Harper's Biochemistry Chapter 17 - Glycolysis & the Oxidation of Pyruvate
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Questions and Answers

What is the effect of increased [ATP]/[ADP] on kinase activation?

  • It has no effect on the kinase.
  • It activates the kinase. (correct)
  • It reverses the function of the kinase.
  • It inhibits the kinase.

    • How does 2,3-bisphosphoglycerate affect hemoglobin's function?

  • It decreases hemoglobin's affinity for oxygen. (correct)
  • It has no effect on hemoglobin's oxygen affinity.
  • It increases the efficiency of oxygen uptake only.
  • It increases hemoglobin's affinity for oxygen.

    • What happens to glycolysis when there are elevated fatty acid levels?

  • Pyruvate is oxidized more rapidly.
  • Pyruvate oxidation decreases. (correct)
  • Glycolysis is stimulated.
  • ATP levels increase significantly.

    • Which enzyme is responsible for the conversion of pyruvate to acetyl-CoA?

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

    What condition can lead to lactic acidosis as a result of pyruvate accumulation?

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

    What is the role of NADH in the glycolytic pathway?

    <p>It helps regenerate NAD+ for glycolysis.</p> Signup and view all the answers

    Which process does not yield any net ATP from glycolysis?

    <p>Conversion of 1,3-bisphosphoglycerate to 2,3-bisphosphoglycerate</p> Signup and view all the answers

    What triggers the activation of the enzyme responsible for lipogenesis in adipose tissue?

    <p>Insulin signaling</p> Signup and view all the answers

    What is one consequence of inhibition of pyruvate oxidation?

    <p>Development of lactic acidosis</p> Signup and view all the answers

    Which condition is most likely to affect the ability to metabolize lactate?

    <p>Thiamin deficiency</p> Signup and view all the answers

    What is the primary role of NADH in glycolysis?

    <p>To regenerate NAD+ for continued glycolysis</p> Signup and view all the answers

    Which enzyme is involved in the regulation of the glycolytic pathway?

    <p>All of the above</p> Signup and view all the answers

    Under what condition does glycolysis primarily provide ATP?

    <p>In the absence of oxygen</p> Signup and view all the answers

    What indicates allosteric effects in metabolic regulation?

    <p>Wavy arrows</p> Signup and view all the answers

    Which regulation involves the inhibition of an enzyme by its end product?

    <p>Feedback inhibition</p> Signup and view all the answers

    Under anaerobic conditions, which compound is produced from pyruvate?

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

    Which cofactor is essential for the pyruvate dehydrogenase complex?

    <p>Thiamin diphosphate</p> Signup and view all the answers

    Which enzyme catalyzes a key step in glycolysis and is subject to allosteric regulation?

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

    What is one of the results of inherited pyruvate kinase deficiency?

    <p>Hemolytic anemia</p> Signup and view all the answers

    What role does NAD+ play in the glycolytic pathway?

    <p>Regenerates during glycolysis for oxidation of glucose</p> Signup and view all the answers

    Which metabolic consequence is likely from impaired pyruvate metabolism?

    <p>Neurologic disturbances</p> Signup and view all the answers

    Which enzyme is NOT involved in catalyzing nonequilibrium reactions in glycolysis?

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

    What compound can bypass the first ATP-generating step in glycolysis in erythrocytes?

    <p>2,3-bisphosphoglycerate</p> Signup and view all the answers

    What is the primary outcome when pyruvate oxidation is impaired in certain tissues?

    <p>Pyruvate is diverted to lactate.</p> Signup and view all the answers

    Which enzyme is NOT involved in the gluconeogenesis pathway?

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

    How does insulin influence the regulation of glycolysis and gluconeogenesis?

    <p>It promotes glycolysis over gluconeogenesis.</p> Signup and view all the answers

    What is the role of NAD in glycolysis during hypoxic conditions?

    <p>It is recycled to support glycolysis.</p> Signup and view all the answers

    Which condition describes the cause for lactate production in erythrocytes?

    <p>Absence of mitochondria.</p> Signup and view all the answers

    How does fructose metabolism differ from glucose metabolism in terms of regulatory steps?

    <p>Fructose bypasses the main regulatory steps of glycolysis.</p> Signup and view all the answers

    Which of the following enzymes is crucial for the conversion of pyruvate to glucose in gluconeogenesis?

    <p>Phosphoenolpyruvate carboxykinase</p> Signup and view all the answers

    What major metabolic imbalance can occur in tissues with a high rate of anaerobic glycolysis?

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

    Which factor limits pyruvate oxidation in specific muscle fibers during high work output?

    <p>Reduced oxygen delivery</p> Signup and view all the answers

    What effect do the products acetyl-CoA and NADH have on pyruvate dehydrogenase?

    <p>They inhibit its activity.</p> Signup and view all the answers

    How does phosphorylation affect the activity of pyruvate dehydrogenase?

    <p>It decreases the enzyme's activity.</p> Signup and view all the answers

    What role does NAD+ play in the reaction catalyzed by the reduced flavoprotein?

    <p>It is transformed into NADH.</p> Signup and view all the answers

    What is the main benefit of the intermediates being channeled in the pyruvate dehydrogenase complex?

    <p>Increases the rate of reaction and prevents side reactions.</p> Signup and view all the answers

    In the context of glycolysis, which compound is produced alongside NADH during the conversion of pyruvate?

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

    Which enzyme is responsible for dephosphorylation of pyruvate dehydrogenase in order to increase its activity?

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

    What is produced as a byproduct of the pyruvate dehydrogenase reaction aside from NADH and acetyl-CoA?

    <p>CO2</p> Signup and view all the answers

    Which metabolic condition may bypass the first site of ATP formation in erythrocytes?

    <p>Anaerobic glycolysis</p> Signup and view all the answers

    Which of the following statements about the pyruvate dehydrogenase complex is false?

    <p>Intermediates can dissociate from the active sites.</p> Signup and view all the answers

    What type of chemical modification is indicated for regulating pyruvate dehydrogenase activity?

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

    How does inherited aldolase A deficiency primarily affect erythrocytes?

    <p>It causes hemolytic anemia due to inefficient glycolysis.</p> Signup and view all the answers

    What is the primary consequence of impaired pyruvate metabolism in tissues?

    <p>Development of lactic acidosis due to excess pyruvate.</p> Signup and view all the answers

    Which enzyme catalyzing a nonequilibrium reaction in glycolysis is primarily affected by glucose transport regulation?

    <p>Hexokinase.</p> Signup and view all the answers

    In which condition is lactate produced from pyruvate mainly observed?

    <p>Under anaerobic conditions such as in exercising muscle.</p> Signup and view all the answers

    What is the critical function of 2,3-bisphosphoglycerate in erythrocytes?

    <p>To decrease the affinity of hemoglobin for O2.</p> Signup and view all the answers

    What is the main advantage of using glycogen over glucose for anaerobic glycolysis in muscle?

    <p>Glycogen phosphorylase yields glucose-1-phosphate, saving ATP.</p> Signup and view all the answers

    How many moles of ATP are produced per mole of glucose when glycogen is utilized?

    <p>3 ATP</p> Signup and view all the answers

    What is the final product of anaerobic glycolysis when glucose is metabolized?

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

    What does the glycerophosphate shuttle yield in terms of ATP production?

    <p>1.5 ATP per NADH</p> Signup and view all the answers

    Which enzyme facilitates the conversion of glucose-1-phosphate to glucose-6-phosphate?

    <p>Phosphohexose isomerase</p> Signup and view all the answers

    In terms of ATP consumption, what is significant about the initial formation of glycogen?

    <p>It consumes ATP initially but saves it during glycolysis.</p> Signup and view all the answers

    What role does glucose-6-phosphate play in glycolysis?

    <p>It regulates the flux through glycolysis.</p> Signup and view all the answers

    Which molecule acts as a precursor leading to the production of pyruvate in glycolysis?

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

    What is the main function of glycogen phosphorylase in glycolysis?

    <p>To yield glucose-1-phosphate from glycogen.</p> Signup and view all the answers

    What happens to ATP levels when glycogen is converted to glucose-1-phosphate for anaerobic glycolysis?

    <p>More ATP is generated than consumed.</p> Signup and view all the answers

    What pathway does pyruvate follow under anaerobic conditions?

    <p>Reduction to lactate</p> Signup and view all the answers

    Which enzyme is primarily responsible for the regulation of glycolysis at non-equilibrium reactions?

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

    What determines the pathway that pyruvate follows?

    <p>Availability of oxygen</p> Signup and view all the answers

    In the presence of high ATP concentrations, which glycolytic enzyme is significantly inhibited?

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

    How is NADH reoxidized under aerobic conditions?

    <p>Through the glycerophosphate shuttle</p> Signup and view all the answers

    What is the effect of accumulating ADP in a cell?

    <p>Activation of phosphofructokinase</p> Signup and view all the answers

    What happens to pyruvate in the mitochondria under aerobic conditions?

    <p>It is transported and decarboxylated to acetyl-CoA</p> Signup and view all the answers

    Which of the following shuttles is involved in transferring reducing equivalents into mitochondria?

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

    Why is lactate produced in tissues functioning under hypoxic conditions?

    <p>Due to a lack of sufficient oxygen for pyruvate conversion</p> Signup and view all the answers

    What is the metabolic consequence of a failure to oxidize NADH in the cytosol?

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

    What property of lipoic acid contributes to its function in the enzyme complex?

    <p>It possesses a long flexible arm.</p> Signup and view all the answers

    Which ion is essential for the activity of PDH phosphatase?

    <p>Magnesium (Mg2+)</p> Signup and view all the answers

    What is the primary functional consequence of the amide link of lipoic acid to the enzyme?

    <p>Enables sequential rotation between active sites.</p> Signup and view all the answers

    What happens to pyruvate dehydrogenase (PDH) when it is phosphorylated?

    <p>It is inhibited.</p> Signup and view all the answers

    How do NADH and acetyl-CoA influence pyruvate dehydrogenase activity?

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

    Which regulatory mechanism is indicated for the activation of the PDH complex?

    <p>Insulin signaling in adipose tissue.</p> Signup and view all the answers

    What role does Ca2+ play in the regulation of pyruvate dehydrogenase?

    <p>It stimulates PDH activity indirectly.</p> Signup and view all the answers

    What molecule acts as a substrate for the PDH complex alongside pyruvate?

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

    Which component is NOT a product of the pyruvate dehydrogenase reaction?

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

    What effect does dichloroacetate have on pyruvate metabolism?

    <p>Activates PDH by inhibiting the PDH kinase.</p> Signup and view all the answers

    What occurs in cancer cells as a result of high rates of glycolysis under anaerobic conditions?

    <p>Pyruvate is reduced to lactate to regenerate NAD.</p> Signup and view all the answers

    What is a consequence of mitochondrial reoxidation of NADH being impaired due to low oxygen availability?

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

    What is one of the main limitations of glycolysis when operating under anaerobic conditions?

    <p>It leads to high levels of glucose consumption for ATP generation.</p> Signup and view all the answers

    In yeast and some microorganisms, what happens to pyruvate formed during anaerobic glycolysis?

    <p>It is decarboxylated and subsequently reduced to ethanol.</p> Signup and view all the answers

    What metabolic effect is seen in muscle due to deficiencies in glycolytic enzymes like pyruvate kinase?

    <p>Fatigue and reduced energy production.</p> Signup and view all the answers

    How does lactic acidosis differ between Type A and Type B conditions?

    <p>Type B is associated with poor tissue oxygenation.</p> Signup and view all the answers

    What is a consequence of the high protein synthesis in the liver during cancer cachexia?

    <p>Augmented lactate production from muscle glycolysis.</p> Signup and view all the answers

    What is the primary role of lactate produced during anaerobic glycolysis?

    <p>It helps to replenish NAD to allow glycolysis to continue.</p> Signup and view all the answers

    Match the following biochemical concepts with their descriptions:

    <p>Glycolysis = The main pathway of glucose utilization Substrate-level phosphorylation = Direct donation of phosphate to ADP from an intermediate Triose phosphate = A C3 compound involved in glycolysis NAD+ = A cofactor essential for glycolytic reactions</p> Signup and view all the answers

    Match the following glycolysis products with their corresponding balances in the reaction:

    <p>Glucose = Starting molecule for glycolysis Lactate = End product of anaerobic metabolism ATP = Energy currency generated during glycolysis H2O = Byproduct of glycolysis</p> Signup and view all the answers

    Match the following molecules with their roles in glycolysis:

    <p>ADP = Acceptor for phosphate to form ATP NADH = Reduced form of a cofactor generated in glycolysis Hexose phosphates = Phosphorylated form of monosaccharides in glycolysis Glycogen = Storage form of glucose, not directly involved in glycolysis</p> Signup and view all the answers

    Match the following glycolysis components with their biochemical forms:

    <p>Glucose-6-phosphate = Phosphorylated hexose involved in glycolysis Fructose-1,6-bisphosphate = An intermediate in the glycolytic pathway Pyruvate = The end product of glycolysis before entering the citric acid cycle Acetyl-CoA = Product formed from pyruvate after glycolysis</p> Signup and view all the answers

    Match the following enzymatic processes with their respective roles:

    <p>Phosphorylation of glucose = Conversion of glucose to glucose-6-phosphate Reduction of NAD+ = Transformation to NADH during glycolysis ATP production = Generated through substrate-level phosphorylation Oxidation of triose phosphate = Conversion to pyruvate in the glycolytic pathway</p> Signup and view all the answers

    Match the following glycolytic intermediates with their corresponding roles:

    <p>Glucose-6-phosphate = Irreversible phosphorylation of glucose Pyruvate = Final product of glycolysis Lactate = Produced under anaerobic conditions ADP = Substrate limiting ATP generation</p> Signup and view all the answers

    Match the following enzymes with their key functions in glycolysis:

    <p>Hexokinase = Catalyzes the conversion of glucose to glucose-6-phosphate Pyruvate kinase = Converts phosphoenolpyruvate to pyruvate Lactate dehydrogenase = Reduces pyruvate to lactate Phosphofructokinase = Regulates the commitment step of glycolysis</p> Signup and view all the answers

    Match the following metabolic conditions with their effects on glycolysis:

    <p>Anaerobic conditions = Block glycolysis at specific steps High ADP levels = Stimulates glycolytic pathway activation High glucose-6-phosphate = Inhibits hexokinase activity Presence of mitochondria = Facilitates oxidative phosphorylation</p> Signup and view all the answers

    Match the following substrates/products with their implications in glycolysis:

    <p>Glucose = Starting substrate for glycolysis NADH = Generated during glyceraldehyde-3-phosphate conversion ATP = Energy currency produced in glycolysis CO2 = A byproduct in aerobic metabolism</p> Signup and view all the answers

    Match the following key glycolytic processes with their descriptions:

    <p>Substrate-level phosphorylation = Direct ATP synthesis from ADP Facilitated transport = Glucose entry into cells Allosteric regulation = Control of enzyme activity by metabolites Irreversible steps = Key regulatory points in metabolic pathways</p> Signup and view all the answers

    Study Notes

    Glycolysis

    • A major pathway for glucose and other carbohydrate metabolism in cells
    • Occurs in the cytosol of cells
    • Functions aerobically or anaerobically
    • Provides ATP in the absence of oxygen, allowing tissues to survive anoxic episodes.
    • The main substrate is glucose but other carbohydrates can be used
    • The pathway is divided into two phases
      • The first stage uses ATP to phosphorylate glucose and convert it to glyceraldehyde 3-phosphate
      • The second phase generates ATP and NADH by oxidizing glyceraldehyde 3-phosphate to pyruvate.

    Pyruvate Dehydrogenase Complex

    • A multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA
    • The reaction is irreversible in mammals and is the gateway to the citric acid cycle
    • The complex is composed of three enzymes
    • Pyruvate decarboxylase
    • Dihydrolipoyl transacetylase
    • Dihydrolipoyl dehydrogenase
    • Contains five coenzymes
    • Thiamine pyrophosphate (TPP)
    • Lipoic acid
    • CoA
    • FAD
    • NAD+
    • The complex is regulated via covalent modification by phosphorylation and dephosphorylation

    Regulation Of Pyruvate Dehydrogenase

    • Inhibited by its products, acetyl-CoA and NADH.
    • Actively regulated by covalent modifications; phosphorylation decreases activity, dephosphorylation increases activity

    Anaerobic Glycolysis and Lactic Acidosis

    • Important in muscle function; provides ATP in the absence of oxygen
    • Lactate is produced when pyruvate is reduced in the absence of oxygen
    • Lactic acidosis caused by two main types
      • Type A results from impaired tissue perfusion or hypoxia
      • Type B results from impaired ability to metabolize lactate
    • Thiamin deficiency impairs the activity of pyruvate dehydrogenase, preventing pyruvate oxidation and leading to lactic acidosis

    Regulation of Glycolysis

    • Regulation of glycolysis occurs at three steps catalyzed by irreversible reactions
      • Hexokinase
      • Phosphofructokinase-1 (PFK-1)
      • Pyruvate kinase
    • PFK-1 is the main regulatory enzyme in glycolysis.

    The 2,3-bisphosphoglycerate Pathway in Erythrocytes

    • Provides 2,3-bisphosphoglycerate, which decreases the affinity of hemoglobin for O2 and increases oxygen delivery to the tissues.
    • This pathway does not produce net ATP, but it allows for efficient O2 delivery to the tissues.

    Fructose Metabolism

    • Fructose enters glycolysis by phosphorylation to fructose-1-phosphate, bypassing the main regulatory steps.
    • This results in the formation of more pyruvate and acetyl-CoA than is needed for ATP formation.
    • Increases in fructose-1-phosphate activate glucokinase, increasing hepatic glucose uptake and predisposing to hepatic steatosis

    Heart Muscle & Glycolysis

    • Heart muscle is specialized for aerobic performance.
    • It has low glycolytic activity and struggles to survive under ischemic conditions.

    Glycolysis & Cancer Cells

    • Fast-growing cancer cells have high glycolytic rates.
    • They produce large amounts of pyruvate, which is reduced to lactate and released.
    • This lactate fuels gluconeogenesis in the liver.
    • This cycle contributes to hypermetabolism, which can lead to cachexia.

    Lactic Acidosis

    • Lactic acidosis is characterized by an accumulation of lactate in the blood. It can occur in two types:
      • Type A: Occurs during situations of reduced tissue oxygenation (hypoxia).
      • Type B: Occurs due to metabolic disorders affecting lactate production or utilization.

    Ethanol Formation in Microorganisms

    • Some microorganisms, like yeast, convert pyruvate to ethanol under anaerobic conditions.

    Glycogen vs. Glucose

    • Using glycogen instead of glucose for anaerobic glycolysis in muscle is more efficient.
    • Glycogen phosphorylase produces glucose-1-phosphate.
    • Glucose-1-phosphate is interconverted with glucose-6-phosphate, saving the ATP that would be used by hexokinase.
    • This increases the net ATP yield from 2 to 3 per glucose molecule.

    Regulation of Glycolysis

    • Three irreversible reactions are key regulatory points:
      • Hexokinase (and glucokinase)
      • Phosphofructokinase
      • Pyruvate kinase.
    • Phosphofructokinase is inhibited by high ATP levels but activated by 5'AMP, indicating a need for increased glycolysis.

    Pyruvate Dehydrogenase (PDH)

    • This multienzyme complex oxidizes pyruvate to acetyl-CoA. It requires thiamin diphosphate as a cofactor.
    • PDH is regulated by:
      • Allosteric inhibition by its products (acetyl-CoA, NADH, and ATP).
      • Interconversion of active and inactive forms.

    Thiamine Deficiency & Lactic Acidosis

    • A deficiency in thiamine can lead to pyruvate and lactic acidosis.
    • This occurs due to impaired pyruvate metabolism.

    Inherited Enzyme Deficiencies

    • Inherited deficiencies in various glycolytic enzymes can cause different diseases:
      • Pyruvate kinase deficiency in erythrocytes causes hemolytic anemia.
      • Muscle phosphofructokinase deficiency leads to low exercise capacity.

    Summary of Glycolisis

    • Glycolisis is the pathway for glucose metabolism in most mammalian cells.
    • It occurs in the cytosol.
    • It produces pyruvate or lactate.
    • It is regulated by glucose transport and three key enzymes: hexokinase, phosphofructokinase, and pyruvate kinase.
    • Pyruvate is oxidized to acetyl-CoA by PDH.
    • Conditions affecting pyruvate metabolism often lead to lactic acidosis.

    Glycolysis: Pathway of Glucose Utilization

    • Glycolysis is the main pathway of glucose utilization in all mammalian cells.
    • The overall equation for glycolysis is: Glucose + 2 ADP + 2 Pi → 2 Lactate + 2 ATP + 2 H2O
    • All glycolytic enzymes are located in the cytosol.
    • ATP is generated through substrate-level phosphorylation, where phosphate groups are directly transferred from intermediates to ADP.
    • Glucose enters glycolysis by being phosphorylated to glucose-6-phosphate, catalyzed by hexokinase.
    • Hexokinase is allosterically inhibited by its product, glucose-6-phosphate.
    • Key enzymes in glycolysis:
      • Hexokinase: Phosphorylates glucose to glucose-6-phosphate. Inhibited by glucose-6-phosphate.
      • Phosphofructokinase: Catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate - the committed step of glycolysis. This enzyme is regulated by ATP, AMP, and other factors.
      • Enolase: Catalyzes dehydration of 2-phosphoglycerate to phosphoenolpyruvate. Inhibited by fluoride.
      • Pyruvate kinase: Transfers phosphate from phosphoenolpyruvate to ADP, generating ATP. This reaction is essentially irreversible under physiological conditions.
    • Under anaerobic conditions: pyruvate is reduced to lactate by lactate dehydrogenase. This regenerates NAD+ required for glycolysis to continue.
    • Under aerobic conditions: pyruvate is transported into mitochondria for oxidative decarboxylation to acetyl-CoA and further oxidation in the citric acid cycle.
    • Tissues that function under hypoxic conditions or have intrinsically high rates of glucose oxidation (eg, tumors, erythrocytes, retina, renal medulla) produce lactate.
    • The liver, kidneys, oxidative skeletal muscle, and heart can oxidize lactate under normal conditions, but can produce it under hypoxic conditions.
    • Under certain conditions, lactate can be transported directly into the mitochondria to generate pyruvate and NADH, contributing reducing equivalents to the electron transport chain.

    Glycolysis Regulation

    • Three irreversible reactions: catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase, are the major sites of regulation of glycolysis.
    • Phosphofructokinase: is significantly inhibited by ATP. 5' AMP, formed as ADP accumulates, can relieve this inhibition, signaling the need for increased glycolysis.

    Erythrocytes and Glycolysis

    • Erythrocytes lack mitochondria, so they rely on glycolysis for ATP production.
    • The initial phosphorylation step of glycolysis can be bypassed in erythrocytes, leading to the formation of 2,3-bisphosphoglycerate, which is important in decreasing the affinity of hemoglobin for O2.

    Pyruvate Oxidation

    • Pyruvate is oxidized to acetyl-CoA by pyruvate dehydrogenase complex, which requires thiamin diphosphate as a cofactor.
    • Conditions that impair pyruvate metabolism often lead to lactic acidosis.

    Inherited Metabolic Disorders

    • Pyruvate dehydrogenase deficiency: can lead to lactic acidosis and neurological disturbances.
    • Aldolase A deficiency and Pyruvate kinase deficiency in erythrocytes: cause hemolytic anemia.
    • Muscle phosphofructokinase deficiency: leads to low exercise capacity, especially on high-carbohydrate diets.

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