Biochemistry: Pyruvate Oxidation and TCA Cycle
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What is the function of the pyruvate dehydrogenase complex (PDHc) in cellular metabolism?

  • To synthesize GTP from acetic acid
  • To convert acetyl-CoA to pyruvate
  • To generate NAD+ from NADH
  • To oxidize pyruvate to acetyl-CoA and CO2 (correct)
  • Which components are vital for the regulation of the TCA cycle?

  • NADH levels only
  • ATP levels and enzyme concentration
  • Acetyl-CoA concentration exclusively
  • Substrate availability and allosteric effectors (correct)
  • How does the respiratory chain utilize reducing equivalents during cellular respiration?

  • By storing them as fat
  • Through direct conversion into ATP without a proton gradient
  • By converting them back into glucose
  • By oxidizing NADH and FADH2 and acting as a proton pump (correct)
  • Which enzyme catalyzes a reaction in the TCA cycle that produces reducing equivalents?

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

    What role do mobile electron carriers such as coenzyme Q and cytochrome c play in the respiratory chain?

    <p>They transfer electrons between the protein complexes</p> Signup and view all the answers

    What is a potential consequence of a deficiency in the pyruvate dehydrogenase complex?

    <p>Accumulation of lactic acid due to anaerobic metabolism</p> Signup and view all the answers

    Which theory explains the process of ATP synthesis in oxidative phosphorylation?

    <p>The chemiosmotic theory</p> Signup and view all the answers

    Which factor does not influence the activity of the TCA cycle enzymes?

    <p>Dietary intake of carbohydrates</p> Signup and view all the answers

    What is the primary action of inhibitors on the respiratory chain?

    <p>They inhibit the process of oxidative phosphorylation.</p> Signup and view all the answers

    Which complex does cyanide inhibit in the electron transport chain?

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

    How does the binding affinity of carbon monoxide compare to that of oxygen with hemoglobin?

    <p>Carbon monoxide binds more effectively than oxygen.</p> Signup and view all the answers

    What effect do barbiturates have on the respiratory chain?

    <p>They act as inhibitors of respiration.</p> Signup and view all the answers

    In which compartment of the cell does oxidative phosphorylation primarily occur?

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

    Which statement accurately describes the function of the mitochondrial respiratory chain?

    <p>It facilitates the transfer of electrons to produce ATP.</p> Signup and view all the answers

    What is the main consequence of inhibiting Complex IV?

    <p>Decreased oxygen utilization.</p> Signup and view all the answers

    What role do inhibitors of the respiratory chain play in cellular metabolism?

    <p>They decrease ATP generation.</p> Signup and view all the answers

    What is the main purpose of the citric acid cycle?

    <p>To harvest high-energy electrons from carbon fuels</p> Signup and view all the answers

    Which intermediate is formed from acetyl-CoA during the citric acid cycle?

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

    What is the significance of the oxidation of malate to oxaloacetate in the cycle?

    <p>It is a reversible reaction</p> Signup and view all the answers

    Which product is formed during the oxidative decarboxylation of α-ketoglutarate?

    <p>Succinyl-CoA</p> Signup and view all the answers

    What is the Gibbs free energy change (ΔG°ˊ) for the formation of citrate from oxaloacetate?

    <p>−32.2 kJ/mol</p> Signup and view all the answers

    Which vitamin is NOT mentioned as a cofactor in the oxidative decarboxylation process?

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

    Why is the reaction from malate to oxaloacetate driven forward in intact cells?

    <p>Oxaloacetate is continually removed by another reaction</p> Signup and view all the answers

    Which of the following is NOT an intermediate of the TCA cycle?

    <p>Acetyl-CoA</p> Signup and view all the answers

    What type of reaction is the conversion of citrate to isocitrate?

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

    What is the main role of anaplerotic reactions in the TCA cycle?

    <p>To replenish intermediates that are depleted</p> Signup and view all the answers

    Which statement correctly describes the electron transport chain?

    <p>It reduces oxygen to form water</p> Signup and view all the answers

    How many protons are required to drive the synthesis of one ATP according to the chemiosmotic hypothesis?

    <p>4 protons</p> Signup and view all the answers

    What is the function of cytochrome c in the electron transport chain?

    <p>Carries one electron between complexes</p> Signup and view all the answers

    Why does FADH2 produce less ATP compared to NADH in the electron transport chain?

    <p>It enters the chain at a later stage</p> Signup and view all the answers

    What is the primary control mechanism for the activity of the electron transport chain?

    <p>Concentration of ADP and ATP</p> Signup and view all the answers

    Which compound serves as a mobile electron carrier in the electron transport chain?

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

    Which process involves the coupling of electron transport to ATP synthesis?

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

    What is produced as a byproduct of glucose oxidation in cellular respiration?

    <p>Carbon dioxide and water</p> Signup and view all the answers

    What type of metabolic pathway does the TCA cycle represent?

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

    Which molecule is primarily responsible for carrying reducing equivalents in the respiratory chain?

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

    What happens to electron carriers in the electron transport chain after they donate their electrons?

    <p>They are recycled back to their original state</p> Signup and view all the answers

    What role does ATP synthase play in cellular respiration?

    <p>It synthesizes ATP using a proton gradient</p> Signup and view all the answers

    Where does oxidative phosphorylation primarily occur within the cell?

    <p>Inner mitochondrial membrane</p> Signup and view all the answers

    What is the final electron acceptor in the electron transport chain?

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

    What is the role of the glycerophosphate shuttle in cellular metabolism?

    <p>It transfers reducing equivalents from cytosol to the mitochondrial matrix.</p> Signup and view all the answers

    What is the primary effect of 2,4-DNP in the body?

    <p>It disrupts the proton gradient across the mitochondrial membrane.</p> Signup and view all the answers

    Which shuttle utilizes the cytosolic and mitochondrial isoforms of malate dehydrogenase?

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

    Superoxide dismutase plays a crucial role in the detoxification of which type of reactive species?

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

    Which metabolic pathway is primarily affected by the inhibition of ATP synthase?

    <p>Oxidative phosphorylation</p> Signup and view all the answers

    What is a significant consequence of generating heat in brown adipose tissue?

    <p>Thermogenesis without ATP generation</p> Signup and view all the answers

    Which enzyme is responsible for transaminating glutamate to form aspartate?

    <p>Aspartate aminotransferase</p> Signup and view all the answers

    How many molecules of ATP are produced when glucose is fully oxidized?

    <p>32 ATP per molecule of glucose</p> Signup and view all the answers

    The malate shuttle is primarily utilized for transporting which type of equivalents?

    <p>Reducing equivalents</p> Signup and view all the answers

    What mechanism allows 2,4-DNP to promote weight loss?

    <p>By uncoupling oxidative phosphorylation</p> Signup and view all the answers

    Study Notes

    Pyruvate Oxidation

    • Pyruvate is oxidized to acetyl-CoA and CO2 inside the mitochondria
    • Pyruvate dehydrogenase complex (PDHc) is responsible for this process
    • PDHc contains three enzymes: E1, E2, and E3
    • Four water-soluble vitamins are crucial for pyruvate oxidation: thiamin, riboflavin, niacin, and pantothenic acid
    • Lipoate is also involved in the process
    • PDH is regulated by allosteric effectors and covalent modification
    • Deficiencies or dysregulation of PDHc can have clinical significance

    TCA Cycle

    • Acetyl-CoA is oxidized in the TCA cycle to generate CO2, reducing equivalents (NADH & FADH2), and GTP
    • The cycle consists of eight enzymatic steps:
      • Citrate synthase catalyzes the formation of citrate from oxaloacetate and acetyl-CoA
      • Aconitase converts citrate to isocitrate
      • Isocitrate dehydrogenase oxidizes isocitrate while forming NADH and CO2
      • Alpha-ketoglutarate dehydrogenase complex (α-KGDH) is similar to PDHc and catalyzes the formation of succinyl-CoA, NADH, and CO2
      • Succinyl-CoA synthetase converts succinyl-CoA to succinate, producing GTP
      • Succinate dehydrogenase catalyzes the oxidation of succinate to fumarate, producing FADH2
      • Fumarase converts fumarate to malate
      • Malate dehydrogenase produces oxaloacetate from malate, generating NADH
    • The cycle is highly exergonic and thermodynamically favorable
    • The TCA cycle is regulated by substrate availability and allosteric effectors
    • Dysregulation of TCA cycle enzymes, such as SDH, can have clinical significance

    Oxidative Phosphorylation and ETC

    • Four protein complexes (I, II, III, IV) and mobile electron carriers (Q & cytochrome c) are involved in the ETC
    • The respiratory chain oxidizes reducing equivalents (NADH and FADH2), acting as a proton pump
    • The chemiosmotic theory explains ATP synthesis through proton gradient generation across the inner mitochondrial membrane
    • Inhibitors can block specific steps in the ETC or oxidative phosphorylation, including rotenone, cyanide, antimycin A, and oligomycin
    • The glycerol phosphate shuttle and malate-aspartate shuttle transfer reducing equivalents from the cytoplasm to the mitochondria
    • Superoxide dismutase protects the ETC from oxidative damage

    Electron Transport Chain

    • The ETC (respiratory chain) involves the sequential transfer of electrons from NADH or FADH2 to oxygen
    • Complex I (NADH-Q oxidoreductase) receives electrons from NADH and transfers them to Q
    • Complex II (succinate-Q reductase) receives electrons from FADH2 and transfers them to Q
    • Complex III (Q-cytochrome c oxidoreductase) accepts electrons from Q and passes them to cytochrome c
    • Complex IV (cytochrome c oxidase) receives electrons from cytochrome c and transfers them to oxygen, producing water

    Oxidative Phosphorylation

    • The proton gradient generated by the ETC drives ATP synthesis
    • ATP synthase uses the gradient to phosphorylate ADP to ATP
    • The ETC and oxidative phosphorylation generate ATP efficiently from glucose oxidation
    • FADH2 produces less ATP than NADH due to its entry point in the ETC

    Amphibolic Nature of TCA

    • The TCA cycle is amphibolic, meaning it plays roles in both energy production and biosynthetic pathways, including gluconeogenesis, amino acid synthesis, and fatty acid synthesis
    • Anaplerotic reactions replenish TCA cycle intermediates, ensuring its continuous operation### ATP Synthase
    • Inhibits oxidation and phosphorylation by blocking proton flow through ATP synthase.

    Glycerol 3-phosphate Shuttle

    • Transfers reducing equivalents from cytosol to mitochondrial matrix
    • Utilizes cytosolic and mitochondrial isoforms of Glycerol-3-P DH.

    Malate Shuttle

    • Transfers reducing equivalents from cytosol to mitochondrial matrix.
    • Utilizes cytosolic and mitochondrial isoforms of Malate DH.
    • The same enzyme but different locations.

    Glutamate-Oxaloacetate Transaminase

    • Also known as Aspartate aminotransferase.
    • Transports reducing equivalents from cytosol to mitochondrial matrix.

    Brown Adipose Tissue

    • Rich in mitochondria to generate heat (thermogenesis).
    • 2,4-Dinitrophenol (2,4-DNP) increases uncoupling in brown adipose tissue.
    • Increases mitochondrial permeability and reduces ATP synthesis, leading to increased heat production.

    Superoxide Dismutase

    • Neutralizes superoxide radicals (O2-)
    • Superoxide radicals are reactive oxygen species.

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    Explore the intricacies of pyruvate oxidation and the TCA cycle in this quiz. Focus on the key processes, enzymes involved, and the importance of specific vitamins in energy metabolism. Test your understanding of metabolic pathways and their regulation.

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