Biochem 11.2  Gluconeogenesis Overview
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Questions and Answers

What occurs during lactic acid fermentation in oxygen-poor tissue?

  • Lactate is reversibly reduced to pyruvate. (correct)
  • Oxaloacetate is produced from lactate.
  • Gluconeogenesis is initiated directly from lactate.
  • Pyruvate is oxidized to lactate.
  • Which molecule cannot serve as a precursor for gluconeogenesis?

  • Acetyl-CoA (correct)
  • Oxaloacetate
  • Lactate
  • Pyruvate
  • How can gluconeogenic substrates that are metabolized directly to oxaloacetate benefit the energy consumption during gluconeogenesis?

  • They increase the rate of lactate formation.
  • They reduce the need for ATP consumption. (correct)
  • They provide NADH directly to the pathway.
  • They eliminate the need for glucose.
  • What is the first step when oxaloacetate needs to enter the cytosol?

    <p>It is reduced to malate in the mitochondrial matrix.</p> Signup and view all the answers

    What role does the malate-aspartate shuttle play in gluconeogenesis?

    <p>It transports NADH from the mitochondria to the cytosol.</p> Signup and view all the answers

    What is the result of oxidizing lactate to pyruvate?

    <p>Production of cytosolic NADH directly.</p> Signup and view all the answers

    Which substrates can produce oxaloacetate either directly or through the citric acid cycle?

    <p>Mostly amino acids and odd-chain fatty acids.</p> Signup and view all the answers

    What happens to oxaloacetate after it is reduced to malate in the cytosol?

    <p>It is converted back into oxaloacetate.</p> Signup and view all the answers

    What is the net effect of a futile cycle involving pyruvate and phosphoenolpyruvate?

    <p>Convert ATP to ADP</p> Signup and view all the answers

    How many ATP equivalents are required to convert one pyruvate to phosphoenolpyruvate?

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

    Which enzyme catalyzes the conversion of 3-phosphoglycerate to 1,3-bisphosphoglycerate?

    <p>Phosphoglycerate kinase</p> Signup and view all the answers

    What occurs when one pyruvate molecule is converted into two G3P molecules?

    <p>Two NADH are consumed</p> Signup and view all the answers

    Which enzyme in glycolysis is responsible for synthesizing fructose 1,6-bisphosphate?

    <p>Phosphofructokinase-1</p> Signup and view all the answers

    What is the role of the enzyme fructose-1,6-bisphosphatase in gluconeogenesis?

    <p>Catalyze a hydrolysis reaction</p> Signup and view all the answers

    Which of the following statements is true regarding the regulation of glycolysis and gluconeogenesis?

    <p>Irreversible enzymes are tightly regulated to avoid energy waste.</p> Signup and view all the answers

    What happens to dihydroxyacetone phosphate (DHAP) in the gluconeogenesis pathway?

    <p>It combines with G3P to form fructose 1,6-bisphosphate.</p> Signup and view all the answers

    What is the primary role of insulin in relation to glycolysis?

    <p>It activates phosphoprotein phosphatase-1 (PP1).</p> Signup and view all the answers

    Which hormone is primarily involved in increasing blood glucose levels during fasting?

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

    How does F2,6BP affect PFK-1 in glycolysis?

    <p>It activates its activity.</p> Signup and view all the answers

    What is the effect of glucagon on PKA?

    <p>It activates PKA activity.</p> Signup and view all the answers

    During which physiological state is insulin released?

    <p>Fed state</p> Signup and view all the answers

    Which enzyme is specifically inhibited by insulin to prevent gluconeogenesis?

    <p>FBPase-1</p> Signup and view all the answers

    What is the main action of glucagon after binding to its receptor?

    <p>Activates cAMP-dependent protein kinase A (PKA).</p> Signup and view all the answers

    How does insulin affect glycolysis when energy levels are high?

    <p>It continues to stimulate glycolysis despite high ATP levels.</p> Signup and view all the answers

    What role does ATP play in the regulation of phosphofructokinase-1 (PFK-1)?

    <p>ATP inhibits PFK-1 activity</p> Signup and view all the answers

    Which of the following molecules is a potent allosteric stimulator of PFK-1 activity?

    <p>Fructose 2,6-bisphosphate</p> Signup and view all the answers

    What happens to PFK-1 activity when ATP levels drop?

    <p>PFK-1 activity is stimulated</p> Signup and view all the answers

    How does citrate affect PFK-1 activity?

    <p>Citrate inhibits PFK-1 activity</p> Signup and view all the answers

    What is the role of phosphofructokinase-2 (PFK-2) in glycolysis?

    <p>PFK-2 produces fructose 2,6-bisphosphate to regulate PFK-1.</p> Signup and view all the answers

    What is the relationship between ADP and PFK-1 activity?

    <p>ADP activates PFK-1 activity.</p> Signup and view all the answers

    Which enzyme is responsible for the degradation of fructose 2,6-bisphosphate?

    <p>FBPase-2</p> Signup and view all the answers

    Where does the citric acid cycle occur in the cell?

    <p>In the mitochondria</p> Signup and view all the answers

    What is one reason the liver uses ATP for gluconeogenesis despite the cost?

    <p>To ensure other tissues have a continuous supply of glucose</p> Signup and view all the answers

    Which enzyme in glycolysis is primarily inhibited by its product glucose 6-phosphate in most cells?

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

    How does the liver regulate glycolysis differently than other tissues?

    <p>Glucokinase in the liver is not inhibited by glucose 6-phosphate</p> Signup and view all the answers

    What happens to glycolytic flux when product levels are excessively high in tissues that do not perform gluconeogenesis?

    <p>Glycolytic flux decreases</p> Signup and view all the answers

    Which of the following is NOT an allosteric inhibitor of pyruvate kinase?

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

    What metabolic pathway primarily provides ATP for red blood cells?

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

    What is the role of feedback inhibition in glycolysis in tissues like muscle and red blood cells?

    <p>Slowing glycolysis when product levels are high</p> Signup and view all the answers

    Why is it important for the regulation of glycolysis to be tightly controlled in tissues that express gluconeogenesis enzymes?

    <p>To prevent unnecessary energy expenditure</p> Signup and view all the answers

    What role does fructose 2,6-bisphosphate (F2,6BP) play in muscle glycolysis?

    <p>It activates phosphofructokinase-1 (PFK-1).</p> Signup and view all the answers

    In muscle cells, what primarily regulates the levels of fructose 2,6-bisphosphate (F2,6BP)?

    <p>Substrate levels of fructose 6-phosphate.</p> Signup and view all the answers

    What is the primary effect of a sudden increase in glucose 6-phosphate levels in a muscle cell?

    <p>Accumulation of fructose 6-phosphate.</p> Signup and view all the answers

    Which enzyme is primarily affected by the accumulation of fructose 2,6-bisphosphate (F2,6BP) in muscle cells?

    <p>Phosphofructokinase-1 (PFK-1).</p> Signup and view all the answers

    What is the rationale for the feedback inhibition of hexokinase in glycolysis?

    <p>When glucose 6-phosphate levels are high.</p> Signup and view all the answers

    Which compound serves as a sign of low energy stores and activates phosphofructokinase-1 (PFK-1)?

    <p>Fructose 2,6-bisphosphate.</p> Signup and view all the answers

    How do liver cells differ from muscle cells in their regulation of glycolysis?

    <p>Liver cells experience hormonal control through covalent regulation.</p> Signup and view all the answers

    What happens to the PFK-1 activity when fructose 6-phosphate accumulates in muscle cells?

    <p>F2,6BP is produced, which activates PFK-1.</p> Signup and view all the answers

    Study Notes

    Gluconeogenesis Introduction

    • Gluconeogenesis is the process of building glucose from two pyruvate molecules
    • It requires more energy (2 NADH and 6 ATP) than glycolysis releases
    • This process is vital during fasting or for recycling glycolysis end products
    • Gluconeogenesis and glycolysis must be regulated to prevent energy loss

    Gluconeogenesis

    • Primarily takes place in the liver, although other cell types can also support it
    • This compartmentalization reflects the liver's role in providing fuel during fasting
    • Gluconeogenesis shares some enzymes with glycolysis, but is not simply glycolysis in reverse
    • Gluconeogenesis requires unique enzymes to bypass three irreversible steps in glycolysis
    • These bypass reactions are also irreversible and are catalyzed by different, unique enzymes

    Bypass Reactions in Gluconeogenesis

    • For each of the three irreversible steps of glycolysis, unique enzymes are used by gluconeogenesis
    • These bypass reactions are also irreversible and catalyzed by distinct, unique enzymes
    • The other seven reversible reactions of glycolysis are shared with gluconeogenesis

    The First Set of Bypass Reactions

    • Pyruvate is converted to oxaloacetate through pyruvate carboxylase
    • This reaction consumes one ATP molecule and occurs in the mitochondrial matrix
    • Oxaloacetate is then converted to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase (PEPCK)
    • This reaction consumes one GTP molecule and occurs either in the mitochondrial or cytosolic compartments

    Alternate Entry Points of Gluconeogenesis

    • Other molecules beyond pyruvate (like alanine and lactate) can contribute to gluconeogenesis
    • Alanine is converted to pyruvate through deamination
    • Lactate is reversibly reduced to pyruvate for gluconeogenesis
    • Some substrates are directly metabolized into oxaloacetate without first becoming pyruvate
    • Examples include many amino acids and odd-chain fatty acids
    • Acetyl-CoA does not serve as a precursor for gluconeogenesis

    The Cori Cycle

    • It's a pathway connecting glycolysis and gluconeogenesis
    • During strenuous exercise, muscles produce lactate, which is transported to the liver
    • In the liver, lactate is converted back to pyruvate and used in gluconeogenesis
    • The generated glucose is released to the bloodstream and can be used by muscles

    Regulation of Glucose Metabolism

    • Glycolysis and gluconeogenesis are regulated to maintain stable metabolite levels
    • Hexokinase, phosphofructokinase-1, and pyruvate kinase are regulated mainly in non-gluconeogenic tissues
    • Hexokinase is inhibited by its product (glucose-6-phosphate)
    • Pyruvate kinase is inhibited by its product (ATP) and by acetyl-CoA and long-chain fatty acids
    • Phosphofructokinase-1 (PFK-1) is the most regulated enzyme, inhibited by ATP and activated by ADP and AMP
    • The metabolite citrate also inhibits PFK-1
    • Fructose 2,6-bisphosphate (F2,6BP) is a potent activator of PFK-1
    • F2,6BP is generated by PFK-2 and degraded by FBPase-2
    • Covalent regulation (activation and deactivation by phosphorylation/dephosphorylation) also affects glycolysis regulation, especially in the liver
    • Insulin activates the enzyme phosphoprotein phosphatase-1 (PP1)
    • Glucagon and epinephrine activate protein kinase A (PKA) which leads to deactivating PFK-2 and activating FBPase-2
    • This complex regulation maintains blood glucose homeostasis

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    Gluconeogenesis PDF

    Description

    This quiz covers the essential concepts of gluconeogenesis, including its biochemical pathway and its critical role during fasting. Learn about the unique enzymes involved and how gluconeogenesis differs from glycolysis. Test your understanding of the regulation of these metabolic processes.

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