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13.4 - Regulation of Glycolysis

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  1. Front
    Regulation of glycolysis
    Back
    Glycolysis is controlled mainly through key regulatory enzymes and mechanisms
  2. Front
    Key allosteric glycolytic enzymes
    Back
    Hexokinase, phosphofructokinase-1, and pyruvate kinase
  3. Front
    Allosteric regulation
    Back
    Fast and easily reversible regulation of enzyme activity by small molecules binding outside the active site
  4. Front
    Mechanism of allosteric regulation
    Back
    A ligand binds to an allosteric site, changes enzyme conformation, and alters activity
  5. Front
    Common feature of allosteric inhibitors
    Back
    Often products of a reaction or pathway
  6. Front
    Main regulatory enzymes of glycolysis
    Back
    Hexokinase, PFK-1, and pyruvate kinase
  7. Front
    Most important regulatory enzyme of glycolysis
    Back
    PFK-1
  8. Front
    Opposite regulators of glycolysis
    Back
    ATP and AMP
  9. Front
    Effect of ATP on glycolysis
    Back
    Signals high energy and inhibits glycolysis
  10. Front
    Effect of AMP on glycolysis
    Back
    Signals low energy and activates glycolysis
  11. Front
    Adenylate kinase reaction
    Back
    ADP + ADP → ATP + AMP
  12. Front
    Role of adenylate kinase in muscle
    Back
    Generates AMP when ADP accumulates during energy use
  13. Front
    Effect of muscle activity on ATP and AMP
    Back
    ATP decreases and AMP increases during heavy activity
  14. Front
    Significance of AMP increase
    Back
    AMP signals energy demand and stimulates glycolysis
  15. Front
    Fructose-2,6-bisphosphate (F-2,6-BP)
    Back
    A key regulatory molecule in glycolysis
  16. Front
    Nature of F-2,6-BP
    Back
    Not an intermediate of glycolysis but a regulator
  17. Front
    Effect of F-2,6-BP on PFK-1
    Back
    Allosterically activates PFK-1
  18. Front
    Effect of F-2,6-BP on glycolysis
    Back
    Enhances glycolysis in liver
  19. Front
    Interaction of F-2,6-BP with ATP
    Back
    Can oppose the inhibitory effects of ATP on PFK-1
  20. Front
    Role of F-2,6-BP in liver metabolism
    Back
    Forces activation of glycolysis for fatty acid synthesis
  21. Front
    Enzyme that produces F-2,6-BP
    Back
    Phosphofructokinase-2 (PFK-2)
  22. Front
    Enzyme that converts F-2,6-BP to F6P
    Back
    Fructose-2,6-bisphosphatase (FBPase-2)
  23. Front
    Effect of F-2,6-BP on gluconeogenesis
    Back
    Inhibits fructose-1,6-bisphosphatase (FBPase-1)
  24. Front
    Overall effect of F-2,6-BP
    Back
    Promotes glycolysis and inhibits gluconeogenesis
  25. Front
    Regulation of F-2,6-BP levels
    Back
    Controlled by the insulin to glucagon ratio
  26. Front
    Covalent modification regulation
    Back
    Regulation of enzyme activity by phosphorylation and dephosphorylation
  27. Front
    Protein kinase
    Back
    Enzyme that adds phosphate groups to proteins
  28. Front
    Protein phosphatase
    Back
    Enzyme that removes phosphate groups from proteins
  29. Front
    Phosphorylation
    Back
    Addition of phosphate to amino acids such as serine, threonine, tyrosine, or histidine
  30. Front
    Effect of phosphorylation on metabolism
    Back
    Changes enzyme activity and regulates metabolic pathways
  31. Front
    Role of insulin/glucagon ratio
    Back
    Determines phosphorylation state and activity of metabolic enzymes
  32. Front
    General rule of phosphorylation
    Back
    Catabolic enzymes are activated by phosphorylation and anabolic enzymes are inhibited by phosphorylation
  33. Front
    General rule of dephosphorylation
    Back
    Catabolic enzymes are inhibited by dephosphorylation and anabolic enzymes are activated by dephosphorylation
  34. Front
    Coordination by protein kinases
    Back
    Protein kinases can regulate multiple pathways simultaneously through phosphorylation of many targets
  35. Front
    Protein kinase A (PKA)
    Back
    A major kinase controlling metabolism
  36. Front
    Activation of PKA
    Back
    Activated by glucagon and adrenaline
  37. Front
    Second messenger in PKA pathway
    Back
    cAMP
  38. Front
    Definition of second messenger
    Back
    An intracellular molecule that transmits signals from receptors to targets
  39. Front
    Effect of cAMP
    Back
    cAMP activates protein kinase A
  40. Front
    Action of PKA
    Back
    PKA phosphorylates target enzymes and alters their activity
  41. Front
    Target of PKA phosphorylation
    Back
    Serine residues on key regulatory enzymes
  42. Front
    Core signaling pathway
    Back
    Glucagon or adrenaline → cAMP → PKA → phosphorylation of metabolic enzymes
  43. Front
    Repeated concept of cAMP and PKA
    Back
    cAMP activates PKA, which phosphorylates metabolic enzymes
  44. Front
    Effect of insulin on glycolysis in liver
    Back
    Activates glycolysis
  45. Front
    Mechanism of insulin action
    Back
    Insulin activates protein phosphatase leading to dephosphorylation
  46. Front
    Effect of insulin on PFK-2
    Back
    Increases PFK-2 activity
  47. Front
    Result of increased PFK-2 activity
    Back
    Increases F-2,6-BP levels
  48. Front
    Final effect of insulin on glycolysis
    Back
    Increased F-2,6-BP activates PFK-1 and enhances glycolysis
  49. Front
    Regulation of pyruvate kinase
    Back
    Pyruvate kinase is regulated by covalent modification
  50. Front
    Regulators of hepatic pyruvate kinase
    Back
    Protein kinase A and protein phosphatase
  51. Front
    Specific regulation of pyruvate kinase
    Back
    Only the hepatic isoenzyme is regulated by covalent modification
  52. Front
    Effect of PKA on pyruvate kinase
    Back
    Phosphorylation modifies enzyme activity
  53. Front
    Effect of protein phosphatase on pyruvate kinase
    Back
    Dephosphorylation modifies enzyme activity
  54. Front
    Anabolic importance of glycolysis
    Back
    Glycolysis provides intermediates for biosynthesis
  55. Front
    Role of glycolysis in liver metabolism
    Back
    Supports anabolic processes such as fatty acid synthesis
  56. Front
    Effect of insulin in liver metabolism
    Back
    Promotes glycolysis and anabolic pathways
  57. Front
    Overall regulation flow of glycolysis
    Back
    Glycolysis is regulated by allosteric control, energy status, and hormonal signaling
  58. Front
    Summary of glycolysis regulation enzymes
    Back
    Hexokinase, PFK-1, and pyruvate kinase are the main control points
  59. Front
    Summary of PFK-1 regulation
    Back
    PFK-1 is the key control enzyme influenced by ATP, AMP, and F-2,6-BP
  60. Front
    Summary of AMP role
    Back
    AMP increases during energy demand and activates glycolysis
  61. Front
    Summary of F-2,6-BP role
    Back
    Activates glycolysis and inhibits gluconeogenesis in liver
  62. Front
    Summary of hormonal regulation
    Back
    Hormones regulate glycolysis via phosphorylation and dephosphorylation
  63. Front
    Summary of PKA pathway
    Back
    Glucagon or adrenaline activates cAMP, which activates PKA, leading to phosphorylation of enzymes
  64. Front
    Summary of insulin action
    Back
    Insulin activates protein phosphatase, increases PFK-2 activity, and promotes glycolysis
  65. Front
    Summary of hepatic pyruvate kinase regulation
    Back
    Liver pyruvate kinase is controlled by phosphorylation and dephosphorylation
  66. Front
    Overall purpose of glycolysis regulation
    Back
    Adjust glycolysis based on energy status and hormonal signals

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