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15.3 - Lipid stores as energy source: Ketone bodies

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  1. Front
    Fasting state hormonal pattern
    Back
    Low insulin and high glucagon and adrenaline
  2. Front
    Fasting state signaling pathway
    Back
    Increased cAMP leads to increased PKA activity
  3. Front
    Effect of fasting signaling on HSL
    Back
    Hormone-sensitive lipase is activated
  4. Front
    Effect of HSL activation in fasting
    Back
    Triacylglycerol is broken down to free fatty acids
  5. Front
    How free fatty acids travel in fasting
    Back
    They circulate in blood bound to albumin
  6. Front
    Main destination of free fatty acids in fasting
    Back
    Liver for beta-oxidation
  7. Front
    Immediate consequence of fasting-induced beta-oxidation in liver
    Back
    Large amounts of acetyl-CoA are produced
  8. Front
    Requirement for acetyl-CoA entry into the TCA cycle
    Back
    Sufficient oxaloacetate must be available
  9. Front
    Why oxaloacetate is low in fasting
    Back
    It is being used for gluconeogenesis
  10. Front
    Why acetyl-CoA accumulates in fasting
    Back
    Oxaloacetate is low, so acetyl-CoA cannot efficiently enter the TCA cycle
  11. Front
    What happens to excess acetyl-CoA in fasting
    Back
    It is converted into ketone bodies
  12. Front
    Why ketone bodies form
    Back
    They are produced when acetyl-CoA is high and TCA cycle entry is limited by low oxaloacetate
  13. Front
    Ketone bodies
    Back
    Backup fuel formed from excess acetyl-CoA when the TCA cycle is limited
  14. Front
    Ketogenesis
    Back
    Synthesis of ketone bodies from acetyl-CoA
  15. Front
    Location of ketogenesis
    Back
    Liver mitochondria
  16. Front
    Substrate for ketone body synthesis
    Back
    Acetyl-CoA
  17. Front
    Three ketone bodies
    Back
    Acetoacetate, beta-hydroxybutyrate, and acetone
  18. Front
    First key enzyme in ketogenesis
    Back
    Thiolase
  19. Front
    Rate-limiting or very important enzyme in ketogenesis
    Back
    HMG-CoA synthase
  20. Front
    Other key enzymes in ketogenesis
    Back
    HMG-CoA lyase and beta-hydroxybutyrate dehydrogenase
  21. Front
    Properties of ketone bodies
    Back
    Water-soluble, easily transported in blood, and used by many tissues
  22. Front
    Why ketone bodies solve a transport problem
    Back
    They are water-soluble and can travel in blood more easily than hydrophobic fatty acids
  23. Front
    Tissues that use ketone bodies
    Back
    Almost all tissues including muscle and brain
  24. Front
    Important tissue that can use ketone bodies
    Back
    Brain
  25. Front
    Tissues that cannot use ketone bodies
    Back
    Liver and red blood cells
  26. Front
    Why the liver cannot use ketone bodies
    Back
    It lacks SCOT, also called succinyl-CoA transferase
  27. Front
    Missing enzyme in liver ketone body utilization
    Back
    SCOT
  28. Front
    First step of ketone body utilization
    Back
    Ketone body is converted to acetoacetate
  29. Front
    Second step of ketone body utilization
    Back
    Acetoacetate is converted to acetoacetyl-CoA
  30. Front
    Third step of ketone body utilization
    Back
    Acetoacetyl-CoA is split into two acetyl-CoA
  31. Front
    Final fate of acetyl-CoA from ketone bodies
    Back
    It enters the TCA cycle to produce ATP
  32. Front
    Approximate ATP yield from acetoacetate
    Back
    About 19 ATP
  33. Front
    Main metabolic role of ketone bodies
    Back
    They are converted back to acetyl-CoA for ATP production
  34. Front
    When ketone bodies are produced
    Back
    Fasting, starvation, and diabetes
  35. Front
    Metabolic changes that promote ketogenesis
    Back
    Increased lipolysis, increased beta-oxidation, and increased acetyl-CoA
  36. Front
    Safety valve role of ketone bodies
    Back
    They provide energy when acetyl-CoA cannot enter the TCA cycle efficiently
  37. Front
    How ketone bodies help the brain
    Back
    They provide an alternative fuel and reduce dependence on glucose
  38. Front
    How ketone bodies affect protein breakdown
    Back
    They decrease the need for protein breakdown
  39. Front
    How ketone bodies protect muscle protein
    Back
    They reduce glucose demand and therefore reduce the need for gluconeogenesis from amino acids
  40. Front
    Main concept in extreme starvation
    Back
    Continued starvation eventually depletes energy stores and leads to failure
  41. Front
    Trigger for ketogenesis
    Back
    Low insulin and high glucagon
  42. Front
    Cause of ketogenesis
    Back
    Excess acetyl-CoA and low oxaloacetate
  43. Front
    How ketone bodies are transported
    Back
    They travel freely in blood because they are water-soluble
  44. Front
    Utilization of ketone bodies
    Back
    They are converted to acetyl-CoA and used to generate ATP
  45. Front
    Special rule for liver and ketone bodies
    Back
    The liver makes ketone bodies but cannot use them
  46. Front
    Special rule for red blood cells and ketone bodies
    Back
    Red blood cells cannot use ketone bodies
  47. Front
    Core rule of ketone metabolism
    Back
    Liver exports ketone bodies and other tissues use them
  48. Front
    Why acetyl-CoA accumulates during fasting
    Back
    Oxaloacetate is diverted to gluconeogenesis, limiting TCA cycle entry
  49. Front
    What are the three ketone bodies
    Back
    Acetoacetate, beta-hydroxybutyrate, and acetone
  50. Front
    Where are ketone bodies made
    Back
    In liver mitochondria
  51. Front
    Why can the liver not use ketone bodies
    Back
    It lacks SCOT
  52. Front
    Why ketone bodies are water-soluble but fatty acids are not
    Back
    Ketone bodies are smaller and more polar, allowing free transport in blood, whereas fatty acids are hydrophobic
  53. Front
    Effect of increased insulin on ketone production
    Back
    It decreases ketone production
  54. Front
    Cheat sheet trigger for ketogenesis
    Back
    Fasting causes low insulin and high glucagon
  55. Front
    Cheat sheet problem leading to ketogenesis
    Back
    Low oxaloacetate slows the TCA cycle while acetyl-CoA rises
  56. Front
    Cheat sheet solution to fasting acetyl-CoA excess
    Back
    Ketone body formation
  57. Front
    Cheat sheet ketone bodies
    Back
    Acetoacetate, beta-hydroxybutyrate, acetone
  58. Front
    Cheat sheet use of ketone bodies
    Back
    Converted to acetyl-CoA and then to ATP
  59. Front
    Cheat sheet special rules
    Back
    Liver cannot use ketone bodies and red blood cells cannot use ketone bodies

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