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13.1 - Introduction, Phosphorylation of Glucose

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  1. Front
    Carbohydrate metabolism
    Back
    How the body handles sugars
  2. Front
    Main sugar emphasized in carbohydrate metabolism
    Back
    Glucose
  3. Front
    Main question of this lecture section
    Back
    What happens to glucose after it enters a cell
  4. Front
    Two major pathways introduced at the start
    Back
    Glycolysis and the pentose phosphate pathway
  5. Front
    Core idea of carbohydrate metabolism section
    Back
    Glucose can be directed into different pathways depending on cellular needs
  6. Front
    Broad themes for carbohydrate study
    Back
    Structure and properties, digestion absorption and transport, metabolism by degradation and synthesis, regulation of metabolism, and diseases related to carbohydrate metabolism
  7. Front
    Structure and properties of carbohydrates
    Back
    What carbohydrates look like chemically and why they behave the way they do
  8. Front
    Digestion, absorption, and transport of carbohydrates
    Back
    How dietary carbohydrates are broken down, how glucose enters blood, and how glucose enters cells
  9. Front
    Carbohydrate degradation
    Back
    Breaking down glucose to make energy
  10. Front
    Carbohydrate synthesis
    Back
    Making or storing carbohydrate
  11. Front
    Regulation of carbohydrate metabolism
    Back
    How enzymes and hormones determine which pathway is active
  12. Front
    Diseases of carbohydrate metabolism
    Back
    Disorders that occur when carbohydrate pathways fail
  13. Front
    Main focus of this section
    Back
    Metabolism and regulation of carbohydrate pathways
  14. Front
    Glucose as a metabolic hub
    Back
    Glucose is a central molecule that can enter multiple metabolic pathways
  15. Front
    Dietary role in glucose metabolism
    Back
    Diet provides glucose as an input for metabolism
  16. Front
    Glycogenesis
    Back
    Conversion of glucose into glycogen for storage
  17. Front
    Glycogen
    Back
    Storage form of glucose
  18. Front
    Glycogenolysis
    Back
    Breakdown of glycogen back toward glucose intermediates
  19. Front
    Glycolysis
    Back
    Pathway that breaks down glucose for energy and eventually produces pyruvate
  20. Front
    End product of glycolysis
    Back
    Pyruvate
  21. Front
    Possible fate of pyruvate
    Back
    It can become lactate
  22. Front
    Another major fate of pyruvate
    Back
    It can become acetyl-CoA
  23. Front
    Role of acetyl-CoA in carbohydrate metabolism
    Back
    Acetyl-CoA enters the Krebs cycle
  24. Front
    Pentose phosphate pathway role in glucose metabolism
    Back
    Provides ribose phosphate for RNA and DNA synthesis
  25. Front
    Ribose phosphate
    Back
    Carbohydrate intermediate used to make RNA and DNA
  26. Front
    Relation of glucose to lipid synthesis
    Back
    Glycolytic intermediates and acetyl-CoA can feed fat-related pathways
  27. Front
    Most important idea from the glucose map
    Back
    Glucose has multiple possible metabolic fates
  28. Front
    Role of glucose in most cells
    Back
    Major energy source for most cells
  29. Front
    Glucose as a precursor
    Back
    Starting material for multiple biosynthetic pathways
  30. Front
    Phosphorylation
    Back
    Addition of a phosphate group to a molecule
  31. Front
    First major intracellular modification of glucose
    Back
    Phosphorylation to glucose-6-phosphate
  32. Front
    Glucose-6-phosphate (G6P)
    Back
    Phosphorylated form of glucose that is trapped inside the cell and enters multiple pathways
  33. Front
    Why phosphorylation traps glucose in the cell
    Back
    G6P is not recognized by glucose transporters and cannot diffuse across the membrane
  34. Front
    Metabolic trapping
    Back
    Retention of glucose inside the cell after conversion to G6P
  35. Front
    Why phosphorylation prepares glucose for metabolism
    Back
    G6P can enter glycolysis, the pentose phosphate pathway, glycogen synthesis, and other biosynthetic routes
  36. Front
    Biosynthetic products for which glucose can serve as precursor
    Back
    Fatty acids, cholesterol, amino acids, and nucleotides
  37. Front
    Key takeaway of glucose phosphorylation
    Back
    Phosphorylation keeps glucose in the cell and commits it to metabolism
  38. Front
    Reaction forming G6P
    Back
    Glucose + ATP → glucose-6-phosphate + ADP
  39. Front
    Source of phosphate in glucose phosphorylation
    Back
    ATP donates the phosphate group
  40. Front
    Energy cost of glucose phosphorylation
    Back
    The reaction uses ATP
  41. Front
    Enzymes that phosphorylate glucose
    Back
    Hexokinase and glucokinase
  42. Front
    Hexokinase tissue distribution
    Back
    Present in many tissues
  43. Front
    Glucokinase tissue distribution
    Back
    Present in the liver
  44. Front
    Central role of G6P
    Back
    G6P is a branch-point intermediate in glucose metabolism
  45. Front
    Glycolysis from G6P
    Back
    Uses G6P for energy production in all tissues
  46. Front
    Pentose phosphate pathway from G6P
    Back
    Uses G6P for NADPH and ribose production in all tissues
  47. Front
    Glycogen synthesis from G6P
    Back
    Uses G6P for glucose storage mainly in liver and muscle
  48. Front
    Other biosynthetic uses of G6P
    Back
    G6P contributes to glucuronides, glycans, and other compounds
  49. Front
    Connections of G6P
    Back
    G6P links with glycogenolysis and gluconeogenesis
  50. Front
    Tissues associated with glycolysis from G6P
    Back
    All tissues
  51. Front
    Tissues associated with pentose phosphate pathway from G6P
    Back
    All tissues
  52. Front
    Tissues associated with glycogen synthesis from G6P
    Back
    Mainly liver and muscle
  53. Front
    High-yield statement about G6P
    Back
    Glucose-6-phosphate is the key branching intermediate of glucose metabolism
  54. Front
    Isoenzymes
    Back
    Different forms of an enzyme that catalyze the same reaction but have different properties
  55. Front
    Shared reaction of hexokinase and glucokinase
    Back
    Both convert glucose to glucose-6-phosphate
  56. Front
    Hexokinases I–III
    Back
    Hexokinase isoenzymes found in various tissues
  57. Front
    Hexokinase I–III glucose affinity
    Back
    Low Km for glucose
  58. Front
    Meaning of low Km
    Back
    Enzyme works well at low substrate concentration and has high affinity
  59. Front
    Functional meaning of low Km hexokinase
    Back
    Hexokinase can phosphorylate glucose efficiently even when glucose concentration is low
  60. Front
    Product inhibition of hexokinase
    Back
    Hexokinase is inhibited by glucose-6-phosphate
  61. Front
    Meaning of product inhibition by G6P
    Back
    If G6P accumulates, hexokinase activity decreases
  62. Front
    Purpose of hexokinase product inhibition
    Back
    Prevents unnecessary trapping of more glucose when the cell already has excess G6P
  63. Front
    Functional goal of hexokinase
    Back
    Allows tissues to use glucose as an energy source even when glucose concentration is low
  64. Front
    Glucokinase
    Back
    Hexokinase IV
  65. Front
    Glucokinase locations
    Back
    Liver and pancreatic beta cells
  66. Front
    Glucokinase glucose affinity
    Back
    High Km for glucose
  67. Front
    Meaning of high Km
    Back
    Enzyme works better at higher substrate concentration and has lower affinity
  68. Front
    Functional meaning of high Km glucokinase
    Back
    Glucokinase becomes more active when glucose concentration is high
  69. Front
    Comparison at low glucose
    Back
    Hexokinase remains active while glucokinase is less active
  70. Front
    Comparison at high glucose
    Back
    Glucokinase activity rises more as glucose concentration increases
  71. Front
    Product inhibition of glucokinase
    Back
    Glucokinase is not inhibited by glucose-6-phosphate
  72. Front
    Why lack of G6P inhibition matters in liver
    Back
    Liver can continue phosphorylating glucose when glucose is abundant after a meal
  73. Front
    Insulin dependence of liver glucokinase synthesis
    Back
    Insulin stimulates glucokinase synthesis in the liver
  74. Front
    Role of liver glucokinase
    Back
    Handles and stores excess glucose
  75. Front
    Role of glucokinase in pancreatic beta cells
    Back
    Functions as a glucose sensor
  76. Front
    Hexokinase summary
    Back
    Most tissues, low Km, active at low glucose, inhibited by G6P, ensures glucose use
  77. Front
    Glucokinase summary
    Back
    Liver and beta cells, high Km, more active at high glucose, not inhibited by G6P, handles excess glucose and senses glucose
  78. Front
    Graph of hexokinase activity versus glucose concentration
    Back
    Hexokinase activity rises quickly at low glucose concentration
  79. Front
    Graph of glucokinase activity versus glucose concentration
    Back
    Glucokinase activity increases more gradually and becomes stronger at higher glucose concentration
  80. Front
    Physiologic meaning after a meal
    Back
    Increased blood glucose activates liver glucokinase so the liver can take up and process extra glucose
  81. Front
    Physiologic meaning during low glucose
    Back
    Tissues with hexokinase can still trap glucose efficiently
  82. Front
    Memory description of hexokinase
    Back
    Household enzyme that works steadily and well at low glucose
  83. Front
    Memory description of glucokinase
    Back
    Glucose overflow handler that is especially useful when glucose is high
  84. Front
    Glucokinase translocation
    Back
    Movement of glucokinase between the cytoplasm and nucleus
  85. Front
    Translocation
    Back
    Movement of a protein from one cellular location to another
  86. Front
    Why glucokinase location matters
    Back
    In the cytoplasm glucokinase is active, while in the nucleus it is held inactive by a regulatory system
  87. Front
    GKRP
    Back
    Glucokinase regulatory protein
  88. Front
    Effect of glucose on glucokinase translocation
    Back
    Glucose promotes movement of glucokinase out of the nucleus into the cytoplasm
  89. Front
    Result of glucose-induced glucokinase translocation
    Back
    More active glucokinase is available to phosphorylate glucose
  90. Front
    Effect of fructose-6-phosphate on glucokinase translocation
    Back
    F6P promotes translocation of glucokinase to the nucleus
  91. Front
    Effect of F6P on glucokinase activity
    Back
    F6P decreases active cytoplasmic glucokinase
  92. Front
    Effect of fructose-1-phosphate on glucokinase translocation
    Back
    F1P inhibits translocation of glucokinase to the nucleus
  93. Front
    Effect of F1P on glucokinase activity
    Back
    F1P helps keep glucokinase in the cytoplasm and supports glucose phosphorylation
  94. Front
    Why fructose stimulates hepatic glucose metabolism
    Back
    F1P prevents glucokinase movement into the nucleus, keeping more glucokinase active in the cytoplasm
  95. Front
    Potential harms of excess fructose intake
    Back
    Can contribute to fatty liver, increased uric acid, and gout over time
  96. Front
    Complete oxidation of glucose
    Back
    Full breakdown of glucose to CO₂ and H₂O
  97. Front
    Pathway to complete oxidation of glucose
    Back
    Glycolysis followed by conversion of pyruvate to acetyl-CoA and further oxidation
  98. Front
    First stage of glucose oxidation
    Back
    Glycolysis converts glucose to pyruvate
  99. Front
    Second stage after glycolysis
    Back
    Pyruvate is converted to acetyl-CoA
  100. Front
    Metabolic importance of acetyl-CoA
    Back
    Major entry point shared by glucose, fatty acids, and some amino acids
  101. Front
    Other fuels converging on acetyl-CoA
    Back
    Fatty acids and amino acids
  102. Front
    Big-picture meaning of glycolysis
    Back
    Glycolysis is only the first stage of glucose oxidation
  103. Front
    Requirement for full energy extraction from glucose
    Back
    Pyruvate must be converted to acetyl-CoA and oxidized further
  104. Front
    Full logic of section 13.1 pages 1–9
    Back
    Glucose enters the cell, is phosphorylated to G6P, is trapped and directed into pathways, and can ultimately be oxidized through pyruvate and acetyl-CoA
  105. Front
    Main carbohydrate fuel
    Back
    Glucose
  106. Front
    First key step of intracellular glucose metabolism
    Back
    Glucose is phosphorylated to glucose-6-phosphate
  107. Front
    General enzymes for first glucose phosphorylation
    Back
    Hexokinase in most tissues and glucokinase in liver and pancreatic beta cells
  108. Front
    Consequence of G6P formation
    Back
    G6P cannot leave through glucose transporters
  109. Front
    Major pathways branching from G6P
    Back
    Glycolysis, pentose phosphate pathway, glycogen synthesis, and other biosynthetic pathways
  110. Front
    Overall oxidative flow of glucose
    Back
    Glucose → G6P → glycolysis → pyruvate → acetyl-CoA → complete oxidation to CO₂ and H₂O

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