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Questions and Answers

In liver mitochondria incubated with a limited amount of malate, followed by the addition of cyanide, which component of the electron transport chain (ETC) will be in an oxidized state?

  • Complex II
  • Complex III
  • Complex I (correct)
  • Cytochrome c
  • CoQ

    • Isolated liver mitochondria are treated with malate, potassium, and valinomycin (which permits K+ transport across the inner mitochondrial membrane). How will this affect the proton motive force generated by malate oxidation?

  • The proton motive force will be increased.
  • There will be no change in the proton motive force.
  • The proton motive force will be decreased but to a value greater than zero. (correct)
  • The proton motive force will be reduced to a value of zero.
  • The proton motive force will be decreased to a value less than zero.

    • Dinitrophenol (DNP) is an uncoupler of oxidative phosphorylation. How does it achieve this effect?

  • Allowing for proton exchange across the inner mitochondrial membrane (correct)
  • Activating CoQ
  • Enhancing oxygen transport across the inner mitochondrial membrane
  • Activating the H+-ATPase
  • Blocking proton transport across the inner mitochondrial membrane

    • A patient with iron-deficiency anemia experiences fatigue. What is the primary reason for this fatigue related to the electron transport chain (ETC)?

    <p>Her decrease in Fe–S centers is impairing the transfer of electrons in the ETC. (A)</p> Signup and view all the answers

    In the experiment with isolated liver mitochondria and malate, what would be the immediate effect of adding an inhibitor of complex III of the ETC?

    <p>Increased reduction of complex I (B)</p> Signup and view all the answers

    Which of the following best describes the role of oxygen in the electron transport chain?

    <p>It is the final electron acceptor (E)</p> Signup and view all the answers

    Why does dinitrophenol (DNP) cause weight loss, based on its mechanism of action as an uncoupler?

    <p>It stimulates the catabolic pathway of adipose tissues, and increases heat production. (B)</p> Signup and view all the answers

    What is the primary role of iron in the electron transport chain?

    <p>To maintain the proton gradient necessary for ATP production (B)</p> Signup and view all the answers

    In a patient with an OXPHOS (oxidative phosphorylation) disease, which of the following would be expected?

    <p>An elevated NADH:NAD+ ratio within the mitochondria (D)</p> Signup and view all the answers

    Lead interferes with heme synthesis. Reduced heme would have the least effect on which protein?

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

    How does rotenone, an inhibitor of NADH dehydrogenase, affect ATP production in heart mitochondria?

    <p>Approximately a 50% reduction in ATP production (C)</p> Signup and view all the answers

    Which of the following is a key component of oxidative phosphorylation?

    <p>An ATP synthase to synthesize ATP (A)</p> Signup and view all the answers

    After treating isolated mitochondria with a high-salt solution, why is oxygen consumption minimal upon adding pyruvate and oxygen?

    <p>Loss of Cytochrome C from the electron-transfer chain. (C)</p> Signup and view all the answers

    What is a potential side effect of a drug that activates uncoupling proteins (UCPs)?

    <p>Increase in body temperature (B)</p> Signup and view all the answers

    Which of the following is unable to protect against free radical damage?

    <p>Vitamin B6 (C)</p> Signup and view all the answers

    What reaction does superoxide dismutase (SOD) catalyze?

    <p>$2\text{O}_2^- + 2\text{H}^+ \rightarrow \text{H}_2\text{O}_2 + \text{O}_2$ (C)</p> Signup and view all the answers

    Which of the following best describes the antioxidative mechanism of vitamin E?

    <p>Vitamin E participates in the reduction of the radicals. (A)</p> Signup and view all the answers

    Which metal can promote the conversion of hydrogen peroxide into dangerous radical forms?

    <p>Iron (D)</p> Signup and view all the answers

    Why is mitochondrial DNA more susceptible to oxidative damage compared with nuclear DNA?

    <p>Mitochondrial DNA lacks histones which protect DNA. (C)</p> Signup and view all the answers

    A patient with chronic granulomatous disease primarily has a deficiency in generating which substance?

    <p>Superoxide (C)</p> Signup and view all the answers

    In ALS, a mutation can lead to an inability to detoxify which of the following?

    <p>Superoxide (D)</p> Signup and view all the answers

    In high concentrations, NO can produce RNOS which are involved in which of the following diseases?

    <p>Ischemic heart disease (B)</p> Signup and view all the answers

    Study Notes

    Mitochondrial Function and Oxidative Phosphorylation

    • Electron Transport Chain (ETC) Components and Oxidized States:

      • In a specific experimental setup with malate and cyanide, Complex I and CoQ remain oxidized after 7 minutes according to the described setup.
      • Complex II, Complex III and Cytochrome C won't be in oxidized state after being exposed to cyanide in a 7-minute incubation with malate as the substrate in a mitochondria sample.

    • Proton Motive Force and Valinomycin:

      • Valinomycin, a drug that allows potassium ions to cross the inner mitochondrial membrane, reduces proton motive force (PMF).
      • The PMF decreases, disrupting the electrochemical gradient across the membrane.

    • Dinitrophenol (DNP) and Oxidative Phosphorylation Uncoupling:

      • DNP uncouples oxidative phosphorylation by allowing proton exchange across the inner mitochondrial membrane.
      • This process disrupts the proton gradient needed for ATP generation, leading to less ATP synthesis.

    Anemia and Iron Deficiency

    • Iron Deficiency Anemia and Electron Transport:

      • Iron deficiency impairs electron transport chain function due to critical roles of Fe-S centers in electron transfer.

    • Iron and TCA Cycle Enzymes:

      • Iron acts as a cofactor for α-ketoglutarate dehydrogenase in the TCA cycle.
      • This reaction supports electron flow through the ETC.

    OXPHOS Diseases

    • OXPHOS Diseases and Mitochondrial Function:
      • Patients with OXPHOS diseases typically display a high NADH/NAD+ ratio in mitochondria.
      • There is a defect in the integrity of the inner mitochondrial membrane.
      • A high ATP:ADP ratio within the mitochondria isn't typical in OXPHOS diseases.

    Lead Poisoning and Heme Synthesis

    • Lead Poisoning and Heme Synthesis:
      • Lead exposure disrupts heme synthesis.
      • This particularly affects proteins or complexes that depend on heme, such as hemoglobin, and myoglobin but not Complex I, III or IV.

    Rotenone and ATP Production

    • Rotenone Inhibition and ATP Production:
      • Rotenone inhibits NADH dehydrogenase, drastically decreasing ATP production in heart mitochondria.
      • The inhibition impacts the electron flow causing substantial losses in ATP production.

    Oxidative Phosphorylation

    • Key Components of Oxidative Phosphorylation:

      • Oxidative phosphorylation relies on using NADH and FADH2 to accept electrons when they are oxidized.
      • It necessitates the presence of ATP synthase for ATP synthesis and a source of electrons (usually oxygen).

    • Mitochondrial Membrane Disruption:

      • Disrupting non-covalent interactions at the membrane surface through high-salt solutions minimizes oxygen consumption due to loss of ETC components.
      • This loss can affect various components of the ETC.

    Uncoupling Protein (UCP) and Weight Loss

    • Uncoupling Proteins and Weight Loss Drugs:
      • Activation of UCPs could increase body temperature as a side effect of weight-loss drugs.
      • This might lead to decreased oxidation of acetyl CoA and decreased glycolysis.

    Free Radical Damage and Antioxidants

    • Free Radical Damage and Antioxidants:

      • β-carotene, glutathione peroxidase, superoxide dismutase (SOD), vitamin C, and vitamin E are antioxidants.

    • Superoxide Dismutase (SOD) Reaction:

      • SOD catalyzes the conversion of superoxide radicals to hydrogen peroxide and oxygen.
      • The reaction involves the utilization of superoxide and hydrogen ions for this process.

    • Vitamin E Mechanism:

      • Vitamin E functions as an antioxidant by participating in the reduction of free radicals.

    • Hydrogen Peroxide Conversion:

      • Iron catalyzes the conversion of hydrogen peroxide into harmful radicals.

    • Mitochondrial DNA and Oxidative Damage:

      • Mitochondrial DNA has a higher susceptibility to oxidative damage than nuclear DNA due to the permeability of the mitochondrial membrane to ROS and the lack of histones.

    Chronic Granulomatous Disease (CGD)

    • Chronic Granulomatous Disease and Immune System Defects:
      • CGD is connected to an inability to generate hypochlorous acid (HOCl) — a vital component of the immune system's response to pathogens.

    Amyotrophic Lateral Sclerosis (ALS)

    • ALS and Oxidative Stress:
      • A genetic predisposition to ALS can involve an inability to detoxify hydrogen peroxide.

    Nitric Oxide (NO) and Diseases

    • Nitric Oxide (NO) and High Concentrations:
      • High concentrations of nitric oxide (NO) can lead to the formation of reactive nitrogen species (RNS) associated with various diseases.

    Xenobiotics and Free Radical Injury

    • Xenobiotics and Free Radical Formation:
      • Exposure to xenobiotics, such as alcohol or medications, can elevate free radical injury via the induction of cytochrome P450-containing enzymes.

    Antioxidant Foods

    • Foods High in Antioxidants:
      • Citrus fruits and green leafy vegetables contain high levels of antioxidants.

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    Description

    Test your understanding of mitochondrial function, electron transport chain components, and the impact of various agents like DNP and valinomycin on oxidative phosphorylation. This quiz will cover the key processes involved in ATP generation and the mechanisms that disrupt it.

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