Glucose Metabolism and Transport Quiz
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Glucose Metabolism and Transport Quiz

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Questions and Answers

What is a major reason for the importance of glucose metabolism in the body?

  • Glucose can be directly converted to fats without processing.
  • It is the only source of energy for all cells.
  • Some tissues can only use glucose as a metabolic fuel. (correct)
  • Glucose metabolism primarily occurs in the liver only.

    • Which of the following correctly describes the role of transport proteins in glucose uptake?

  • They are only needed for glucose entry in muscle cells.
  • They create energy to actively pump glucose into cells.
  • They allow passive diffusion of glucose across membranes.
  • They are responsible for the facilitated movement of glucose due to its polarity. (correct)

    • During glycolysis and the TCA cycle, at which steps is chemical energy captured?

  • At multiple steps throughout glycolysis and TCA cycle. (correct)
  • Only in the TCA cycle, glycolysis does not capture energy.
  • Chemical energy is not captured at any step.
  • Only at the final step of glycolysis.

    • What is the significance of the pyruvate dehydrogenase complex?

    <p>It facilitates the conversion of pyruvate into acetyl-CoA.</p> Signup and view all the answers

    How does the body maintain glucose levels in circulation?

    <p>Through hormonal regulation and energy metabolism.</p> Signup and view all the answers

    What is the primary mechanism by which GLUT proteins facilitate glucose transport?

    <p>Facilitated diffusion</p> Signup and view all the answers

    Which GLUT transporter is primarily involved in insulin-regulated glucose storage?

    <p>GLUT4</p> Signup and view all the answers

    Where are cotransporters predominantly expressed?

    <p>Epithelial cells of the intestine and kidney</p> Signup and view all the answers

    Which GLUT protein is characterized as a high-affinity transporter and is found in neurons?

    <p>GLUT3</p> Signup and view all the answers

    What is the main function of GLUT2 in terms of glucose uptake?

    <p>Post-prandial uptake and glucose sensing</p> Signup and view all the answers

    Which enzyme is part of the Pyruvate Dehydrogenase Complex responsible for decarboxylation?

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

    What effect does Acetyl-CoA have on Pyruvate Dehydrogenase?

    <p>It allosterically inhibits the enzyme</p> Signup and view all the answers

    What is the result of a deficiency in Pyruvate Dehydrogenase?

    <p>Conversion of Pyruvate to Lactic acid</p> Signup and view all the answers

    Which cofactor is essential for the functioning of Pyruvate Dehydrogenase?

    <p>Lipoic acid</p> Signup and view all the answers

    What phenomenon occurs due to arsenic poisoning in relation to Pyruvate Dehydrogenase?

    <p>Inhibition of enzymes utilizing lipoic acid</p> Signup and view all the answers

    What is the primary role of coenzymes in relation to vitamins?

    <p>To assist in the synthesis of other biomolecules</p> Signup and view all the answers

    Which vitamin deficiency impacts the function of pyruvate dehydrogenase?

    <p>Pantothenic acid (B5)</p> Signup and view all the answers

    What levels are likely to increase due to vitamin deficiencies affecting pyruvate dehydrogenase?

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

    Where does the Tricarboxylic Acid (TCA) cycle primarily occur?

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

    Which enzyme catalyzes the reaction converting citrate to isocitrate in the TCA cycle?

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

    What is a key regulatory mechanism for isocitrate dehydrogenase activity?

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

    Which coenzyme is NOT involved in the α-ketoglutarate dehydrogenase complex?

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

    What is the primary function of the TCA cycle?

    <p>Produce metabolic intermediates</p> Signup and view all the answers

    What is produced when succinyl CoA is converted to succinate?

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

    Which enzyme is involved in the conversion of succinate to fumarate?

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

    Which compound enters the TCA cycle, bringing two carbons?

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

    What is the total theoretical yield of ATP from one molecule of Acetyl CoA in the TCA cycle?

    <p>12</p> Signup and view all the answers

    Which of the following regulates the activity of citrate synthase in the TCA cycle?

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

    Which of the following is produced during the oxidation of malate to oxaloacetate?

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

    What is the role of the electrons transferred from the TCA cycle to NADH and FADH2?

    <p>They generate ATP through oxidative phosphorylation.</p> Signup and view all the answers

    Which pair of molecules is produced as a byproduct when fumarate is converted to malate?

    <p>None, it's a reversible reaction</p> Signup and view all the answers

    What role does glucose play in specific tissues like the brain and erythrocytes?

    <p>It is the only metabolic fuel source for these tissues.</p> Signup and view all the answers

    What is a significant regulation mechanism concerning glycolysis and the TCA cycle?

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

    How is chemical energy captured during glycolysis?

    <p>Primarily through substrate-level phosphorylation.</p> Signup and view all the answers

    What defines the energy yield from glucose catabolism under anaerobic conditions?

    <p>The yield is significantly lower than aerobic conditions.</p> Signup and view all the answers

    Which transport mechanism facilitates glucose movement into cells?

    <p>Facilitated diffusion through transport proteins.</p> Signup and view all the answers

    What role does fructose-2,6-bisphosphate play in glycolysis?

    <p>Inhibits gluconeogenesis</p> Signup and view all the answers

    Which statement best describes the regulation of pyruvate kinase?

    <p>Activated by fructose-1,6-bisphosphate</p> Signup and view all the answers

    Which enzyme has a low affinity for glucose and is primarily found in the liver?

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

    What is the effect of high levels of ATP on phosphofructokinase activity?

    <p>Inhibits phosphofructokinase activity</p> Signup and view all the answers

    What is a characteristic of hexokinase regarding glucose concentration?

    <p>Low Km for glucose</p> Signup and view all the answers

    How is glucokinase's activity regulated by hormonal signals?

    <p>Activated by insulin</p> Signup and view all the answers

    What happens to fructose-1,6-bisphosphate in response to low ATP levels?

    <p>Activates phosphofructokinase</p> Signup and view all the answers

    What is produced directly during the conversion of succinyl CoA to succinate?

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

    Which type of regulation does pyruvate dehydrogenase primarily use?

    <p>Feedforward regulation</p> Signup and view all the answers

    Which enzyme is responsible for converting fumarate to malate?

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

    What is the total yield of ATP theoretical yield from one molecule of acetyl CoA in the TCA cycle?

    <p>12</p> Signup and view all the answers

    Which compound is formed from the oxidation of malate to oxaloacetate?

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

    Which of the following both activates and inhibits the citrate synthase enzyme in the TCA cycle?

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

    Which of the following is NOT a primary product generated directly from the TCA cycle?

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

    Which coenzyme is required for the function of succinate dehydrogenase?

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

    Which of the following statements best describes a primary role of FADH2 produced in the TCA cycle?

    <p>Enters the electron transport chain</p> Signup and view all the answers

    What is the primary function of hexokinase in glycolysis?

    <p>To phosphorylate glucose and trap it in the cell</p> Signup and view all the answers

    Which characteristic of glucokinase distinguishes it from hexokinase?

    <p>Operates efficiently at high glucose concentrations</p> Signup and view all the answers

    What is the product of the conversion of glucose-6-phosphate in the early stages of glycolysis?

    <p>Fructose-1,6-bisphosphate</p> Signup and view all the answers

    Which enzyme acts as a regulatory valve in glycolysis by catalyzing an irreversible reaction?

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

    What is one of the alternative fates of pyruvate after glycolysis?

    <p>Conversion to acetyl-CoA for the TCA cycle</p> Signup and view all the answers

    What indicates that hexokinase has a low Km and why is this significant?

    <p>It ensures glucose uptake occurs even at low concentrations</p> Signup and view all the answers

    Which step in glycolysis involves the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate?

    <p>Substrate-level phosphorylation</p> Signup and view all the answers

    What role does triose phosphate isomerase play in glycolysis?

    <p>Conversion of DHAP to Glyceraldehyde-3-P</p> Signup and view all the answers

    What is the primary function of coenzymes in relation to vitamin metabolism?

    <p>They facilitate the chemical reactions in which vitamins are involved.</p> Signup and view all the answers

    Which vitamin is essential for the synthesis of coenzyme A?

    <p>Pantothenic acid (B5)</p> Signup and view all the answers

    What symptom is commonly associated with a deficiency in vitamins affecting pyruvate dehydrogenase function?

    <p>Severe lethargy and fatigue</p> Signup and view all the answers

    Which of the following is NOT a symptom of vitamin deficiencies affecting pyruvate dehydrogenase function?

    <p>Improved cardiovascular function</p> Signup and view all the answers

    What is a consequence of impaired pyruvate dehydrogenase function due to vitamin deficiencies?

    <p>Decrease in energy production</p> Signup and view all the answers

    What triggers the activation of isocitrate dehydrogenase in the TCA cycle?

    <p>Ca2+ and ADP</p> Signup and view all the answers

    Which of the following enzymes is crucial for converting α-ketoglutarate to succinyl CoA in the TCA cycle?

    <p>α-ketoglutarate dehydrogenase complex</p> Signup and view all the answers

    Where does the TCA cycle primarily occur within the cell?

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

    Which tissue is primarily dependent on glucose as its sole metabolic fuel?

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

    What is the primary role of the transport proteins in glucose uptake?

    <p>To facilitate glucose movement across membranes</p> Signup and view all the answers

    What is the expected energy yield from glucose catabolism under anaerobic conditions?

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

    At which of the following steps is chemical energy first captured in glycolysis?

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

    Which of the following statements regarding the regulation of the TCA cycle is correct?

    <p>It is primarily regulated by feedback mechanisms involving citrate and ATP.</p> Signup and view all the answers

    What distinguishes facilitated diffusion from secondary active transport in the context of glucose uptake?

    <p>Facilitated diffusion is independent of sodium ions, while secondary active transport is not.</p> Signup and view all the answers

    Which GLUT transporter is specifically responsible for insulin-regulated glucose uptake in muscle and adipose tissues?

    <p>GLUT4</p> Signup and view all the answers

    Which of the following characteristics does NOT apply to the GLUT transporters?

    <p>They are all expressed on most cells in the body.</p> Signup and view all the answers

    What type of transport mechanism do sodium-glucose symporters utilize?

    <p>Secondary active transport</p> Signup and view all the answers

    Which statement accurately describes the functionality of GLUT2 transporter?

    <p>It mediates glucose uptake primarily in the renal and intestinal epithelial cells post-prandially.</p> Signup and view all the answers

    Which enzyme activity is NOT part of the Pyruvate Dehydrogenase Complex?

    <p>Lipoic acid synthase</p> Signup and view all the answers

    What disease results from a deficiency in Pyruvate Dehydrogenase?

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

    Which substance is a known inhibitor of Pyruvate Dehydrogenase due to arsenic poisoning?

    <p>Lipoic acid</p> Signup and view all the answers

    Which of the following statements regarding the reaction catalyzed by Pyruvate Dehydrogenase is true?

    <p>It is strictly regulated by both NADH and Acetyl-CoA.</p> Signup and view all the answers

    What is a clinical manifestation of Pyruvate Dehydrogenase deficiency?

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

    Which compound is formed during the conversion of malate to oxaloacetate?

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

    What is the direct yield of ATP from one molecule of acetyl CoA in the TCA cycle?

    <p>12</p> Signup and view all the answers

    Which enzyme is responsible for converting fumarate to malate in the TCA cycle?

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

    Which of the following compounds directly enters the electron transport chain after being produced in the TCA cycle?

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

    Which TCA cycle enzyme is regulated by both ATP and ADP?

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

    What is the primary function of hexokinase in glycolysis?

    <p>Catalyzes the phosphorylation of glucose</p> Signup and view all the answers

    Which of the following is NOT an activator of succinate dehydrogenase?

    <p>NAD+</p> Signup and view all the answers

    Which statement best characterizes glucokinase compared to hexokinase?

    <p>It has a higher Km and Vmax than hexokinase.</p> Signup and view all the answers

    What type of phosphorylation occurs during the conversion of succinyl CoA to succinate?

    <p>Substrate-level phosphorylation</p> Signup and view all the answers

    What role does pyruvate play in metabolism?

    <p>It can either enter the TCA cycle or be converted to lactate.</p> Signup and view all the answers

    Which of the following correctly describes the overall yield from the TCA cycle in terms of electron pairs transferred?

    <p>3 NADH and 1 FADH2</p> Signup and view all the answers

    At which steps in glycolysis do irreversible reactions occur?

    <p>Hexokinase, phosphofructokinase, and pyruvate kinase.</p> Signup and view all the answers

    What is the end product of the reaction catalyzed by pyruvate kinase?

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

    Which pathway can pyruvate not enter directly?

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

    Which of the following processes occurs during glycolysis?

    <p>Phosphorylation of ADP to ATP via substrate-level phosphorylation</p> Signup and view all the answers

    Which enzyme is responsible for the reaction that converts glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate?

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

    Study Notes

    Glucose Metabolism Importance

    • Glucose and related sugars are core components of the diet
    • Brain, erythrocytes, renal medulla, cornea, testes, and exercising muscles rely solely on glucose as fuel
    • Maintaining stable glucose levels in circulation is critical for the body (4.5 - 5.6 mmol/L fasting)

    Glucose Entry into Cells

    • Glucose is polar and requires transport proteins for membrane passage
    • There are two classes of transport proteins:
      • Facilitated diffusion: ATP independent, GLUT 1-4, expressed in most cells.
      • Cotransporters: Secondary active transport expressed in intestinal and kidney epithelial cells.

    Glucose Transporters

    • GLUT1: All cells, especially RBCs and brain, basal uptake.
    • GLUT2: Renal tubular cells, intestinal epithelial cells, liver cells, pancreatic β cells, high capacity, low affinity, post-prandial uptake and sensing.
    • GLUT3: Neurons, high affinity.
    • GLUT4: Adipose tissues, striated muscle, regulated by insulin, responsible for insulin-regulated glucose storage.

    Glycolysis

    • The breakdown of glucose to pyruvate, a ten-step process occurring in the cytoplasm
    • Net production: 2 ATP, 2 NADH, and 2 pyruvate

    Pyruvate Dehydrogenase Complex

    • Converts pyruvate to acetyl-CoA, an irreversible reaction, essential for the TCA cycle.
    • Located in the mitochondrial matrix.
    • Consists of three enzymes: pyruvate decarboxylase, dihydrolipoyl transacetylase, dihydrolipoyl dehydrogenase.
    • Requires five coenzymes: thiamine pyrophosphate (TPP), lipoic acid, CoA, FAD, NAD+.

    Pyruvate Dehydrogenase Deficiency

    • An X-linked inherited metabolic disorder causing congenital lactic acidosis.
    • Symptoms include developmental defects (CNS), muscular spasticity, and early death.
    • No effective therapy exists.

    Arsenic Poisoning

    • Arsenic inhibits enzymes utilizing lipoic acid as a cofactor, including pyruvate dehydrogenase.
    • Symptoms are neurological disturbances and death.

    Vitamin Deficiencies

    • Coenzymes require vitamins for synthesis: CoA requires panthotenic acid (B5), NAD requires niacin (B3), FAD requires riboflavin (B2), and TPP requires thiamine (B1).
    • Deficiencies affect pyruvate dehydrogenase function.
    • Symptoms include elevated pyruvate, lactate, and alanine levels, severe lethargy, and fatigue.
    • Complications can affect cardiovascular, nervous, muscular, and gastrointestinal systems.

    Tricarboxylic Acid (TCA) Cycle

    • Located in the mitochondrial matrix.
    • Main functions: energy yield and metabolic intermediates production.
    • Reactions:
      • Citrate synthase: Acetyl-CoA + oxaloacetate → citrate
      • Aconitase: Citrate → isocitrate
      • Isocitrate dehydrogenase: Isocitrate → α-ketoglutarate + CO2 + NADH
      • α-ketoglutarate dehydrogenase complex: α-ketoglutarate → succinyl CoA + CO2 + NADH.
      • Succinate thiokinase: Succinyl CoA → succinate + GTP, substrate-level phosphorylation.
      • Succinate dehydrogenase: Succinate → fumarate + FADH2, part of the electron transport chain.
      • Fumarase: Fumarate → malate.
      • Malate dehydrogenase: Malate → oxaloacetate + NADH.

    TCA Cycle Energetics

    • Two carbons enter as Acetyl CoA, two leave as CO2.
    • One GTP is produced directly.
    • Four electron pairs generate 3 NADH and 1 FADH2, which contribute to ATP generation through oxidative phosphorylation.
    • Theoretical ATP yield per Acetyl CoA: 12 (9 from 3 NADH, 2 from 1 FADH2, 1 from GTP)

    TCA Cycle Regulation

    • Enzymes regulated by inhibitors and activators:
      • Citrate Synthase: Inhibited by ATP, NADH, succinyl CoA, activated by Ca2+, ADP.
      • Isocitrate Dehydrogenase: Inhibited by ATP, NADH, activated by ADP, Ca2+.
      • α-ketoglutarate Dehydrogenase Complex: Inhibited by ATP, NADH, GTP, succinyl CoA, activated by Ca2+.

    Glycolysis and Energy Production

    • Glycolysis has two stages:
      • Energy Investment: 2 ATP consumed
      • Energy Payoff: 4 ATP produced, resulting in a net gain of 2 ATP, 2 NADH, and 2 pyruvate.
    • Aerobic Conditions: Pyruvate enters the TCA cycle, yielding significantly more ATP.
    • Anaerobic Conditions: Pyruvate is converted to lactate.

    Overall Energy Yield

    • Under aerobic conditions, glucose catabolism generates approximately 32 ATP molecules (2 from glycolysis, 2 from pyruvate oxidation, 28 from oxidative phosphorylation).
    • Under anaerobic conditions, glucose catabolism generates only 2 ATP molecules (from glycolysis).

    Glycolysis

    • Glycolysis is the breakdown of glucose into pyruvate.
    • The process occurs in the cytoplasm.
    • It is a 10 step process with the following key reactions:
      • Glucose phosphorylation: Glucose is phosphorylated to glucose-6-phosphate by hexokinase or glucokinase
      • Fructose-6-phosphate phosphorylation: Fructose-6-phosphate is phosphorylated to fructose-1,6-bisphosphate by phosphofructokinase
      • Glyceraldehyde-3-phosphate oxidation: Glyceraldehyde-3-phosphate is oxidized to 1,3-bisphosphoglycerate by glyceraldehyde-3-phosphate dehydrogenase
      • Pyruvate conversion: Phosphoenolpyruvate is converted to pyruvate by pyruvate kinase.
    • There are three key regulatory enzymes to control glycolysis:
      • Hexokinase: Inhibited by glucose-6-P
      • Phosphofructokinase: Inhibited by ATP and Citrate, activated by AMP and fructose-2,6-bisphosphate
      • Pyruvate kinase: Activated by Fructose-1,6-bisphosphate. These enzymes act as "metabolic valves".
    • Overall yield of glycolysis
      • 2 ATP molecules are generated (net)
      • 2 NADH molecules are generated
      • 2 pyruvate molecules are generated
    • Alternative metabolic fates of pyruvate:
      • Conversion to Acetyl-CoA: The pyruvate dehydrogenase complex catalyses the conversion of pyruvate to acetyl-CoA. Acetyl-CoA can enter the TCA cycle or serve as a precursor for fatty acid synthesis.
      • Conversion to Oxaloacetate: Pyruvate carboxylase converts pyruvate to oxaloacetate. Oxaloacetate can enter the TCA cycle or serve as a precursor for gluconeogenesis.
      • Reduction to Ethanol: Pyruvate decarboxylase catalyses the conversion of pyruvate to ethanol.

    Pyruvate Dehydrogenase Complex

    • The pyruvate dehydrogenase complex is essential for the conversion of pyruvate to acetyl-CoA.
    • The complex is located in the mitochondrial matrix.
    • The complex requires several coenzymes including NAD+, FAD, thiamine pyrophosphate, and lipoic acid.
    • Vitamin deficiencies (B1, B2, B3, B5) can lead to impaired pyruvate dehydrogenase function. This can cause symptoms such as lethargy, fatigue, and complications affecting cardiovascular, nervous, muscular, and gastrointestinal systems.

    Tricarboxylic Acid (TCA) Cycle

    • The TCA cycle is the central hub of metabolism.
    • It takes place in the mitochondrial matrix.
    • The cycle is a series of eight reactions that oxidize acetyl-CoA to CO2, generating high-energy electron carriers NADH and FADH2, which are utilized for ATP production during oxidative phosphorylation.
    • Key reactions:
      • Acetyl-CoA enters the cycle, combining with oxaloacetate to form citrate.
      • Citrate is isomerized to isocitrate.
      • Isocitrate is decarboxylated and oxidized to α-ketoglutarate, generating NADH.
      • α-ketoglutarate is decarboxylated and oxidized to succinyl-CoA, generating NADH.
      • Succinyl-CoA is converted to succinate, generating GTP.
      • Succinate is oxidized to fumarate, generating FADH2.
      • Fumarate is hydrated to malate.
      • Malate is oxidized to oxaloacetate, generating NADH and completing the cycle.
    • Overall yield of TCA Cycle per Acetyl-CoA:
      • 3 NADH
      • 1 FADH2
      • 1 GTP
    • This corresponds to 12 ATP molecules generated through oxidative phosphorylation.
    • TCA cycle regulation:
      • Citrate synthase: Inhibited by ATP, NADH, and succinyl CoA
      • Isocitrate dehydrogenase: Inhibited by ATP and NADH
      • α-ketoglutarate dehydrogenase complex: Inhibited by ATP, NADH, GTP, and succinyl CoA

    Glucose metabolism

    • Glucose is a major component of the diet, and is the primary fuel source for the brain, erythrocytes, renal medulla, cornea, testes, and exercising muscle.
    • The body maintains a constant glucose levels in circulation (fasting 4.5 - 5.6 mmol/L)
    • Glucose is a polar molecule that requires transporter proteins to cross cell membranes.
    • Glucose transport proteins:
      • GLUT 1-4: Facilitate diffusion (ATP independent)
      • SGLT 1: Secondary active transport (Sodium-glucose symporter)

    Glucose uptake into cells

    • GLUT1: Found in all cells, especially red blood cells and brain. Responsible for basal uptake.
    • GLUT2: Found in renal tubular cells, intestinal epithelial cells, liver cells, and pancreatic beta cells. High capacity, low affinity enables post-prandial uptake and glucose sensing.
    • GLUT3: Found in neurons. High affinity for glucose.
    • GLUT4: Found in adipose tissues (sensing) and striated muscle (skeletal and cardiac). Regulated by insulin, responsible for insulin-regulated glucose storage.

    Glucose phosphorylation

    • Once inside the cell, glucose is phosphorylated to glucose-6-phosphate, trapping it inside the cell. This is because there are no cell membrane transporters for phosphorylated sugars.
    • Glucose phosphorylation is catalyzed by:
      • Hexokinase: Found in all cells
      • Glucokinase: Found in liver parenchymal cells and pancreatic islet cells.

    Hexokinase vs. Glucokinase

    • Hexokinase:
      • Low Km (high affinity for glucose, even at low concentrations)
      • Low Vmax (limited capacity)
    • Glucokinase:
      • High Km (only operates efficiently at high glucose concentrations)
      • High Vmax (high capacity, allowing it to handle post-prandial glucose surges)

    Glycolysis

    • Glycolysis consists of 10 enzymatic steps that break down glucose into two pyruvate molecules
    • The first phase is the preparatory phase, where glucose is phosphorylated and cleaved into two 3-carbon molecules.
    • The second phase is the payoff phase, where ATP production occurs by substrate-level phosphorylation.
    • Net yield of glycolysis: 2 ATP, 2 NADH

    Alternative metabolic fates of pyruvate

    • Conversion to Acetyl-CoA: This occurs through the pyruvate dehydrogenase complex, and facilitates entry into the TCA cycle or fatty acid synthesis.
    • Conversion to Oxaloacetate: This occurs via pyruvate carboxylase, and provides a precursor for gluconeogenesis and the TCA cycle.
    • Reduction to Ethanol: Occurs in yeast and some bacteria, not in humans

    Pyruvate dehydrogenase complex

    • A multi-enzyme complex that converts pyruvate to Acetyl-CoA.
    • Contains three distinct enzymes:
      • Pyruvate decarboxylase
      • Dihydrolipoyl transacetylase
      • Dihydrolipoyl dehydrogenase
    • Requires 5 coenzymes: TPP, Lipoate, FAD, NAD, CoA

    Regulation of glycolysis

    • Hexokinase: Inhibited by its product, glucose-6-phosphate.
    • Phospho-fructokinase: Key regulatory enzyme. Activated by AMP and ADP, inhibited by ATP and citrate.
    • Pyruvate kinase: Activated by fructose-1,6-bisphosphate, inhibited by ATP, alanine, and acetyl-CoA.

    Pyruvate dehydrogenase complex regulation

    • Inhibitors: Acetyl-CoA, NADH, ATP
    • Activators: ADP, pyruvate, Ca++

    Clinical implications of pyruvate dehydrogenase complex dysfunction

    • Pyruvate dehydrogenase deficiency: Inherited genetic defect leading to congenital lactic acidosis. Symptoms include developmental defects, muscular spasticity and early death. No effective treatment.
    • Arsenic poisoning: Arsenic inhibits enzymes that use lipoic acid (a coenzyme for pyruvate dehydrogenase). Symptoms include neurological disturbances and death.

    TCA Cycle (Krebs Cycle)

    • Series of 8 metabolic steps that oxidize acetyl-CoA to carbon dioxide.
    • Occurs in the mitochondrial matrix
    • Generates NADH and FADH2, which power oxidative phosphorylation (ATP production)
    • Yields: 3 NADH, 1 FADH2, 1 GTP per acetyl-CoA

    Regulation of the TCA cycle

    • Citrate synthase: Inhibited by ATP, NADH, succinyl CoA. Activated by ADP.
    • Isocitrate dehydrogenase: Inhibited by ATP and NADH. Activated by ADP, Ca++.
    • α-ketoglutarate dehydrogenase complex: Inhibited by succinyl CoA, NADH, ATP. Activated by Ca++, ADP, and GTP.

    Energy yield from glucose metabolism

    • Aerobic conditions: Glucose yields 30-32 ATP molecules per glucose. This is significantly higher than anaerobic glycolysis.
    • Anaerobic conditions: Glucose yields only 2 ATP molecules per glucose. This is due to the lack of oxygen for oxidative phosphorylation.

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