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Updated: 8/13/2021

Collagen

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  • Overview
  • Synthesis and Structure
    • Inside fibroblasts
      • pre-pro-collagen α chain formation
        • RER-bound ribosomes synthesize
        • contains hydrophobic translocation sequence
        • chain formed mainly of repeating tripeptide
          • Gly-X-Y
            • X and Y are proline, lysine
      • pro-collagen α chain formation
        • hydrophobic sequence cleaved
      • hydroxylated pro-collagen α chain formation
        • X and Y position prolines and lysines are hydroxylated to form hydroxylysine and hydroxyproline.
          • these amino acids are unique to collagen
          • hydroxylated as peptide chain passes into ER
          • performed by prolyl and lysyl hydroxylase
          • lack of lysyl hydroxylase function results in weak collagen chains
            • requires ascorbic acid (Vitamin C)
              • lack of vitamin C causes scurvy
                • presentation
                  • swollen gums, bruising, anemia, poor wound healing
            • can also be caused by defective lysyl hydroxylase gene
              • Ehlers-Danlos syndrome
                • nine different types
                • lysyl hydroxylase gene deficiency is one of many causes
                • presentation
                  • hyperextensible skin, hyperflexible joints, weak vessel walls (↑ risk for aneurysm)
      • glycosylated pro-collagen α chain formation
        • hydroxylysines are glycosylated
      • pro-collagen α chain trimer formation
        • three α chains associate
        • moved from RER to Golgi
        • secreted out of the fibroblast
    • Outside fibroblasts
      • collagen molecule (tropocollagen) formation
        • propeptides cleaved from ends and becomes insoluble
        • presence of propeptide does not allow assembly intracellularly
      • collagen fibril formation
        • catalyzed by lysyl oxidase
          • covalently links α chains by crosslinking hydroxylysines
          • copper required as cofactor
            • lack of copper results from Menkes disease
              • at low serum concentrations of copper this enzyme cannot function and weak collagen is formed
              • cause
                • X-linked gene mutation in ATP7A
                  • ATP-dependent copper efflux protein
                • aka Ehlers-Danlos syndrome type IX
                • inability of enterocytes to release absorbed copper
                • copper at toxic levels in small intestine and kidneys
                • copper in circulation and in brain at low levels
              • presentation
                • presents like a copper deficiency
                • seizures, failure to thrive, neurodegeneration
                • steel-colored and brittle hair
      • collagen fiber formation
        • fibrils aggregate to form final bundles of triple helix quaternary protein structure
  • Collagen Types
    • Type I
      • thick, rope-like bundles of collagen
        • strongest tensile form of collagen
      • majority of collagen in the body (approx. 90%)
      • found in locations where high tensile strength is needed
        • bone, fascia, tendons, teeth (dentin), cornea, skin
        • type III of early wound repair converted to type I in late wound repair
      • defective in osteogenesis imperfecta (OI) type I
        • aka brittle bone disease
        • AD, in most cases
        • presentation
          • multiple fractures with minimal force
            • first fractures may occur during delivery in severe form caused by collagen mutation
            • fractures will be milder and occur later in childhood with collagen deletion
          • blue sclerae
            • due to the translucency of the connective tissue over the choroid due to lack of collagen
          • deafness (50%)
            • abnormal middle ear bones
          • dental abnormalities
        • may be confused with child abuse
      • defective in various forms of Ehlers-Danlos syndrome
        • faulty collagen synthesis
        • see above
    • Type II
      • spongy collagen to absorb shock
      • found in tissues where there are compression forces
        • cartilage (including hyaline), vitreous body of the eye, nucleus pulposus of vertebral disc
    • Type III
      • web-like fibers where forces pull from many directions
        • aka reticulin
      • found in tissues where strength is needed (but not compression or tensile)
        • skin, blood vessels, uterus, fetal tissue
        • granulation tissue
          • type III of early wound repair converted to type I in late wound repair
      • defective in Ehlers-Danlos type IV
        • faulty collagen synthesis
        • associated with
          • joint dislocation
          • berry aneurysms
          • organ rupture
        • see above
    • Type IV
      • basement membrane
        • especially kidney, ears, eyes, skin
      • organizes/solidifies cellular structure
      • defective in Alport's syndrome
        • effects the tissues where type IV is most prominent
          • kidney → progressive hereditary nephritis
          • ears → deafness
          • eyes → ocular disturbances
        • majority of cases are X-linked dominant
      • one of the causes of epidermolysis bullosa
        • weak union of dermis and epidermis of the skin
        • easily formed blisters
      • Goodpasture's syndrome involves an auto-antibody against collagen type IV in pulmonary and glomerular capillaries
        • presents with hemoptysis and glomerular disease

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(M1.BC.15.74) A 29-year-old female presents to her psychiatrist with concerns that she may be "OCD." She explains that she has become extremely obsessed with making sure that her fruits and vegetables are completely sanitized by first rinsing with water for exactly 60 seconds and then boiling for exactly 60 minutes. She refuses to eat any fruits or vegetables that did not undergo this process, which she began doing about 3 months ago. Which of the following vitamin deficiencies is she most likely to develop?

QID: 106633

Vitamin A

5%

(19/360)

Vitamin K

6%

(23/360)

Vitamin C

81%

(293/360)

Vitamin D

1%

(5/360)

Vitamin E

4%

(16/360)

M 2 D

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(M1.BC.15.74) Collagen is a very critical structural protein in many of our connective tissues. Defects in collagen produce diseases such as Ehlers-Danlos syndrome, where there is a defective lysyl hydroxylase gene, or osteogenesis imperfecta, where there is a defect in the production of type I collagen. Which of the following represents the basic repeating tripeptide of collagen?

QID: 106618

Ser-X-Y

2%

(4/241)

Met-X-Y

1%

(3/241)

Gly-X-Y

88%

(213/241)

Glu-X-Y

5%

(11/241)

Asp-X-Y

2%

(4/241)

M 1 E

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(M1.BC.14.70) A first-year medical student undergoes a surgical procedure involving a midline laporotomy incision. The patient presents back to the surgeon approximately 3 months later and asks the surgeon: "What type of tissue is causing the scar to form on my abdomen?" The physician promptly answers:

QID: 106488

Keratin

4%

(11/252)

Type 1 collagen

63%

(160/252)

Type 2 collagen

8%

(19/252)

Type 3 collagen

19%

(47/252)

Type 4 collagen

4%

(10/252)

M 1 E

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