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BI6.1-3 | Extracellular Matrix — Gate Quiz
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Collagen is the most abundant protein in the human body. Which amino acid sequence is unique to collagen and essential for its triple helix formation?
Correct! Collagen has a unique Gly-X-Y repeating sequence where X is often proline and Y is often hydroxyproline. Glycine at every third position is essential because only Gly (smallest amino acid) fits in the tight interior of the triple helix.
Collagen triple helix: three polypeptide chains wound together. Glycine at every 3rd position is mandatory (fits in the narrow interior). Hydroxyproline stabilizes the helix via H-bonds. Hydroxylation of Pro and Lys requires vitamin C (ascorbate) as cofactor for prolyl and lysyl hydroxylases.
Incorrect. The Gly-X-Y repeating sequence (X = often Pro, Y = often Hyp) is unique to collagen.
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A sailor on a long voyage without fruits presents with perifollicular haemorrhages, bleeding gums, and poor wound healing. Deficiency of which vitamin impairs collagen synthesis?
Correct! Vitamin C (ascorbic acid) is required as a cofactor for prolyl hydroxylase and lysyl hydroxylase. Without hydroxylation of proline and lysine, collagen triple helix cannot form properly, leading to scurvy.
Scurvy (vitamin C deficiency): impaired collagen synthesis causes perifollicular haemorrhages, bleeding gums (scorbutic gums), corkscrew hair, poor wound healing, and bone pain in children. Vitamin C also maintains iron in Fe2+ form for absorption and is an antioxidant.
Incorrect. Vitamin C is the cofactor for proline and lysine hydroxylation in collagen synthesis.
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Which type of collagen is the most abundant, found in skin, bone, and tendons, and is deficient in osteogenesis imperfecta?
Correct! Type I collagen is the most abundant (90% of all collagen), found in skin, bone, tendons, ligaments, and cornea. Mutations in COL1A1/COL1A2 genes cause osteogenesis imperfecta (brittle bone disease).
Collagen types: Type I (skin, bone, tendons — most abundant), Type II (cartilage), Type III (blood vessels, foetal skin), Type IV (basement membrane, non-fibrillar). Ehlers-Danlos syndrome involves Type III or V defects. Alport syndrome involves Type IV (glomerular basement membrane).
Incorrect. Type I collagen is the most abundant and is deficient in osteogenesis imperfecta.
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Hyaluronic acid is a glycosaminoglycan (GAG) that is a major component of the extracellular matrix. Unlike other GAGs, hyaluronic acid is:
Correct! Hyaluronic acid is unique among GAGs: it is unsulfated, very large (up to millions of Da), and is NOT covalently linked to a core protein (unlike other proteoglycans). It provides turgor and lubrication.
GAGs include: hyaluronic acid (unsulfated, no protein link), chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin, keratan sulfate (all sulfated and proteoglycan-linked). GAGs are negatively charged due to sulfate and carboxylate groups, attracting cations and water (providing turgor). Important in joint fluid viscosity.
Incorrect. Hyaluronic acid is unsulfated and not covalently linked to a core protein.
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Fibronectin is an extracellular matrix glycoprotein that mediates cell adhesion. It binds cells via which integrin-recognition sequence?
Correct! Fibronectin contains the RGD (Arg-Gly-Asp) tripeptide sequence that is recognized by integrin receptors on cell surfaces, mediating cell-ECM adhesion.
Fibronectin functions: cell adhesion, migration, wound healing, and tissue organization. The RGD sequence is also found in vitronectin, osteopontin, and collagen. Fibronectin connects ECM components (collagen, heparan sulfate) to cell surface integrins, forming a scaffold for cell migration during development and wound healing.
Incorrect. The RGD (Arg-Gly-Asp) sequence in fibronectin is recognized by integrins.
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Elastin gives tissues like lung and blood vessel walls their elasticity. Which amino acids are unique crosslinks in elastin, not found in collagen?
Correct! Desmosine and isodesmosine are unique crosslinks formed from four lysine residues (three modified by lysyl oxidase) in elastin. These crosslinks give elastin its rubber-like elasticity.
Elastin synthesis: tropoelastin polypeptides with Gly, Pro, Val, Ala repeats; lysyl oxidase (copper-dependent) oxidizes lysine to allysine, then forms desmosine crosslinks. Marfan syndrome involves fibrillin-1 (scaffolding for elastin) mutations causing aortic aneurysm. Emphysema: elastin degraded by neutrophil elastase (alpha-1-antitrypsin protects).
Incorrect. Desmosine and isodesmosine are the unique crosslinks in elastin.
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In which cellular compartment does hydroxylation of proline residues in procollagen occur?
Correct! Proline hydroxylation by prolyl hydroxylase (requiring Vitamin C) occurs in the RER lumen as the procollagen chains are being synthesized and assembled.
Collagen synthesis steps: 1) Transcription/translation of alpha chains on RER ribosomes. 2) Hydroxylation of Pro and Lys in RER (Vitamin C cofactor). 3) Glycosylation in RER. 4) Triple helix formation (procollagen) in RER. 5) Transport to Golgi, packaging. 6) Secreted as procollagen. 7) Procollagen peptidase cleaves terminal propeptides extracellularly. 8) Fibril formation. 9) Lysyl oxidase crosslinking.
Incorrect. Hydroxylation of Pro and Lys in procollagen occurs in the RER.
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Hurler syndrome is caused by deficiency of alpha-L-iduronidase, leading to accumulation of heparan sulfate and dermatan sulfate. This is a type of:
Correct! Hurler syndrome (MPS Type I) is a mucopolysaccharidosis caused by alpha-L-iduronidase deficiency, leading to accumulation of glycosaminoglycans (heparan + dermatan sulfate) in lysosomes.
Mucopolysaccharidoses (MPS): all AR except Hunter (XLR). MPS I (Hurler): alpha-L-iduronidase, coarse facies, corneal clouding, intellectual disability. MPS II (Hunter): iduronate-2-sulfatase, XLR, no corneal clouding. MPS IV (Morquio): keratan sulfate accumulation, short stature, normal intelligence. Diagnosed by urine GAG excretion.
Incorrect. Hurler syndrome is a mucopolysaccharidosis (lysosomal storage of GAGs).
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Laminin is a major glycoprotein of the basement membrane. Together with Type IV collagen, it forms the scaffold of the basement membrane. Which disease involves autoantibodies against the glomerular basement membrane collagen (Type IV, alpha-3 chain)?
Correct! Goodpasture syndrome is caused by autoantibodies against the alpha-3 chain of Type IV collagen in the glomerular basement membrane and alveolar basement membrane, causing rapidly progressive glomerulonephritis and pulmonary haemorrhage.
Basement membrane components: Type IV collagen + laminin + nidogen + perlecan (heparan sulfate proteoglycan). Alport syndrome: GENETIC mutation in Type IV collagen genes (COL4A3/4/5). Goodpasture: AUTOIMMUNE anti-GBM antibodies. Both affect GBM but by different mechanisms.
Incorrect. Goodpasture syndrome involves anti-GBM autoantibodies against Type IV collagen alpha-3 chain.
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Osteogenesis imperfecta (brittle bone disease) is most commonly caused by mutations in genes encoding:
Correct! Osteogenesis imperfecta (OI) is most commonly caused by mutations in COL1A1 or COL1A2 genes encoding Type I collagen, which is the main collagen in bone.
Osteogenesis imperfecta: autosomal dominant (usually), blue sclerae (collagen in sclera), hearing loss (ossicular bone involvement), dental abnormalities (dentinogenesis imperfecta), easy fractures. Type I OI = quantitative defect (less collagen). Type II OI = qualitative defect (abnormal collagen), usually lethal. Treatment: bisphosphonates to increase bone density.
Incorrect. OI is caused by Type I collagen gene mutations (COL1A1/COL1A2).
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