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Extracellular Matrix and Oral Biochemistry

Tier 4 · #30 of 33 · lower yield · topic 1.6 — every high-yield fact from the book chapter, exam-ready.

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  1. Front
    What are the three functional categories of ECM components ?
    Back
    Structural fibrillar proteins ( collagen , elastin ); adhesive glycoproteins ( fibronectin , laminin ); GAGs and proteoglycans .
  2. Front
    Which cells produce the ECM of ordinary connective tissue?
    Back
    Fibroblasts and fibrocytes .
  3. Front
    Which cells produce dentin ECM?
    Back
    Odontoblasts .
  4. Front
    Approximately what fraction of total body protein is collagen ?
    Back
    About 30% .
  5. Front
    What is the repeating tripeptide motif of every collagen ?
    Back
    Gly–X–Y (X often proline , Y often hydroxyproline ).
  6. Front
    Why must glycine occupy every third residue in collagen ?
    Back
    It is the only amino acid small enough to fit into the core of the triple helix .
  7. Front
    What is the chain composition of type I collagen ?
    Back
    Heterotrimer : two α1 chains + one α2 chain (α1²α2).
  8. Front
    Type II collagen is the homotrimer (α1³) characteristic of which tissue?
    Back
    Cartilage .
  9. Front
    Which disease results from replacing glycine with a bulkier residue in collagen (dominant mutation)?
    Back
    Osteogenesis imperfecta ( brittle bones ).
  10. Front
    Collagen prolyl and lysyl hydroxylation requires which three factors?
    Back
    Molecular O₂ , Fe²⁺ , and vitamin C (ascorbic acid) .
  11. Front
    Which two enzymes hydroxylate collagen's proline and lysine residues?
    Back
    Prolyl hydroxylase and lysyl hydroxylase .
  12. Front
    What deficiency blocks collagen prolyl/lysyl hydroxylation , preventing stable triple-helix formation?
    Back
    Vitamin C deficiency ( scurvy ).
  13. Front
    Name three clinical features of scurvy .
    Back
    Reduced connective tissue strength , impaired wound healing , and tooth loss .
  14. Front
    Procollagen is converted to ______ by proteolytic removal of its non-helical propeptide extensions.
    Back
    Tropocollagen .
  15. Front
    What characteristic banding pattern do assembled collagen fibrils show?
    Back
    64 nm banding pattern .
  16. Front
    Which enzyme cross-links mature collagen by oxidizing lysine to allysine ?
    Back
    Lysyl oxidase (LOX) .
  17. Front
    Lysyl oxidase (LOX) requires which metal cofactor?
    Back
    Copper (Cu²⁺) .
  18. Front
    What is the consequence of LOX inhibition or copper deficiency for collagen?
    Back
    Collagen fibers remain weak and prone to failure ( defective cross-linking ).
  19. Front
    What does elastin do that collagen does not?
    Back
    Allows tissue to stretch and spring back to its original shape ( elastic recoil ).
  20. Front
    Which residues populate elastin 's hydrophobic (elastic recoil) domains?
    Back
    Val, Pro, and Gly .
  21. Front
    What is the soluble monomeric precursor of elastin called?
    Back
    Tropoelastin (TE) .
  22. Front
    Name the three structural features elastin LACKS compared to collagen .
    Back
    Lacks the Gly–X–Y repeat , lacks hydroxylysine , and has very few hydroxylated prolines .
  23. Front
    Which microfibrils form the scaffold onto which tropoelastin is deposited?
    Back
    Fibrillin microfibrils (fibrillin-1 and fibrillin-2).
  24. Front
    What unique cross-link links elastin chains (1 lysine + 3 allysines)?
    Back
    Desmosine or isodesmosine .
  25. Front
    What is the approximate half-life of elastin ?
    Back
    About 70 years (synthesized mainly in fetal/childhood life, essentially irreplaceable in adults ).
  26. Front
    Which conserved tripeptide motif in fibronectin binds cell-surface integrins ?
    Back
    RGD (Arg-Gly-Asp) .
  27. Front
    Besides fibronectin , which two other ECM molecules contain the RGD motif?
    Back
    Laminin and type IV collagen .
  28. Front
    What is the main non-collagen protein of dental pulp , mostly associated with type III collagen ?
    Back
    Fibronectin .
  29. Front
    Fibronectin binds simultaneously to which four partners?
    Back
    Collagen , proteoglycans , integrins , and fibrin .
  30. Front
    After type IV collagen , what is the most abundant protein of the basement membrane ?
    Back
    Laminin .
  31. Front
    What is laminin 's key functional effect on cells (contrast with fibronectin )?
    Back
    It inhibits cell movement ( maintains tissue phenotype/differentiation ).
  32. Front
    Defects in laminin-5 or laminin-6 cause which blistering disorder?
    Back
    Epidermolysis bullosa .
  33. Front
    Which acidic phosphorylated enamel glycoprotein binds hydroxyapatite and inhibits crystal growth ?
    Back
    Enamelin .
  34. Front
    A mutation in the ENAM gene causes which developmental enamel disorder?
    Back
    Amelogenesis imperfecta .
  35. Front
    DSPP (dentin sialophosphoprotein) is cleaved into which two proteins?
    Back
    Dentin phosphoprotein (DPP) and dentin sialoprotein (DSP) .
  36. Front
    Which mineralizing-tissue protein has binding sites for BOTH collagen and hydroxyapatite , physically linking them?
    Back
    Osteonectin .
  37. Front
    Elevated levels of which phosphorylated calcium-binding glycoprotein mark inflammation and epithelial cell transformation ?
    Back
    Osteopontin .
  38. Front
    A GAG disaccharide unit pairs an amino sugar with which two possible uronic acids?
    Back
    Glucuronic acid or iduronic acid (paired with N-acetylglucosamine or N-acetylgalactosamine ).
  39. Front
    What gives sulfated GAGs their defining intense negative charge?
    Back
    The addition of sulfate groups .
  40. Front
    Proteoglycans are up to 95% carbohydrate; glycoproteins are only ____ carbohydrate.
    Back
    1–60% (and branched rather than straight chains).
  41. Front
    Which GAG lacks sulfate residues AND does not covalently attach to a protein core?
    Back
    Hyaluronic acid (hyaluronan) .
  42. Front
    Hyaluronic acid is made of which two sugars?
    Back
    D-glucuronic acid and N-acetylglucosamine .
  43. Front
    How do high- vs low-molecular-weight hyaluronic acid fragments differ in effect?
    Back
    High MW HA is anti-inflammatory/anti-angiogenic ; small HA fragments are pro-inflammatory distress signals .
  44. Front
    Sulfated GAG gels resist compression; what counterbalances their osmotic swelling pressure?
    Back
    Tension in the collagen fiber network .
  45. Front
    Which activated sugar donors are used in proteoglycan/GAG synthesis?
    Back
    UDP-sugars .
  46. Front
    Which donor provides sulfate groups during GAG sulfation?
    Back
    PAPS (3'-phosphoadenosine-5'-phosphosulfate).
  47. Front
    Which enzyme converts glucuronic acid to iduronic acid in GAG chains?
    Back
    An epimerase .
  48. Front
    What is the major proteoglycan of cartilage ?
    Back
    Aggrecan .
  49. Front
    Which named proteoglycan is the smallest, carrying only 1 GAG chain (~40 kDa core)?
    Back
    Decorin .
  50. Front
    What percentage of enamel is inorganic, and how much collagen does it contain?
    Back
    ~96% inorganic ; NO collagen (the only tooth structure without it).
  51. Front
    Which collagen type is specifically ABSENT from dentin , and why?
    Back
    Type III collagen — because it can block mineralization .
  52. Front
    What is the dominant organic component (~90% of organic solids) of dentin ?
    Back
    Type I collagen (with small amounts of type V ).
  53. Front
    How does cementum 's collagen profile differ from dentin 's?
    Back
    Cementum contains type I (90%) AND type III (5%); dentin has type I but NO type III .
  54. Front
    What is the collagen profile of dental pulp ?
    Back
    Type I (56%) , type III (41%) , type V (2%) — high type III gives soft-tissue elasticity.
  55. Front
    Which ion does pulp chondroitin sulfate bind, and why does it matter?
    Back
    Ca²⁺ — maintaining the high pulp calcium concentration needed to mineralize dentin .
  56. Front
    What defines matrix metalloproteinases (MMPs) catalytically?
    Back
    Dependence on metal ions — most commonly zinc ( Ca²⁺ also involved) — for activity.
  57. Front
    Which MMP subclass (MMP-2, -9) degrades type IV collagen of the basement membrane?
    Back
    Gelatinases .
  58. Front
    What is the conserved zinc-binding motif of the MMP catalytic domain?
    Back
    HEXXGHXXGXXH (three histidines coordinate the zinc ).
  59. Front
    At what pH are MMPs catalytically active?
    Back
    Neutral pH .
  60. Front
    MMPs are synthesized and secreted in what form?
    Back
    Inactive preproenzymes ; secreted as proenzymes (require prodomain removal to activate).
  61. Front
    Which cytokines induce MMP gene transcription?
    Back
    IL-1 , TNF-α , EGF , and VEGF .
  62. Front
    Which factors INHIBIT MMP secretion at the transcriptional level?
    Back
    TGF-β and steroid hormones .
  63. Front
    Which specific inhibitors block MMP activity, and which three inhibit ALL MMPs?
    Back
    TIMPs (1–4) ; TIMP-1, TIMP-2, and TIMP-4 inhibit all MMPs.
  64. Front
    Which two non-specific plasma proteins also inhibit MMPs ?
    Back
    Alpha-2-macroglobulin and alpha-1-antiproteinase .
  65. Front
    Which MMP is the key mediator of periodontal collagen destruction ?
    Back
    MMP-8 (collagenase-2) , released by neutrophils .
  66. Front
    In a healthy periodontium, in what form does MMP-9 exist?
    Back
    Only the inactive/latent form — active MMP-9 signals pathology .
  67. Front
    Describe the caries mechanism by which MMPs degrade dentin collagen.
    Back
    Bacterial acids lower pH and demineralize dentin , exposing/activating MMPs; after salivary buffering restores pH, activated MMPs degrade the exposed collagen .
  68. Front
    In cancer, elevated expression of which MMP correlates with stage, metastasis, and survival in oropharyngeal cancer ?
    Back
    MMP-2 (a potential prognostic marker; MMP-9 shows no such correlation ).
  69. Front
    How many collagen types exist, and how many genes encode them?
    Back
    28 types encoded by 45 genes .
  70. Front
    In which tissues is type I collagen the dominant structural collagen?
    Back
    Bone, dentin, cementum, tendon, and skin .
  71. Front
    On which organelle does collagen synthesis begin, and what targets the pro-α chain there?
    Back
    The rough endoplasmic reticulum (RER) ; an N-terminal signal peptide targets the chain to the ER lumen .
  72. Front
    In collagen synthesis, which two sugars are added to hydroxylysine residues during glycosylation ?
    Back
    Glucose and galactose .
  73. Front
    In which region of the pro-α chain do disulfide bridges form before triple-helix assembly?
    Back
    The non-helical propeptide regions .
  74. Front
    Place the four collagen post-translational steps in order after the signal peptide is cleaved.
    Back
    (1) Hydroxylation of Pro/Lys , (2) glycosylation of hydroxylysine with glucose+galactose, (3) disulfide-bridge formation in the propeptides, (4) triple-helix assembly into procollagen .
  75. Front
    What is the function of the 'gaps' within assembled collagen fibrils in bone and teeth?
    Back
    They serve as nucleation sites for biomineralization (and scaffolds for non-collagen ECM proteins).
  76. Front
    Which residues populate elastin 's hydrophilic domains, and what is their function?
    Back
    Lys and Ala ; they are the cross-linking sites .
  77. Front
    After secretion, what escorts tropoelastin to the extracellular space?
    Back
    An elastin-binding protein chaperone .
  78. Front
    Which protein directs premature elastin clusters onto fibrillin microfibrils ?
    Back
    Fibulin-5 .
  79. Front
    Besides pulp, in which three tissue sites is elastin abundant?
    Back
    Lungs , large arteries , and elastic ligaments .
  80. Front
    Elastin is encoded by ___ gene(s), with diversity generated by ___.
    Back
    One gene ; alternative splicing .
  81. Front
    Which γ-carboxyglutamic-acid-containing non-collagen protein is found in dentin and cementum ?
    Back
    Osteocalcin .
  82. Front
    What is the function of ameloblastin in enamel?
    Back
    It regulates the process of amelogenesis .
  83. Front
    What is the function of tuftelin in enamel?
    Back
    It is phosphorylated and involved in early enamel mineralization .
  84. Front
    In which tissue is hyaluronic acid the most abundant GAG, and what fraction of total body HA is there?
    Back
    Skin — about 50% of total body HA.
  85. Front
    Name three sites besides skin where hyaluronic acid is found.
    Back
    Vitreous body of the eye , umbilical cord , and synovial fluid .
  86. Front
    How does tissue hyaluronic acid change with wound healing versus with aging?
    Back
    It increases during wound healing (post-injury) and decreases with age (contributing to skin aging).
  87. Front
    What molecules pass freely through the GAG gel's size-selective filter, and which are slowed?
    Back
    Ions (e.g., Ca²⁺ ) and small molecules pass freely; proteins and migrating cells are slowed .
  88. Front
    Why is the GAG filter function critical in the tooth specifically?
    Back
    It controls dentin mineralization and regulates nutrient diffusion in the pulp .
  89. Front
    Match each MMP substrate class to its members: collagenases, stromelysins, matrilysins, membrane-type.
    Back
    Collagenases = MMP-1, -8, -13, -18 ; stromelysins = MMP-3, -10, -11; matrilysins = MMP-7, -26; membrane-type = MMP-14, -15, -16, -17, -24, -25.
  90. Front
    In the MMP prodomain, what keeps the enzyme latent, and how?
    Back
    A cysteine motif (cysteine switch) that blocks the active site .
  91. Front
    Which MMP domain handles substrate recognition, ECM binding, and inhibitor interaction?
    Back
    The hemopexin (Hpx) domain .
  92. Front
    What unique catalytic-domain feature lets gelatinases (MMP-2/-9) bind collagen and gelatin ?
    Back
    A fibronectin type II-like insert .
  93. Front
    List the non-proteolytic activators that can remove the MMP prodomain.
    Back
    Reactive oxygen species (ROS) , lowered pH , oxidized glutathione (GSSG) , and elevated temperature.
  94. Front
    Besides cytokines, which hormone and which bacterial product upregulate MMP transcription?
    Back
    Parathyroid hormone (PTH) and bacterial LPS .
  95. Front
    What is the periodontal function of MMP-1 , and which cells make it?
    Back
    It regulates connective tissue composition ; synthesized by fibroblasts and keratinocytes .
  96. Front
    MMP-13 is produced by which cells, and what role does it play in periodontal inflammation?
    Back
    Osteoblasts ; it activates MMP-9 and the cascade can overcome TIMP inhibition .
  97. Front
    How do MMPs undermine dental fillings over time?
    Back
    They degrade the incompletely resin-infiltrated collagen of the hybrid (resin-dentin bonding) layer , weakening the adhesive bond.
  98. Front
    Which cells produce cartilage ECM, and which produce bone ECM?
    Back
    Chondroblasts/chondrocytes make cartilage ECM; osteoblasts/osteocytes make bone ECM.
  99. Front
    Besides lysyl oxidase , which enzyme also participates in collagen cross-linking?
    Back
    Transglutaminase .
  100. Front
    What is the structure of fibronectin ?
    Back
    A fucosylated glycoprotein dimer linked by disulfide bridges; each subunit is ~220 kDa.
  101. Front
    How does fibronectin expression change during dentin repair?
    Back
    It increases (reflecting its role in wound-healing/cell-migration responses).
  102. Front
    Laminin binds which three partners?
    Back
    Type IV collagen , heparan sulfate (a GAG), and cell-surface integrins .
  103. Front
    Which glycoprotein is the dominant one during enamel development (but is largely lost in mature enamel)?
    Back
    Amelogenin .
  104. Front
    What is the proteoglycan/GAG profile of dental pulp ?
    Back
    Chondroitin-4- and -6-sulfate (~60%) , dermatan sulfate (~34%) , keratan sulfate (~2%).
  105. Front
    By what mechanism do sulfated GAGs draw water into the ECM gel?
    Back
    Their high negative charge attracts Na⁺ ions osmotically, which pulls in large volumes of water (creating high osmotic/swelling pressure).
  106. Front
    In chronic periodontitis , where is the gelatinase MMP-2 detected?
    Back
    In the gingival pocket epithelium .
  107. Front
    Which cells synthesize tropoelastin ?
    Back
    Fibroblasts , smooth muscle cells , chondrocytes , and epithelial cells .
  108. Front
    What is the subunit structure of laminin (contrast with the fibronectin dimer)?
    Back
    A heterotrimeric glycoprotein built from α, β, and γ subunits .
  109. Front
    Where in the cell/matrix does lysyl oxidase (LOX) act on collagen and elastin?
    Back
    Extracellularly (it is a secreted/extracellular enzyme; in contrast, hydroxylation and glycosylation occur intracellularly in the ER ).

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