates for transport.</p> Signup and view all the answers

    Which of the following compounds is directly utilized by the mitochondrial transport systems for exchanging reducing equivalents?

    <p>Malate</p> Signup and view all the answers

    Which component is primarily responsible for synthesizing ATP in mitochondria?

    <p>ATP synthase</p> Signup and view all the answers

    What is the primary purpose of the chemiosmotic theory in cellular respiration?

    <p>To explain the proton gradient's role in ATP generation</p> Signup and view all the answers

    Which respiratory chain complex directly contributes to the reduction of oxygen in the electron transport chain?

    <p>Complex IV</p> Signup and view all the answers

    What role do uncouplers, such as 2,4-dinitrophenol, play in mitochondrial function?

    <p>Inhibit ATP synthesis</p> Signup and view all the answers

    What is a consequence of a low concentration of ADP or inorganic phosphate in mitochondrial respiration?

    <p>Inhibition of electron transport</p> Signup and view all the answers

    Which statement best describes the role of reducing equivalents generated during cellular respiration?

    <p>They donate electrons to the respiratory chain</p> Signup and view all the answers

    Which molecule is primarily affected by the antibiotic oligomycin in mitochondrial respiration?

    <p>ATP synthase</p> Signup and view all the answers

    What specific effect does the concentration of PO2 have on mitochondrial respiration?

    <p>It affects the reduction reaction in Complex IV</p> Signup and view all the answers

    In what manner does the proton gradient created in mitochondria primarily function in energy production?

    <p>It directly catalyzes ATP synthesis</p> Signup and view all the answers

    Match the following complexes of the respiratory chain with their primary function:

    <p>Complex I = NADH-Q oxidoreductase Complex II = Succinate-Q reductase Complex III = Q-cyt c oxidoreductase Complex IV = Cyt c oxidase</p> Signup and view all the answers

    Match the following molecules with their roles in the respiratory chain:

    <p>NADH = Electron donor Fumarate = Intermediate in the citric acid cycle Q (Coenzyme Q) = Mobile electron carrier Cyt c = Intermediary electron carrier</p> Signup and view all the answers

    Match the following reducing equivalents with their hydrogen contribution:

    <p>NADH + H+ = 2H from glucose oxidation Fumarate = 2H during molecular transformation Q = H participated in electron transport Cyt c = H transfer to Complex IV</p> Signup and view all the answers

    Match the following electron flow components with their associated reactions:

    <p>Complex I = Oxidizes NADH Complex II = Oxidizes succinate Complex III = Transfers electrons to cyt c Complex IV = Reduces oxygen to water</p> Signup and view all the answers

    Match the following outcomes with their corresponding inputs in the respiratory chain:

    <p>NADH + H+ = Generates reducing equivalents Succinate = Substrate for Complex II Q = Links Complexes II and III Cyt c = Transports electrons to Complex IV</p> Signup and view all the answers

    Match the following components of the respiratory chain with their respective functions:

    <p>Complex I = Transfers electrons from NADH to coenzyme Q Complex II = Transfers electrons from FADH2 to coenzyme Q Complex III = Transfers electrons from coenzyme Q to cytochrome c Complex IV = Reduces oxygen to water</p> Signup and view all the answers

    Match the following substances with their roles in oxidative phosphorylation:

    <p>Coenzyme Q = Electron carrier between complexes Cytochrome c = Accepts electrons from Complex III ATP synthase = Generates ATP from ADP and Pi Proton gradient = Drives ATP synthesis</p> Signup and view all the answers

    Match the following protein types with their characteristics in the respiratory chain:

    <p>Flavoproteins = Involved in electron transfer from NADH Iron-sulfur proteins = Participate in electron transfer Coenzyme Q = Lipid-soluble electron carrier Cytochromes = Contain heme groups for electron transport</p> Signup and view all the answers

    Match the following terms with their descriptions related to the respiratory chain:

    <p>Oxidative phosphorylation = Process of ATP generation linked to electron transport Proton motive force = Energy stored due to the proton gradient Electron transport chain = Series of complexes transferring electrons Reduction = Gaining electrons during the reactions</p> Signup and view all the answers

    Match the following poisons with their site of action in the respiratory chain:

    <p>Cyanide = Inhibits Complex IV Rotenone = Inhibits Complex I Antimycin A = Inhibits Complex III Oligomycin = Inhibits ATP synthase</p> Signup and view all the answers

    Study Notes

    Transport Systems of Dicarboxylates and Tricarboxylates Across the Inner Mitochondrial Membrane

    • Dicarboxylate and tricarboxylate anions (e.g., malate, citrate) require specific transport systems to cross the inner mitochondrial membrane.
    • The transport of di- and tricarboxylate anions is linked to the transport of inorganic phosphate, which readily passes as H2PO4- in exchange for OH-.
    • The dicarboxylate transporter requires exchange with inorganic phosphate for the net uptake of malate.
    • The tricarboxylate transporter uses malate for the net uptake of citrate.
    • Malate is also required for alpha-ketoglutarate transport.
    • The adenine nucleotide transporter facilitates the exchange of ATP and ADP.
    • The adenine nucleotide transporter is crucial for ATP exit from the mitochondria and ADP return for further ATP production.

    The Respiratory Chain

    • The respiratory chain is responsible for oxidizing reducing equivalents generated from the breakdown of major foodstuffs.
    • The redox carriers of the respiratory chain are organized into four complexes within the inner mitochondrial membrane.
    • Complexes I, III, and IV pump protons across the inner membrane to create an electrochemical potential.
    • This potential energy is used by ATP synthase to produce ATP from ADP and inorganic phosphate.

    The Glycerophosphate Shuttle

    • NADH cannot cross the mitochondrial membrane.
    • The glycerophosphate shuttle is used to transfer reducing equivalents from NADH in the cytosol to the mitochondria.
    • Glycerol-3-phosphate dehydrogenase in the cytosol oxidizes NADH to transfer reducing equivalents to dihydroxyacetone phosphate.
    • Dihydroxyacetone phosphate crosses the membrane and is reduced to glycerol-3-phosphate by mitochondrial glycerol-3-phosphate dehydrogenase.
    • This process generates FADH2, which delivers electrons to the respiratory chain.

    Inhibitors and Uncouplers of Oxidative Phosphorylation

    • Malonate is a competitive inhibitor of Complex II in the respiratory chain.
    • Atractyloside inhibits the adenine nucleotide transporter, preventing ADP entry into and ATP exit from the mitochondria.
    • Oligomycin inhibits the flow of protons through ATP synthase, completely blocking oxidative phosphorylation.
    • Uncouplers such as 2,4-dinitrophenol dissociate oxidation from phosphorylation, causing uncontrolled respiration.

    Ionophores

    • Ionophores are lipophilic molecules that facilitate the transport of specific cations across membranes.
    • Valinomycin acts as a K+ ionophore.
    • Uncouplers are proton ionophores.

    Other Intramitochondrial Transport Systems

    • Glutamate/aspartate, glutamine, ornithine, neutral amino acids, and carnitine are transported across the mitochondrial membrane by specific transporters.

    Regulation of the Respiratory Chain

    • The concentration of inorganic phosphate impacts the rate of respiration.
    • The ADP/ATP transporter can become rate-limiting at high respiratory rates.

    Summary

    The respiratory chain is a series of protein complexes located in the inner mitochondrial membrane that oxidize reducing equivalents, generating energy in the form of ATP. This process is carefully regulated by factors such as the concentration of inorganic phosphate and the availability of ADP. The respiratory chain is essential for cellular energy production and is the primary target of a number of toxins and drugs that inhibit or uncouple its function.

    Transport of Di- and Tricarboxylates

    • Dicarboxylate and tricarboxylate anions, such as malate and citrate, require specific transport systems to cross the mitochondrial membrane.
    • Di- and tricarboxylate transport is coupled to inorganic phosphate (H2PO4-) transport in exchange for OH-.
    • Malate uptake by the dicarboxylate transporter requires inorganic phosphate to be transported in the opposite direction.
    • Citrate, isocitrate, or cis-aconitate uptake by the tricarboxylate transporter requires malate in exchange.
    • α-Ketoglutarate transport is also coupled to malate exchange.

    Adenine Nucleotide Transporter

    • Allows for the exchange of ATP and ADP, but not AMP.
    • Crucial for ATP to exit mitochondria for extramitochondrial utilization and for ADP to return for ATP production within the mitochondrion.

    Respiratory Chain Complexes

    • Complexes I, II, III, and IV are involved in the electron transport chain.
    • Each complex pumps protons across the membrane.
    • Complex IV binds oxygen tightly to prevent the release of harmful intermediates like superoxide anions or peroxide.

    ATP Synthase

    • ATP synthase is a membrane-bound enzyme that uses the proton motive force to produce ATP from ADP and inorganic phosphate.
    • Contains two main components: F1 and F0.
    • F1 is a ball-like structure that projects into the mitochondrial matrix.
    • F0 spans the membrane and forms a proton channel.

    Proton-Translocating Transhydrogenase

    • Couples proton movement down the electrochemical gradient with the transfer of H from NADH to NADP, forming NADPH.
    • Located in the inner mitochondrial membrane.

    Malate Shuttle

    • Used to transfer reducing equivalents from the cytosol to the mitochondrion.
    • Oxaloacetate is converted to malate, which crosses the inner membrane in exchange for α-ketoglutarate.
    • Malate is then converted back to oxaloacetate, releasing NADH within the matrix.

    Creatine Kinase

    • Transfers a phosphate group from ATP to creatine, forming phosphocreatine.
    • Serves as a phosphate reservoir within the cell.
    • Provides a rapid source of energy for muscle contraction.

    Respiratory Chain and Oxidative Phosphorylation

    • The respiratory chain is the final process in the oxidation of fuel substrates (fats, carbohydrates, amino acids)
    • The chain generates energy through a series of protein complexes, collectively called the respiratory chain.
    • The respiratory chain passes electrons through a series of complexes until they are finally reacted with oxygen to form water.
    • Mitochondria have a double membrane structure with various enzymes located in different regions.
    • Energy from the oxidation of fuel substrates is almost all generated in the mitochondria via a process termed electron transport.
    • There are four protein complexes involved in the transfer of electrons through the respiratory chain.
    • **Complex I (NADH-Q oxidoreductase) ** receives electrons from NADH and transfers them to Coenzyme Q.
    • Complex II (succinate-Q reductase) receives electrons from FADH2 and transfers them to Coenzyme Q.
    • ** Complex III (Q-cyt c oxidoreductase)** receives electrons from Coenzyme Q and transfers them to cytochrome c.
    • ** Complex IV (cyt c oxidase)** receives electrons from reduced cytochrome c and oxidizes them, while reducing oxygen to form water.

    Respiratory Chain Complexes

    • Complex I: Contains flavin mononucleotide (FMN) and iron-sulfur (Fe-S) proteins, which accept electrons from NADH.
    • Complex II: Contains FAD, Fe-S proteins, and cytochromes b.
    • Complex III: Contains cytochrome b, cytochrome c1, and an Fe-S protein known as the Rieske protein.
    • Complex IV: Contains cytochromes a and a3, and also uses copper ions.

    Electron Transfer

    • Coenzyme Q (ubiquinone) is a mobile electron carrier that can accept electrons from both Complex I and Complex II.
    • Electrons are passed from reduced coenzyme Q to cytochrome c via Complex III through a process called the Q cycle.
    • The Q cycle involves the transfer of electrons from QH2 to cytochrome c, while simultaneously creating a semiquinone intermediate.

    Proton Gradient

    • As electrons flow through the respiratory chain, protons are pumped across the inner mitochondrial membrane from the matrix to the intermembrane space.
    • This creates a proton gradient, which stores energy.
    • The proton gradient is called the proton motive force.

    ATP Synthase

    • ATP synthase is a complex enzyme that utilizes the proton motive force to produce ATP from ADP and Pi.
    • It has two main parts: F1, which projects into the matrix and contains the phosphorylation mechanism, and F0, a membrane protein complex that forms a proton channel.
    • The proton flow through F0 drives the rotation of F1, which in turn catalyzes the formation of ATP.

    Respiratory Control

    • The rate of respiration is regulated by the availability of ADP, substrate, and oxygen.
    • State 1 respiration is limited by the availability of ADP and substrate.
    • State 2 respiration is limited by the availability of substrate.
    • State 3 respiration is limited by the capacity of the respiratory chain itself.
    • State 4 respiration is limited by the availability of ADP.
    • State 5 respiration is limited by the availability of oxygen.

    Poisons that Inhibit the Respiratory Chain

    • Some poisons inhibit the respiratory chain by blocking specific complexes or the electron transfer process.
    • Barbiturates such as amobarbital inhibit Complex I.
    • Antimycin A inhibits Complex III.
    • Dimercaprol inhibits Complex III.
    • Cyanide inhibits Complex IV, blocking the transfer of electrons to oxygen.
    • Carbon monoxide binds to Complex IV and prevents oxygen from being reduced.

    Uncouplers of Oxidative Phosphorylation

    • Uncouplers disrupt the coupling of electron transport and ATP synthesis.
    • They dissipate the proton gradient without generating ATP.
    • Examples of uncouplers include 2,4-dinitrophenol (DNP) and valinomycin.
    • Uncouplers increase respiration but prevent ATP synthesis.

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    Explore the mechanisms of dicarboxylate and tricarboxylate transport across the inner mitochondrial membrane. Understand how these transport systems are interrelated with phosphate transport and the function of the adenine nucleotide transporter in ATP and ADP exchange.

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