The Citric Acid Cycle and Pyruvate Dehydrogenase Complex Quiz
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Questions and Answers

What is the primary catabolic purpose of the citric acid cycle?

  • To synthesize amino acids for protein biosynthesis
  • To produce ATP directly through substrate-level phosphorylation
  • To convert pyruvate to lactate in anaerobic conditions
  • To generate reduced coenzymes for the electron transport chain (correct)

    • What is the role of the pyruvate dehydrogenase complex?

  • To convert pyruvate to acetyl CoA for entry into the citric acid cycle (correct)
  • To convert glucose to pyruvate in glycolysis
  • To synthesize lipids for cell membrane formation
  • To produce ATP through oxidative phosphorylation

    • What is the biochemical advantage provided by the glyoxylate cycle?

  • Facilitating the conversion of pyruvate to lactate in anaerobic conditions
  • Promoting the synthesis of glycogen for energy storage
  • Enhancing the efficiency of ATP production in the citric acid cycle
  • Enabling plants and bacteria to grow on acetate (correct)

    • How is the citric acid cycle regulated?

    <p>Through feedback inhibition by high levels of ATP and NADH</p> Signup and view all the answers

    What is the function of E2 in the Pyruvate Dehydrogenase Complex (PDC)?

    <p>Inserts lipoamide arm into E1 channel for acetyl group transfer</p> Signup and view all the answers

    What is the product of the oxidation of lipoamide by coenzyme FAD in the Pyruvate Dehydrogenase Complex (PDC)?

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

    What is the role of aconitase in cellular metabolism?

    <p>Catalyzes isomerization of citrate into isocitrate</p> Signup and view all the answers

    What is the homologous relationship between α-ketoglutarate dehydrogenase complex and Pyruvate Dehydrogenase Complex (PDC)?

    <p>Both are involved in oxidative decarboxylation of a specific molecule</p> Signup and view all the answers

    Which factor promotes pyruvate dehydrogenase complex phosphorylation and inactivation?

    <p>Epinephrine and insulin</p> Signup and view all the answers

    What may be a consequence of pyruvate dehydrogenase phosphatase deficiency?

    <p>Lactic acidosis and tissue malfunction</p> Signup and view all the answers

    What effect does hyperglycemia have on the pyruvate dehydrogenase complex?

    <p>Increases PDK activity, leading to inhibition of the complex</p> Signup and view all the answers

    Which compounds bind to the E3 component and inhibit the pyruvate dehydrogenase complex?

    <p>Mercury and arsenite</p> Signup and view all the answers

    Which enzyme catalyzes the decarboxylation of isocitrate in the citric acid cycle?

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

    What is the principal fate of Acetyl CoA?

    <p>Metabolism by the citric acid cycle</p> Signup and view all the answers

    How is the pyruvate dehydrogenase complex regulated?

    <p>Allosterically and by reversible phosphorylation</p> Signup and view all the answers

    How many molecules of ATP are approximately generated from one cycle of the citric acid cycle?

    <p>10</p> Signup and view all the answers

    Which enzyme catalyzes the rate-limiting step in acetyl CoA synthesis within the pyruvate dehydrogenase complex?

    <p>E1</p> Signup and view all the answers

    What is the main role of lipoamide in the pyruvate dehydrogenase complex?

    <p>Carrying substrates between active sites and increasing the overall reaction rate</p> Signup and view all the answers

    What is the core composition of the pyruvate dehydrogenase complex in mammals?

    <p>E1 as an α2β2 tetramer, E3 as an αβ dimer, and E3-binding protein (E3-BP)</p> Signup and view all the answers

    Which step of the pyruvate dehydrogenase complex involves the transfer of the hydroxyethyl group to lipoamide?

    <p>Oxidation step</p> Signup and view all the answers

    Which enzyme catalyzes the decarboxylation of isocitrate in the citric acid cycle?

    <p>Isocitrate lyase</p> Signup and view all the answers

    What is the principal fate of Acetyl CoA?

    <p>Incorporation into lipids</p> Signup and view all the answers

    How many molecules of ATP are approximately generated from one cycle of the citric acid cycle?

    <p>10</p> Signup and view all the answers

    What is the role of the pyruvate dehydrogenase complex?

    <p>Conversion of pyruvate to acetyl-CoA</p> Signup and view all the answers

    How is the pyruvate dehydrogenase complex regulated?

    <p>Allosterically and by reversible phosphorylation</p> Signup and view all the answers

    What is the product of the oxidation of lipoamide by coenzyme FAD in the Pyruvate Dehydrogenase Complex (PDC)?

    <p>FADH2</p> Signup and view all the answers

    What is the main entry point for fuel molecules into the citric acid cycle?

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

    Which coenzyme is involved in the conversion of pyruvate into acetyl CoA?

    <p>Thiamine pyrophosphate (TPP)</p> Signup and view all the answers

    What is the role of lipoamide in the pyruvate dehydrogenase complex?

    <p>Carrying substrates between active sites and increasing the overall reaction rate</p> Signup and view all the answers

    What is the core composition of the pyruvate dehydrogenase complex in mammals?

    <p>E1 as an α2β2 tetramer, E3 as an αβ dimer, and E3-binding protein (E3-BP)</p> Signup and view all the answers

    What is the function of the E2 component in the Pyruvate Dehydrogenase Complex (PDC)?

    <p>Transferring the acetyl group to CoA to form acetyl CoA</p> Signup and view all the answers

    What is the rate-limiting step in acetyl CoA synthesis within the pyruvate dehydrogenase complex?

    <p>Decarboxylation of pyruvate</p> Signup and view all the answers

    What is the function of E1 in the Pyruvate Dehydrogenase Complex (PDC)?

    <p>Catalyzes acetyl group transfer to lipoamide</p> Signup and view all the answers

    What is the primary role of citrate synthase in the citric acid cycle?

    <p>Catalyzes addition of acetyl CoA and oxaloacetate</p> Signup and view all the answers

    What is the function of aconitase in cellular metabolism?

    <p>Catalyzes isomerization of citrate into isocitrate</p> Signup and view all the answers

    What is the role of isocitrate dehydrogenase in the citric acid cycle?

    <p>Catalyzes oxidative decarboxylation of isocitrate to $\alpha$-ketoglutarate</p> Signup and view all the answers

    What is the homologous relationship between the $eta$-ketoglutarate dehydrogenase complex and Pyruvate Dehydrogenase Complex (PDC)?

    <p>Both are homologous multienzyme complexes involved in oxidative decarboxylation</p> Signup and view all the answers

    What is the primary function of succinyl CoA synthetase in the citric acid cycle?

    <p>Generates succinate and can couple with ATP or GTP formation</p> Signup and view all the answers

    What is the consequence of pyruvate dehydrogenase phosphatase deficiency?

    <p>Lactic acidosis and tissue malfunction</p> Signup and view all the answers

    What is the effect of hyperglycemia on the pyruvate dehydrogenase complex?

    <p>Increases PDK activity, leading to inhibition of the pyruvate dehydrogenase complex</p> Signup and view all the answers

    What is the role of Ca2+ in regulating pyruvate dehydrogenase activity?

    <p>Stimulates the phosphatase, enhancing pyruvate dehydrogenase activity</p> Signup and view all the answers

    What is the consequence of mercury and arsenite inhibition of the pyruvate dehydrogenase complex?

    <p>Central nervous system pathologies</p> Signup and view all the answers

    What is the consequence of thiamine deficiency causing disruption of pyruvate metabolism?

    <p>Higher levels of pyruvate and α-ketoglutarate in the blood</p> Signup and view all the answers

    What is the consequence of diabetic neuropathy due to inhibition of the pyruvate dehydrogenase complex?

    <p>Numbness, tingling, or pain</p> Signup and view all the answers

    What is the primary catabolic purpose of the citric acid cycle?

    <p>To produce NADH and FADH$_2$ for the electron transport chain</p> Signup and view all the answers

    What is the role of the pyruvate dehydrogenase complex?

    <p>To convert pyruvate to acetyl CoA for entry into the citric acid cycle</p> Signup and view all the answers

    What is the main advantage provided by the glyoxylate cycle?

    <p>Enables plants and bacteria to grow on acetate</p> Signup and view all the answers

    How is the citric acid cycle regulated?

    <p>Through feedback inhibition by ATP and NADH</p> Signup and view all the answers

    What is the efficiency of using the citric acid cycle to oxidize acetyl CoA?

    <p>High efficiency due to the production of NADH and FADH$_2$</p> Signup and view all the answers

    What is the crucial juncture in metabolism catalyzed by the pyruvate dehydrogenase complex?

    <p>Conversion of pyruvate to acetyl CoA</p> Signup and view all the answers

    What is the crucial juncture in metabolism catalyzed by the pyruvate dehydrogenase complex?

    <p>Conversion of pyruvate to acetyl CoA</p> Signup and view all the answers

    What is the primary catabolic purpose of the citric acid cycle?

    <p>To generate reducing equivalents for oxidative phosphorylation</p> Signup and view all the answers

    How is the citric acid cycle regulated?

    <p>By feedback inhibition from ATP and NADH</p> Signup and view all the answers

    What is the efficiency of using the citric acid cycle to oxidize acetyl CoA?

    <p>$ ext{38 ATP}$ per molecule of acetyl CoA</p> Signup and view all the answers

    What is the role of the citric acid cycle in biosynthesis?

    <p>Providing precursors for the synthesis of amino acids and nucleotides</p> Signup and view all the answers

    What are the means by which the pyruvate dehydrogenase complex is regulated?

    <p>Regulation by feedback inhibition from ATP and NADH</p> Signup and view all the answers

    What is the net reaction of the citric acid cycle?

    <p>Generation of ATP, CO2, NADH, FADH2, and consumption of water</p> Signup and view all the answers

    Which enzyme catalyzes the hydration of fumarate to L-malate in the citric acid cycle?

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

    What is the primary fate of Acetyl CoA in animal cells?

    <p>Metabolism by the citric acid cycle or incorporation into lipids</p> Signup and view all the answers

    What regulates the pyruvate dehydrogenase complex allosterically?

    <p>Changes in the energy charge of the cell</p> Signup and view all the answers

    How many carbon atoms from acetyl CoA leave the citric acid cycle as CO2?

    <p>$2$</p> Signup and view all the answers

    What is the role of succinate dehydrogenase in cellular metabolism?

    <p>Embedded in the inner mitochondrial membrane and directly associated with the electron-transport chain</p> Signup and view all the answers

    Where does the citric acid cycle take place?

    <p>Mitochondrial matrix</p> Signup and view all the answers

    What is the primary entry point for fuel molecules into the citric acid cycle?

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

    Which enzyme catalyzes the irreversible link between glycolysis and the citric acid cycle?

    <p>Pyruvate dehydrogenase complex</p> Signup and view all the answers

    Which coenzyme is required for the conversion of pyruvate to acetyl CoA?

    <p>$TPP$ (thiamine pyrophosphate)</p> Signup and view all the answers

    What is the rate-limiting step in the conversion of pyruvate to acetyl CoA?

    <p>$eta$-decarboxylation</p> Signup and view all the answers

    What is the role of lipoamide in the pyruvate dehydrogenase complex?

    <p>Transferring hydroxyethyl group to lipoamide</p> Signup and view all the answers

    What regulates the pyruvate dehydrogenase complex allosterically?

    <p>ADP and pyruvate</p> Signup and view all the answers

    What is the consequence of thiamine deficiency causing disruption of pyruvate metabolism?

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

    How is the citric acid cycle regulated?

    <p>$Ca^{2+}$ and phosphatase</p> Signup and view all the answers

    What is the consequence of mercury and arsenite inhibition of the pyruvate dehydrogenase complex?

    <p>Central nervous system pathologies</p> Signup and view all the answers

    What is the primary catabolic purpose of the citric acid cycle?

    <p>To generate NADH and FADH$_2$ for oxidative phosphorylation</p> Signup and view all the answers

    What is the role of lipoamide in the pyruvate dehydrogenase complex?

    <p>To transfer acetyl groups between enzyme active sites</p> Signup and view all the answers

    What is the role of citrate synthase in the citric acid cycle?

    <p>Catalyzes addition of acetyl CoA and oxaloacetate to yield citrate and CoA</p> Signup and view all the answers

    What is the function of aconitase in the citric acid cycle?

    <p>Catalyzes isomerization of citrate into isocitrate through dehydration and hydration steps</p> Signup and view all the answers

    What is the primary function of succinyl CoA synthetase in the citric acid cycle?

    <p>Catalyzes cleavage of thioester linkage of succinyl CoA to yield succinate</p> Signup and view all the answers

    What is the role of α-ketoglutarate dehydrogenase complex in the citric acid cycle?

    <p>Catalyzes oxidative decarboxylation of α-ketoglutarate to succinyl CoA</p> Signup and view all the answers

    What is the consequence of thiamine deficiency causing disruption of pyruvate metabolism?

    <p>Decreased production of ATP</p> Signup and view all the answers

    Study Notes

    The Citric Acid Cycle and Pyruvate Dehydrogenase Complex

    • The citric acid cycle (CAC) is a series of oxidation-reduction reactions that oxidize an acetyl group to two molecules of CO2, generating high-energy electrons for ATP synthesis and biosynthesis.
    • Acetyl CoA is the main entry point for fuel molecules into the citric acid cycle.
    • The pyruvate dehydrogenase complex oxidatively decarboxylates pyruvate to acetyl CoA, and the reactions take place in the mitochondrial matrix.
    • The citric acid cycle removes electrons from acetyl CoA to produce NADH and FADH2, which then enter the electron-transport chain to generate a proton gradient for ATP synthesis.
    • The pyruvate dehydrogenase complex links glycolysis to the citric acid cycle and consists of three distinct enzymes.
    • The conversion of pyruvate into acetyl CoA involves three steps and five coenzymes, including thiamine pyrophosphate (TPP), lipoic acid, and FAD.
    • The decarboxylation step of pyruvate is the rate-limiting step in acetyl CoA synthesis and is catalyzed by the pyruvate dehydrogenase component (E1) of the complex.
    • The oxidation step of the pyruvate dehydrogenase complex involves the transfer of the hydroxyethyl group to lipoamide, forming acetyllipoamide, and the subsequent formation of acetyl CoA.
    • The regeneration of oxidized lipoamide in the complex involves the transfer of two electrons to an FAD prosthetic group and then to NAD+.
    • Lipoamide, a derivative of lipoic acid, plays a crucial role in the pyruvate dehydrogenase complex by carrying substrates between active sites and increasing the overall reaction rate.
    • The core of the pyruvate dehydrogenase complex is formed by 60 molecules of the transacetylase subunit, which consists of 20 catalytic trimers assembled to form a hollow cube.
    • In mammals, the pyruvate dehydrogenase complex consists of E1 as an α2β2 tetramer, E3 as an αβ dimer, and E3-binding protein (E3-BP) to facilitate the interaction between E2 and E3.

    Pyruvate Dehydrogenase Complex Regulation and Dysfunction

    • Pyruvate dehydrogenase complex phosphorylation and inactivation is promoted by PDK activation, while high ADP and pyruvate activate the complex by inhibiting the kinase.
    • Ca2+ stimulates the phosphatase, enhancing pyruvate dehydrogenase activity.
    • In liver tissue, epinephrine and insulin regulate the phosphatase, affecting Ca2+ concentration and pyruvate dehydrogenase activity.
    • Individuals with pyruvate dehydrogenase phosphatase deficiency have inactive pyruvate dehydrogenase complex, leading to lactic acidosis and tissue malfunction.
    • Diabetic neuropathy, a common complication of diabetes, may be due to inhibition of the pyruvate dehydrogenase complex, resulting in numbness, tingling, or pain.
    • Hyperglycemia increases PDK activity, leading to inhibition of the pyruvate dehydrogenase complex and subsequent lactic acid overproduction in diabetic neuropathy.
    • The citric acid cycle is regulated by several allosteric enzymes, including isocitrate dehydrogenase and α-ketoglutarate dehydrogenase.
    • The citric acid cycle integrates the cell's metabolic pathways and plays an important role in biosynthesis of key biomolecules.
    • Citric acid cycle intermediates must be rapidly replenished through anaplerotic reactions, as mammals lack enzymes for net conversion of acetyl CoA into cycle intermediates.
    • Beriberi, caused by thiamine deficiency, disrupts pyruvate metabolism and leads to higher levels of pyruvate and α-ketoglutarate in the blood.
    • Mercury and arsenite inhibit the pyruvate dehydrogenase complex by binding to the E3 component, leading to central nervous system pathologies.
    • The citric acid cycle likely evolved from preexisting pathways, with compounds like pyruvate and α-ketoglutarate present early in evolution for biosynthetic purposes.

    Citric Acid Cycle and Pyruvate Dehydrogenase Mechanism Explained

    • Pyruvate Dehydrogenase Complex involves 6 steps: E2 inserts lipoamide arm into E1, E1 transfers acetyl group to lipoamide, acetyl moiety transfers to CoA, reduced lipoamide arm swings to E3 flavoprotein, lipoamide is oxidized by coenzyme FAD, NADH is produced.
    • Citrate synthase catalyzes addition of acetyl CoA and oxaloacetate, yielding citrate and CoA through aldol addition and hydrolysis, proceeds through energy-rich citryl CoA.
    • Citrate synthase minimizes hydrolysis of acetyl CoA to acetate and CoA, exhibits sequential, ordered kinetics, and has active sites in a cleft between subunit domains.
    • Citrate synthase mechanism involves conformational changes upon binding oxaloacetate, with His 274 promoting enol intermediate formation and hydrolysis of thioester to yield citrate and CoA.
    • Aconitase catalyzes isomerization of citrate into isocitrate through dehydration and hydration steps, with citrate binding directly to iron-sulfur complex.
    • Isocitrate dehydrogenase catalyzes oxidative decarboxylation of isocitrate to form α-ketoglutarate and NADH, proceeds through unstable oxalosuccinate and releases CO2 to yield α-ketoglutarate.
    • α-Ketoglutarate dehydrogenase complex catalyzes oxidative decarboxylation of α-ketoglutarate to succinyl CoA, yielding NADH, and has entirely analogous mechanisms to pyruvate dehydrogenase complex.
    • Succinyl CoA synthetase catalyzes cleavage of thioester linkage of succinyl CoA to yield succinate, coupled to phosphorylation of ADP or GDP, with readily reversible reaction.
    • Mammals have two isozymic forms of succinyl CoA synthetase: GDP-requiring enzyme in anabolic tissues and ADP-requiring enzyme in tissues performing cellular respiration.
    • Nucleoside diphosphokinase allows adjustment of nucleotide triphosphate and diphosphate concentrations to meet cell's needs and maintain equilibrium.
    • Succinyl CoA synthetase transforms energy inherent in thioester molecule into phosphoryl-group-transfer potential, with a ∆G°′ of −3.4 kJ mol−1, and allows formation of ATP through substrate-level phosphorylation.
    • Succinyl CoA synthetase mechanism involves orthophosphate attacking succinyl CoA to displace coenzyme A and generate succinyl phosphate, an energy-rich compound.

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    Test your knowledge of the citric acid cycle and pyruvate dehydrogenase complex with this quiz. Explore the key steps, enzymes, and coenzymes involved in these critical metabolic pathways, and deepen your understanding of how cells generate energy from fuel molecules.

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