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Cholesterol and Its Derivatives

Tier 2 · #16 of 33 · high yield · topic 3.13 — every high-yield fact from the book chapter, exam-ready.

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  1. Front
    What is the rate-limiting (committed) enzyme of cholesterol synthesis?
    Back
    HMG-CoA reductase
  2. Front
    HMG-CoA reductase reduces HMG-CoA to which product?
    Back
    Mevalonate
  3. Front
    How many NADPH does HMG-CoA reductase consume per reaction ( HMG-CoA → mevalonate )?
    Back
    Two NADPH
  4. Front
    In which cellular compartment(s) does cholesterol synthesis occur?
    Back
    Cytosol and ER (entirely extramitochondrial )
  5. Front
    Cytosolic acetyl-CoA for cholesterol synthesis is exported from the mitochondria as which molecule?
    Back
    Citrate
  6. Front
    Which cytosolic enzyme cleaves citrate back into acetyl-CoA and oxaloacetate (consuming ATP)?
    Back
    ATP-citrate lyase (citrate lyase)
  7. Front
    Why must acetyl-CoA be ferried out as citrate for cholesterol synthesis?
    Back
    Acetyl-CoA cannot cross the inner mitochondrial membrane (it is impermeable to free CoA/acetyl-CoA)
  8. Front
    Statins lower plasma LDL by competitively inhibiting which enzyme?
    Back
    HMG-CoA reductase ( statins structurally mimic HMG-CoA )
  9. Front
    HMG-CoA reductase is active in which phosphorylation state?
    Back
    Dephosphorylated (active) ; phosphorylated = inactive
  10. Front
    Which kinase phosphorylates and INACTIVATES HMG-CoA reductase ?
    Back
    AMPK (AMP-activated protein kinase)
  11. Front
    AMPK is activated by what intracellular signal (energy state)?
    Back
    High AMP:ATP ratio (energy deficit)
  12. Front
    Which hormone promotes DEPHOSPHORYLATION (activation) of HMG-CoA reductase in the fed state?
    Back
    Insulin
  13. Front
    Which hormone promotes phosphorylation (inactivation) of HMG-CoA reductase in the fasting state?
    Back
    Glucagon
  14. Front
    Which transcription factor upregulates HMG-CoA reductase (and the LDL receptor) gene when intracellular cholesterol is LOW ?
    Back
    SREBP (Sterol Regulatory Element Binding Protein)
  15. Front
    When cholesterol is HIGH , where is the SREBP-SCAP complex retained, blocking gene transcription ?
    Back
    Retained in the ER membrane
  16. Front
    When cholesterol is low, the SREBP-SCAP complex travels to which organelle to be cleaved by S2P (site-2 protease) ?
    Back
    The Golgi
  17. Front
    Besides phosphorylation and transcription, what is the third regulatory mechanism controlling HMG-CoA reductase ?
    Back
    Accelerated proteasomal (ubiquitin-mediated) degradation of the enzyme, triggered by excess cholesterol and bile acids
  18. Front
    How many acetyl-CoA molecules are required to synthesize one cholesterol ?
    Back
    18 acetyl-CoA
  19. Front
    How many ATP and how many NADPH are required to synthesize one cholesterol ?
    Back
    36 ATP and 16 NADPH
  20. Front
    Cloze: Two acetyl-CoA condense to acetoacetyl-CoA via {{ thiolase }}, then a third acetyl-CoA joins to form {{ HMG-CoA }}.
    Back
    thiolase ; HMG-CoA
  21. Front
    In the MITOCHONDRIA , HMG-CoA is the substrate for which pathway (vs. cholesterol synthesis in the cytosol )?
    Back
    Ketogenesis (mitochondrial HMG-CoA → HMG-CoA lyase → ketone bodies)
  22. Front
    Stage 2 of cholesterol synthesis converts mevalonate into activated five-carbon units called what?
    Back
    Isoprene units ( isopentenyl pyrophosphate/IPP and dimethylallyl pyrophosphate/DMAPP )
  23. Front
    How many ATP are consumed per mevalonate to make the activated isoprene units ?
    Back
    Three ATP
  24. Front
    What is the name of the linear 30-carbon molecule formed by head-to-tail polymerization of six isoprene units ?
    Back
    Squalene
  25. Front
    Squalene is cyclized in the ER to form which first four-ring sterol intermediate?
    Back
    Lanosterol
  26. Front
    Classic trap: Once the four-ring sterol nucleus is built, can it be catabolized back to acetyl-CoA ?
    Back
    No — it cannot be broken down to acetyl-CoA/CO2 ; it must be excreted as bile acids
  27. Front
    What is the major route by which the liver eliminates cholesterol from the body?
    Back
    Conversion to bile acids
  28. Front
    What is the rate-limiting enzyme of bile acid synthesis?
    Back
    Cholesterol 7-alpha-hydroxylase ( CYP7A1 )
  29. Front
    Cholesterol 7-alpha-hydroxylase (CYP7A1) is feedback-inhibited by what?
    Back
    Bile acids returning via the enterohepatic circulation
  30. Front
    Primary bile acids are conjugated with which two molecules to keep them ionized across gut pH?
    Back
    Glycine or taurine
  31. Front
    Name the two PRIMARY bile acids made by the liver .
    Back
    Cholic acid and chenodeoxycholic acid
  32. Front
    Name the two SECONDARY bile acids produced by intestinal bacteria.
    Back
    Deoxycholic acid and lithocholic acid
  33. Front
    What percentage of bile acids is reabsorbed in the terminal ileum (enterohepatic circulation)?
    Back
    About 95%
  34. Front
    How do bile acid sequestrants (e.g., cholestyramine ) lower plasma cholesterol ?
    Back
    They trap bile acids in the gut , breaking enterohepatic recycling and forcing the liver to make fresh bile acids from cholesterol
  35. Front
    What is the rate-limiting step of ALL steroid hormone synthesis?
    Back
    Side-chain cleavage of cholesterol to pregnenolone by P450scc (CYP11A1)
  36. Front
    P450scc (CYP11A1) converts cholesterol to which 21-carbon intermediate?
    Back
    Pregnenolone
  37. Front
    On which membrane is P450scc (CYP11A1) located?
    Back
    The inner mitochondrial membrane
  38. Front
    Which common 21-carbon steroid (made from pregnenolone ) is the precursor for all subsequent steroid hormones ?
    Back
    Progesterone
  39. Front
    Which enzyme converts androgens to estrogens , and where?
    Back
    Aromatase ( CYP19A1 ), in the ovary and peripheral tissues
  40. Front
    Order by carbon count: cholesterol , glucocorticoids/mineralocorticoids , androgens , estrogens .
    Back
    Cholesterol 27C → glucocorticoids/mineralocorticoids 21C → androgens 19C → estrogens 18C
  41. Front
    Vitamin D synthesis begins in the skin from which cholesterol derivative?
    Back
    7-dehydrocholesterol
  42. Front
    What wavelength/type of radiation cleaves the B ring of 7-dehydrocholesterol in skin ?
    Back
    UVB radiation (295-300 nm)
  43. Front
    What is the active hormonal form of vitamin D ?
    Back
    1,25-dihydroxyvitamin D3 ( calcitriol )
  44. Front
    Which vitamin D form is the major CIRCULATING form, measured on a serum vitamin D test?
    Back
    25-hydroxyvitamin D3 (calcidiol / 25(OH)D)
  45. Front
    Which LIVER enzyme hydroxylates vitamin D3 at carbon 25?
    Back
    CYP2R1 (or CYP27A1 )
  46. Front
    Which KIDNEY enzyme adds the C-1 hydroxyl to ACTIVATE vitamin D (forming calcitriol )?
    Back
    1-alpha-hydroxylase ( CYP27B1 )
  47. Front
    Which KIDNEY enzyme hydroxylates at C-24 to INACTIVATE vitamin D ?
    Back
    24-hydroxylase ( CYP24A1 )
  48. Front
    Why does end-stage renal disease cause secondary hyperparathyroidism / renal osteodystrophy ( vitamin D mechanism)?
    Back
    Loss of renal 1-alpha-hydroxylase (CYP27B1) → 25(OH)D cannot become calcitriol → low intestinal Ca absorption → low serum Ca → high PTH
  49. Front
    What is the correct treatment for the vitamin D defect in end-stage renal disease ?
    Back
    Exogenous calcitriol (the active form), not vitamin D3
  50. Front
    Cytochrome P450 enzymes are what class of enzyme (oxygen handling)?
    Back
    Monooxygenases — incorporate one O atom into the substrate as -OH; the other O is reduced to H2O
  51. Front
    What is the electron donor for cytochrome P450 monooxygenase reactions?
    Back
    NADPH
  52. Front
    Which ER cytochrome P450 has broad substrate specificity, handling Phase I drug/xenobiotic detoxification and many drug-drug interactions?
    Back
    CYP3A4
  53. Front
    Which P450 enzyme is 7-alpha-hydroxylase , the rate-limiter of bile acid synthesis?
    Back
    CYP7A1
  54. Front
    Inside the mitochondria , which enzyme condenses acetyl-CoA with oxaloacetate to form citrate (the first step of the citrate shuttle)?
    Back
    Citrate synthase
  55. Front
    Vitamin D3 (cholecalciferol) is carried from the skin to the liver bound to which plasma transport protein?
    Back
    Vitamin D-binding protein (DBP)
  56. Front
    Cloze: In skin , UVB cleaves the B ring of 7-dehydrocholesterol to form {{ pre-vitamin D3 }}, which then heat-isomerizes to {{ vitamin D3 (cholecalciferol) }}.
    Back
    pre-vitamin D3 ; vitamin D3 (cholecalciferol)
  57. Front
    Is vitamin D3 (cholecalciferol) , the product made in the skin , biologically active or inactive?
    Back
    Inactive (it must be hydroxylated in liver then kidney to become active calcitriol )
  58. Front
    In MITOCHONDRIAL P450 reactions (e.g., P450scc ), which two iron-sulfur carriers shuttle electrons from NADPH to the P450 enzyme?
    Back
    Adrenodoxin reductase → adrenodoxin
  59. Front
    In the ENDOPLASMIC RETICULUM , electrons reach cytochrome P450 from NADPH via which carrier protein (vs. adrenodoxin in mitochondria)?
    Back
    NADPH-cytochrome P450 reductase
  60. Front
    What are the three direct downstream actions of calcitriol (active vitamin D ) as a nuclear-receptor ligand?
    Back
    Upregulates intestinal calcium AND phosphate absorption, and promotes bone mineralization
  61. Front
    By lowering intracellular cholesterol , statins release SREBP — what is the net effect on hepatic LDL receptors and plasma LDL?
    Back
    More LDL receptors on hepatocytes → increased clearance of LDL from blood → lower plasma LDL
  62. Front
    When cholesterol is abundant, sterols feed back to inactivate HMG-CoA reductase by promoting the phosphorylation of which kinase?
    Back
    AMPK
  63. Front
    Discrimination: are MITOCHONDRIAL biosynthetic P450 enzymes (e.g., CYP11A1 ) substrate-specific or broad-spectrum?
    Back
    Highly substrate-specific (one precise biosynthetic job), unlike broad-spectrum ER xenobiotic P450s such as CYP3A4
  64. Front
    Name two example statin drugs (competitive HMG-CoA reductase inhibitors).
    Back
    Lovastatin and atorvastatin
  65. Front
    The ~5% of bile acids that escape reabsorption and leave in the feces represents what for the body?
    Back
    The net cholesterol excretion route (the only way to eliminate the sterol nucleus)
  66. Front
    Two 15-carbon chains of which intermediate fuse tail-to-tail to form 30-carbon squalene ?
    Back
    Farnesyl pyrophosphate
  67. Front
    Which single endocrine organ makes glucocorticoids , mineralocorticoids , AND weak androgens (DHEA) ?
    Back
    The adrenal cortex
  68. Front
    Cloze: Vitamin D is activated by a three-organ relay: {{ skin }} (UVB) → {{ liver }} (C-25 hydroxyl) → {{ kidney }} (C-1 hydroxyl → calcitriol ).
    Back
    skin ; liver ; kidney
  69. Front
    What is the weak androgen produced by the adrenal cortex ?
    Back
    DHEA (dehydroepiandrosterone)
  70. Front
    In the SREBP-SCAP complex , what is the role of SCAP ?
    Back
    It is the escort/sensor protein that carries SREBP from the ER to the Golgi when cholesterol is low
  71. Front
    Why does conjugating bile acids with glycine or taurine (lowering their pKa) matter functionally?
    Back
    It keeps them ionized as bile salts across the full gut pH range, enabling fat emulsification
  72. Front
    Why does high carbohydrate intake (high insulin ) increase cholesterol synthesis?
    Back
    Insulin drives the fed state and glucose into cells, filling the cytosolic acetyl-CoA pool (via citrate export) that feeds cholesterol synthesis
  73. Front
    The fourth stage of cholesterol synthesis ( squalene → lanosterol cyclization in the ER ) requires which co-substrate?
    Back
    Molecular oxygen (O2) — it is an oxidative cyclization

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