Klappa

Public flashcard deck · 62 cards

Ketone Bodies

Tier 3 · #23 of 33 · moderate yield · topic 3.12 — every high-yield fact from the book chapter, exam-ready.

Study this deck free Add to my library

  1. Front
    What are the three ketone bodies?
    Back
    Acetoacetate , β-hydroxybutyrate , and acetone
  2. Front
    In which specific subcellular compartment and tissue does ketogenesis occur?
    Back
    The mitochondrial matrix of hepatocytes (liver)
  3. Front
    What metabolite is the direct substrate for ketone body synthesis?
    Back
    Acetyl-CoA (from β-oxidation of fatty acids )
  4. Front
    What is the single trigger condition that diverts acetyl-CoA into ketogenesis?
    Back
    Oxaloacetate depletion ( acetyl-CoA > oxaloacetate )
  5. Front
    Why is oxaloacetate depleted in the fasting/diabetic liver , linking gluconeogenesis to ketogenesis?
    Back
    Gluconeogenesis pulls oxaloacetate away from the TCA cycle to make phosphoenolpyruvate
  6. Front
    Cloze: Acetyl-CoA can only enter the TCA cycle by condensing with {{ oxaloacetate }} to form citrate .
    Back
    oxaloacetate
  7. Front
    Name the three physiological/clinical states that trigger ketogenesis.
    Back
    Fasting , starvation , and uncontrolled (type 1) diabetes
  8. Front
    Which enzyme catalyzes step 1 of ketogenesis (condensation of two acetyl-CoA )?
    Back
    Thiolase
  9. Front
    What product is formed when thiolase condenses two acetyl-CoA in step 1 of ketogenesis?
    Back
    Acetoacetyl-CoA
  10. Front
    Which enzyme catalyzes the committed, rate-limiting step of ketogenesis?
    Back
    HMG-CoA synthase (mitochondrial)
  11. Front
    What does mitochondrial HMG-CoA synthase produce by adding a third acetyl-CoA to acetoacetyl-CoA ?
    Back
    HMG-CoA (3-hydroxy-3-methylglutaryl-CoA)
  12. Front
    Ketogenic vs cholesterol-synthesis HMG-CoA synthase : how do they differ in location?
    Back
    Ketogenic HMG-CoA synthase is mitochondrial ; the cholesterol-synthesis one is cytosolic
  13. Front
    Which enzyme cleaves HMG-CoA into acetoacetate and acetyl-CoA ?
    Back
    HMG-CoA lyase
  14. Front
    Which ketone body is the primary one released into the blood directly from HMG-CoA cleavage?
    Back
    Acetoacetate
  15. Front
    Which enzyme reduces acetoacetate to β-hydroxybutyrate , and what is its electron donor?
    Back
    3-hydroxybutyrate dehydrogenase , using NADH
  16. Front
    Which ketone body is the most abundant in circulation (predominant form)?
    Back
    β-hydroxybutyrate (3-hydroxybutyrate)
  17. Front
    Why does β-hydroxybutyrate predominate in fasting and DKA ?
    Back
    Heavy fatty acid oxidation makes NADH very high , pushing the dehydrogenase toward the reduced form
  18. Front
    The β-hydroxybutyrate -to- acetoacetate ratio reflects what cellular parameter?
    Back
    The mitochondrial NAD+/NADH ratio
  19. Front
    Why is β-hydroxybutyrate not technically a ketone chemically, despite being a ketone body?
    Back
    It has a hydroxyl group, not a ketone group
  20. Front
    How is acetone formed from acetoacetate ?
    Back
    Spontaneous (non-enzymatic) decarboxylation
  21. Front
    Which ketone body is metabolically useless and simply exhaled?
    Back
    Acetone
  22. Front
    What clinical sign does exhaled acetone produce in uncontrolled diabetes ?
    Back
    Fruity (green-apple) smelling breath
  23. Front
    The single most-tested fact: can the liver oxidize the ketone bodies it makes?
    Back
    No — the liver produces but cannot oxidize ketone bodies
  24. Front
    Which enzyme does the liver lack, making it unable to use ketone bodies?
    Back
    SCOT (succinyl-CoA:acetoacetate CoA transferase / thiophorase)
  25. Front
    What reaction does SCOT (thiophorase) catalyze?
    Back
    Transfers a CoA group from succinyl-CoA to acetoacetate , forming acetoacetyl-CoA
  26. Front
    Besides the liver , which cell type cannot use ketone bodies, and why?
    Back
    Erythrocytes — they have no mitochondria
  27. Front
    In ketone utilization, which enzyme first oxidizes β-hydroxybutyrate back to acetoacetate ?
    Back
    3-hydroxybutyrate dehydrogenase (regenerating NADH )
  28. Front
    In ketone utilization, which enzyme cleaves acetoacetyl-CoA into two acetyl-CoA ?
    Back
    Thiolase
  29. Front
    What TCA cycle intermediate does SCOT consume as the CoA donor during ketone activation?
    Back
    Succinyl-CoA
  30. Front
    What is the activation 'cost' of ketone body utilization in energy terms?
    Back
    Diversion of one succinyl-CoA from the TCA cycle — equivalent to losing one GTP
  31. Front
    What is the net ATP yield per molecule of acetoacetate oxidized?
    Back
    19 ATP (20 from 2 acetyl-CoA minus 1 for activation)
  32. Front
    Name the tissues that oxidize ketone bodies for fuel.
    Back
    Muscle , heart , kidney , and (after days of starvation) the brain
  33. Front
    Under normal (fed) conditions, what is the brain 's near-exclusive fuel?
    Back
    Glucose
  34. Front
    At peak starvation, up to what fraction of the brain 's energy can ketone bodies supply?
    Back
    Up to two-thirds
  35. Front
    What is the survival benefit of the brain switching to ketone bodies in starvation?
    Back
    Less gluconeogenesis is needed, sparing muscle protein from catabolism
  36. Front
    Which hormones drive the fasted state that promotes ketogenesis?
    Back
    Glucagon and adrenaline (with low insulin )
  37. Front
    Which lipase do glucagon / adrenaline activate (via cAMP → PKA) to release fatty acids from adipose ?
    Back
    Hormone-sensitive lipase (HSL)
  38. Front
    What molecule is the master switch that inhibits CPT I and suppresses ketogenesis?
    Back
    Malonyl-CoA
  39. Front
    Which enzyme produces malonyl-CoA , and which hormone activates it?
    Back
    Acetyl-CoA carboxylase 1 (ACC1) , activated by insulin
  40. Front
    What does CPT I (carnitine palmitoyltransferase I) do?
    Back
    Transports long-chain acyl-CoA into the mitochondrial matrix
  41. Front
    In fasting, why is fatty acid import into mitochondria maximal?
    Back
    Low insulin → ACC1 inactive → malonyl-CoA low → CPT I uninhibited
  42. Front
    In the fed state, what happens to CPT I and ketogenesis?
    Back
    High insulin raises malonyl-CoA , blocks CPT I , and ketogenesis falls to ~zero
  43. Front
    What is the underlying cause of diabetic ketoacidosis (DKA) ?
    Back
    Zero insulin → unrestrained lipolysis and maximal ketogenesis
  44. Front
    Why do accumulating ketone bodies cause acidosis in DKA ?
    Back
    Acetoacetate and β-hydroxybutyrate are organic acids that dissociate and release protons, overwhelming bicarbonate
  45. Front
    What is the classic respiratory sign of DKA , and what is its purpose?
    Back
    Kussmaul breathing (deep, rapid) to blow off CO2 and compensate for the acidosis
  46. Front
    What lab findings characterize DKA ?
    Back
    High blood glucose , high anion gap , low bicarbonate , elevated serum ketones
  47. Front
    What is the definitive treatment for DKA ?
    Back
    Insulin (suppresses lipolysis, lowers glucagon , promotes glucose uptake)
  48. Front
    Why must potassium be monitored/replaced in DKA despite acidosis?
    Back
    Acidosis shifts K+ out of cells , masking total-body potassium depletion
  49. Front
    Conceptually, how does DKA differ from starvation ketosis?
    Back
    Same process, but DKA has zero insulin (no brake), so it runs unchecked; starvation retains some insulin
  50. Front
    What is the approximate pKa of acetoacetate ?
    Back
    ~3.6
  51. Front
    What is the approximate pKa of β-hydroxybutyrate ?
    Back
    ~4.7
  52. Front
    Why do acetoacetate and β-hydroxybutyrate dissociate fully and release protons at physiological pH?
    Back
    Their pKa values ( ~3.6 and ~4.7 ) are well below physiological pH , so they are essentially fully ionized organic acids
  53. Front
    Cloze: In DKA , accumulating ketone acids drive blood pH below {{7.35}}, sometimes to 7.0 or lower.
    Back
    7.35
  54. Front
    To what value can blood pH fall in severe DKA ?
    Back
    7.0 or lower
  55. Front
    Why can the brain NOT simply burn the fatty acids that flood the rest of the body during fasting?
    Back
    Long-chain fatty acids are too large and albumin-bound to efficiently cross the blood-brain barrier
  56. Front
    What physicochemical property lets ketone bodies cross the blood-brain barrier when fatty acids cannot?
    Back
    They are small and water-soluble (sufficiently polar)
  57. Front
    Why are ketone bodies an ideal exportable fuel from the liver ?
    Back
    They are water-soluble and freely cross cell membranes and the blood-brain barrier
  58. Front
    Ketone bodies vs free fatty acids : which property of ketone bodies makes them the fuel the brain can use in starvation?
    Back
    Ketone bodies are small and water-soluble (cross the BBB freely); free fatty acids are large and albumin-bound (excluded from the BBB)
  59. Front
    The thiolase that condenses two acetyl-CoA in ketogenesis is the same enzyme as which other pathway, running in which direction?
    Back
    The same thiolase from β-oxidation , run in the synthetic (reverse) direction under high acetyl-CoA conditions
  60. Front
    How many molecules of acetyl-CoA are consumed to build one HMG-CoA in ketogenesis?
    Back
    Three (2 condense via thiolase to acetoacetyl-CoA , then HMG-CoA synthase adds a third)
  61. Front
    Does the SCOT (thiophorase) activation of acetoacetate consume ATP directly?
    Back
    No — it transfers CoA from succinyl-CoA without spending ATP directly; the cost is the diverted succinyl-CoA (≈ one lost GTP)
  62. Front
    What does the brain upregulate during prolonged starvation to enable it to burn ketone bodies?
    Back
    SCOT (thiophorase) and the rest of the ketolytic machinery

Study these 62 cards with spaced repetition. Klappa is a free flashcard app: it schedules every card with FSRS-6, studies a deck as flashcards, multiple choice, typed answers or a graded test, and imports your Anki decks. How Klappa schedules reviews.

Sign in to study