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Calcium, Phosphorus & Biomineralization

New this year · #33 of 33 · on the outline, never on a past final · topic 4.10 — every high-yield fact from the book chapter, exam-ready.

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  1. Front
    Roughly what percentage of total body calcium resides in bone ?
    Back
    99%
  2. Front
    Which of the three blood calcium fractions is the ONLY biologically active form?
    Back
    Free ionized Ca²⁺ (~1.2 mmol/L)
  3. Front
    What total amount of calcium (in grams) does the adult body contain?
    Back
    ~1,000 g
  4. Front
    What percentage of total body phosphorus is skeletal ?
    Back
    85%
  5. Front
    In hypoalbuminemia , total calcium drops but ___ calcium remains normal.
    Back
    ionized (free)
  6. Front
    What is the normal serum phosphate range (mg/dL)?
    Back
    2.5–4.5 mg/dL
  7. Front
    Which inorganic phosphate species dominates in blood at physiological pH?
    Back
    HPO₄²⁻ (monohydrogen phosphate)
  8. Front
    Cytosolic Ca²⁺ (~0.1 µM) is roughly how many times lower than extracellular Ca²⁺?
    Back
    ~10,000× lower
  9. Front
    Which three pumps/exchangers keep cytosolic Ca²⁺ low?
    Back
    PMCA , NCX , and SERCA
  10. Front
    What is the archetypal EF-hand Ca²⁺ sensor that regulates over 100 targets?
    Back
    Calmodulin
  11. Front
    Which EF-hand protein triggers myocyte contraction when it binds calcium ?
    Back
    Troponin C
  12. Front
    Which two ER/SR luminal proteins bind calcium in bulk to serve as intracellular reservoirs?
    Back
    Calreticulin and calsequestrin
  13. Front
    Calbindin-D9k and calbindin-D28k are transcriptionally upregulated by which hormone?
    Back
    1,25(OH)₂D (calcitriol)
  14. Front
    Which bone Gla protein, a serum marker of osteoblast activity, contains vitamin K -dependent γ-carboxyglutamate residues?
    Back
    Osteocalcin
  15. Front
    Which secreted osteoblast glycoprotein physically bridges collagen to the growing mineral phase?
    Back
    Osteonectin
  16. Front
    What type of receptor is the calcium-sensing receptor (CaSR) ?
    Back
    A seven-transmembrane G-protein-coupled receptor
  17. Front
    When serum Ca²⁺ is HIGH, what happens to CaSR and PTH ?
    Back
    CaSR is activated (turned on) → PTH secretion is suppressed
  18. Front
    How many amino acids make up the mature PTH peptide?
    Back
    84 amino acids
  19. Front
    Which N-terminal portion of PTH is sufficient for full biological activity?
    Back
    The N-terminal 34 amino acids
  20. Front
    PTH binds its receptor (PTHR) on which bone cell — NOT directly on osteoclasts?
    Back
    Osteoblasts
  21. Front
    PTH drives osteoclast activation indirectly by increasing ___ and suppressing ___.
    Back
    RANKL↑ and OPG↓ (osteoprotegerin)
  22. Front
    What does OPG (osteoprotegerin) normally do?
    Back
    Acts as a decoy receptor that blocks RANKL
  23. Front
    Which cysteine protease, active at low pH, do osteoclasts secrete to digest the collagen matrix?
    Back
    Cathepsin K
  24. Front
    In the kidney , PTH stimulates reabsorption of ___ but inhibits reabsorption of ___.
    Back
    calcium (stimulated) ; phosphate (inhibited)
  25. Front
    PTH causes internalization of which two apical phosphate transporters in the proximal tubule ?
    Back
    NPT2a and NPT2c
  26. Front
    Which renal enzyme, stimulated by PTH , converts 25-hydroxyvitamin D to active calcitriol ?
    Back
    1α-hydroxylase (CYP27B1)
  27. Front
    Which two intestinal transcellular calcium -absorption components does calcitriol upregulate in enterocytes ?
    Back
    TRPV6 and calbindin-D9k
  28. Front
    Calcitriol completes negative feedback by acting through the VDR to do what to PTH ?
    Back
    Suppress PTH transcription
  29. Front
    Which cells secrete calcitonin ?
    Back
    Parafollicular C-cells of the thyroid
  30. Front
    What is calcitonin 's role in daily adult calcium homeostasis?
    Back
    A very limited (minor) role ; it inhibits osteoclasts and mainly limits maternal bone loss in pregnancy
  31. Front
    Which cells produce FGF23 in response to rising serum/dietary phosphate ?
    Back
    Osteocytes and osteoblasts
  32. Front
    FGF23 requires which transmembrane co-receptor to signal in the kidney ?
    Back
    Klotho
  33. Front
    What is FGF23 's net effect on renal phosphate handling?
    Back
    Phosphaturic — removes NPT2a/NPT2c , driving phosphate loss in the urine
  34. Front
    Besides causing phosphaturia, FGF23 inhibits which enzyme, lowering calcitriol ?
    Back
    Renal 1α-hydroxylase
  35. Front
    Which gene encodes the endopeptidase that cleaves and inactivates circulating FGF23 ?
    Back
    PHEX
  36. Front
    Loss-of-function PHEX mutations cause which inherited vitamin D -resistant rickets ?
    Back
    X-linked hypophosphatemia (XLH)
  37. Front
    Which intestinal transporter is the major route for dietary phosphate uptake?
    Back
    NPT2b
  38. Front
    Why does hypoparathyroidism RAISE serum phosphate ?
    Back
    Without PTH , urinary phosphate excretion drops, so phosphate is retained
  39. Front
    What is the most common cause of hyperphosphatemia ?
    Back
    Chronic kidney disease
  40. Front
    What is the chemical formula of hydroxyapatite ?
    Back
    Ca₁₀(PO₄)₆(OH)₂
  41. Front
    What is the primary mechanism of mineralization initiation in dentin, cementum, and cortical bone ?
    Back
    Matrix vesicle-mediated mineralization
  42. Front
    Which anionic membrane phospholipid in matrix vesicles electrostatically captures Ca²⁺ ?
    Back
    Phosphatidylserine
  43. Front
    Which annexin forms calcium channels in matrix vesicles and seeds nucleation?
    Back
    Annexin V
  44. Front
    Which enzyme hydrolyzes ATP to generate pyrophosphate (PPi) , the inhibitor of hydroxyapatite ?
    Back
    NPP1 (nucleotide pyrophosphatase/phosphodiesterase 1)
  45. Front
    What are the TWO simultaneous actions of TNAP on PPi/Pi in mineralization?
    Back
    Destroys the PPi inhibitor AND supplies Pi as a promoter
  46. Front
    Through which sodium/phosphate cotransporter is Pi imported into the matrix vesicle?
    Back
    PiT1
  47. Front
    What is the FIRST mineral phase to deposit (before crystalline hydroxyapatite )?
    Back
    Amorphous calcium phosphate (ACP)
  48. Front
    Why is a small permanent fraction of amorphous calcium salt beneficial?
    Back
    It dissolves rapidly to release calcium during acute hypocalcemia
  49. Front
    Approximately what percentage of dentin is mineral?
    Back
    ~70% mineral
  50. Front
    What is the dominant organic matrix protein of dentin ?
    Back
    Type I collagen (~90% of the organic matrix)
  51. Front
    Which collagen type is ABSENT from dentin because it would block mineralization?
    Back
    Type III collagen
  52. Front
    DPP and DSP are both cleavage products of which precursor protein?
    Back
    Dentin sialophosphoprotein (DSPP)
  53. Front
    Which two proteases cleave dentin phosphoproteins to convert them from inhibitors into inducers of mineralization?
    Back
    MMP-2 and MMP-20
  54. Front
    What is the approximate inorganic (mineral) content of enamel ?
    Back
    ~96% inorganic
  55. Front
    What is the key structural difference between enamel and dentin organic matrix?
    Back
    Enamel contains NO collagen (dentin is collagen-rich)
  56. Front
    What is the principal (hydrophobic) protein of the developing enamel scaffold?
    Back
    Amelogenin
  57. Front
    Which enzyme (enamelysin) cleaves amelogenin 's hydrophilic sections during enamel maturation?
    Back
    MMP-20
  58. Front
    In the FINAL enamel maturation stage, which protease digests the hydrophobic nanospheres for removal?
    Back
    KLK4 (kallikrein-4)
  59. Front
    What is TNAP 's membrane attachment mechanism?
    Back
    A GPI anchor (on the outer leaflet)
  60. Front
    What metal ions occupy TNAP 's active site?
    Back
    Two Zn²⁺ and one Mg²⁺ (it is a zinc metalloenzyme)
  61. Front
    TNAP deficiency causes which disease, via accumulation of PPi ?
    Back
    Hypophosphatasia
  62. Front
    Excess TNAP activity (e.g., in ACDC/CD73 deficiency) leads to what pathology?
    Back
    Pathological vascular calcification
  63. Front
    Which classic sign of hypocalcemia is carpopedal spasm called?
    Back
    Trousseau sign
  64. Front
    What is the most common cause of hypocalcemia ?
    Back
    Surgical damage or removal of the parathyroid glands
  65. Front
    Vitamin D -resistant rickets due to inability to make calcitriol is caused by deficiency of which enzyme?
    Back
    Renal 1α-hydroxylase
  66. Front
    In primary hyperparathyroidism , what are the levels of BOTH PTH and serum calcium ?
    Back
    Both are elevated
  67. Front
    An INACTIVATING CaSR mutation produces which condition (sensor never tells the gland to stop)?
    Back
    Familial hypocalciuric hypercalcemia
  68. Front
    Vitamin D toxicity causes hypercalcemia by which mechanism?
    Back
    Excess calcitriol drives intestinal absorption and bone resorption beyond excretory capacity
  69. Front
    Name one oral consequence of inadequate calcium intake during tooth development.
    Back
    Enamel hypoplasia (also: incomplete calcification, increased caries , alveolar bone resorption, delayed eruption)
  70. Front
    Which EF-hand protein acts as a slow-onset cytosolic Ca²⁺ buffer in fast-twitch muscle and distal convoluted tubule cells?
    Back
    Parvalbumin
  71. Front
    In distal convoluted tubule cells, parvalbumin shuttles Ca²⁺ toward which membrane for reabsorption?
    Back
    The basolateral membrane
  72. Front
    The chapter names three cytoplasmic sources of PPi . Which is the MAJOR source?
    Back
    Amino-acid activation for protein synthesis (aa + ATP → aa-AMP + PPi)
  73. Front
    Which PPi -generating reaction occurs in the nucleus during RNA synthesis?
    Back
    nNTP → nNMP + nPPi (nucleotide polymerization)
  74. Front
    Which PPi -generating reaction occurs in mitochondria during fatty-acid activation?
    Back
    R-COOH + ATP + HS-CoA → R-CO-SCoA + AMP + PPi
  75. Front
    Osteoclasts generate the H⁺ that dissolves bone mineral using carbonic anhydrase and which membrane pump?
    Back
    An H⁺-ATPase proton pump
  76. Front
    Write the carbonic anhydrase reaction osteoclasts use to acidify the resorption lacuna.
    Back
    CO₂ + H₂O → HCO₃⁻ + H⁺
  77. Front
    Which fast phase of PTH action pumps Ca²⁺ directly out of bone fluid WITHOUT destroying matrix?
    Back
    Osteocytic osteolysis (PTH stimulates the osteocytic membrane system)
  78. Front
    Besides PPi , name TWO physiological substrates of TNAP that accumulate in hypophosphatasia .
    Back
    Pyridoxal phosphate and phosphoethanolamine
  79. Front
    The chapter names TWO mechanisms of mineralization initiation. Besides matrix vesicle-mediated mineralization, what is the second?
    Back
    Heterogeneous nucleation on organized collagen matrices
  80. Front
    Of the protein-bound calcium fraction in blood, what is the albumin-to-globulin split?
    Back
    80% bound to albumin , 20% to globulins
  81. Front
    What fraction of blood phosphate is organically incorporated (and therefore NOT freely regulated/transportable)?
    Back
    70% (only the 30% inorganic Pi pool is regulated/transportable)
  82. Front
    What is the approximate HPO₄²⁻ : H₂PO₄⁻ ratio in blood at physiological pH?
    Back
    ~4:1
  83. Front
    A shift toward which phosphate species (favored by acidosis) is far more soluble?
    Back
    H₂PO₄⁻ (dihydrogen phosphate)
  84. Front
    When Ca²⁺ is high, CaSR signals through which G protein and effector to release ER Ca²⁺ and suppress PTH ?
    Back
    Gαq → phospholipase C → IP₃/DAG (IP₃ releases ER Ca²⁺)
  85. Front
    CaSR also couples to Gαi to suppress PTH gene expression — by lowering which second messenger?
    Back
    cAMP (Gαi → ↓ cAMP → ↓ PTH gene expression)
  86. Front
    PTH is synthesized as a preprohormone of how many amino acids before processing?
    Back
    110 amino acids (preprohormone → 90-aa prohormone → 84-aa mature)
  87. Front
    Why is much of PTH 's hormonal action fragment-mediated?
    Back
    The kidneys clear the intact molecule within minutes , but cleavage fragments circulate for hours
  88. Front
    During enamel maturation, amelogenin first self-assembles into structures of roughly what size?
    Back
    ~20 nm nanospheres
  89. Front
    What initially keeps nascent enamel hydroxyapatite crystals from fusing prematurely?
    Back
    Amelogenin nanospheres (hydrophilic tails outward) coating the crystal surfaces
  90. Front
    Besides amelogenin , name the three anionic minor proteins of the enamel scaffold.
    Back
    Ameloblastin , enamelin , and tuftelin
  91. Front
    Matrix vesicles are roughly what size, and bud from which three cell types?
    Back
    ~100 nm ; budding from osteoblasts, odontoblasts, and chondrocytes
  92. Front
    Inside the matrix vesicle, which orphan phosphatase releases Pi from phosphocholine?
    Back
    PHOSPH1
  93. Front
    What total amount of phosphorus (in grams) does the adult body contain?
    Back
    ~700 g
  94. Front
    Approximately how much calcium (mg) circulates in the blood (<0.1% of body total)?
    Back
    ~350 mg
  95. Front
    What structural motif defines the EF-hand calcium -binding proteins?
    Back
    A helix-loop-helix motif (cradles Ca²⁺ or Mg²⁺)
  96. Front
    Under what EC number is TNAP (tissue-nonspecific alkaline phosphatase) classified?
    Back
    EC 3.1.3.1 (orthophosphoric monoester phosphohydrolase, alkaline pH optimum)
  97. Front
    By what alternative name (its tissue origins) is TNAP also known?
    Back
    Liver-bone-kidney (LBK) alkaline phosphatase
  98. Front
    Besides phosphaturia and lowering calcitriol , what is FGF23 's third action — in the parathyroid gland ?
    Back
    It decreases PTH mRNA (lowers PTH; partly klotho-dependent, partly by raising VDR/CaSR expression)
  99. Front
    Which tissue is the hardest in the human body (and most heavily mineralized at ~96% inorganic)?
    Back
    Enamel
  100. Front
    An ACTIVATING (gain-of-function) CaSR mutation causes which calcium disturbance, and what happens to PTH ?
    Back
    Hypocalcemia — the sensor is permanently switched on, so PTH secretion is suppressed
  101. Front
    What is the most common cause of primary hyperparathyroidism (and thus hypercalcemia )?
    Back
    A single parathyroid adenoma
  102. Front
    Name two classic symptoms of hypercalcemia .
    Back
    Polyuria and polydipsia (also: constipation, nephrolithiasis , pancreatitis , altered mental status)

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