4 types of tissues in body:

  • Epithelial tissue
  • Muscular tissue
  • Nervous tissue
  • Connective tissue

Connective Tissue

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  • Specialized connective tissue
    • blood
    • bone
    • cartilage
      • existing within many joints
      • composed of specialized cells
        • chondrocytes
        • produced large amount of extracellular matrix
          • collagen fibres
          • ground substance (rich in proteoglycans)
          • elastin fibres
      • 3 types of cartilage
        • Elastic cartilage
        • Hyaline cartilage (articular cartilage)
          • type 2 collagen
            • rich in collagen & proteoglycan
          • hard, translucent
          • covers end of bones
          • age related changes (degeneration, eg. osteoarthritis)
            • fibrillation of the articular surface
            • decrease in the size and aggregation of proteoglycans
            • increased collagen crosslinking
            • loss of tensile strength
            • stiffness
        • Fibrocartilage
  • Component of CT consists of
    • cells
    • matrix (see below)
      • composition & ratio determines the type of CT

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2 classes of macromolecules that make up the extracellular matrix of CT

  • Glycoaminoglycans (GAGs)
    • unbranched polysaccharide chains composed of 2 repeating dissacharide unit
      • sugars
        • N-acetylgalactosamine
        • N-acetylglucosamine
        • Uronic acid
    • occupy large amount of space in extracellular matrix
    • it forms hydrated gels, thus enables them to withstand
      compressive forces
      • hydrophilic & –vely charged
    • 4 types of GAGs
      • Hyaluronic acid
      • Chondroitin sulphate
      • Heparan sulphate
      • Keratan sulphate
    • *see proteoglycan below
  • Fibrous proteins
    • structural
      • collagen
      • elastin
    • adhesive
      • fibronectin

Proteoglycans

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  • Proteoglycan are GAGs
    • except hyaluronic acid attached to the protein
  • Function
    • Regulate activities of signalling molecules
      • GAG portion acts as sieve
        • select molecules according to size and charge
    • Acts as cell surface receptors
    • Form huge polymeric molecules in cartilage or basal lamina

Collagen

  • most abundant protein
  • main protein in CT
  • organised into insoluble fibres of great tensile strength
    • suits its function as
      • component of CT (eg bone, tendon etc)
      • While in some tissues, like extracellular matrix, its dispersed as a gel

Structure

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  • long, rigid structure
    • composed of 3 interwoven α-polypeptide chains
      • tripeptide
      • -Gly-X-Y- [ (-Gly-Pro-Hyp-)333 ]
        • X: Proline
        • Y: Hydroxyproline/Hydroxylysine
    • held together by hydrogen bonds

Types

Different combinations of α-polypeptide chains form different types of collagen.

image

Type 1: (α1)2α2   ,    Type 2: (α1)3

Types:

  • Fibril-forming collagen
    • typical rope like structure
  • Network-forming collagen
    • forms a 3D mesh
  • Fibril-associated collagen
    • Binds to collagen fibrils and extracellular matrix

Synthesis

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  • Hydroxylation of proline and lysine
    • important in stabilizing the structure of collagen
    • hydroxylated residues appear only after collagen polypeptides are synthesise
    • enzyme that converts Pro to Hyp is prolyl hydroxylase
      • requires ascorbic acid (Vit C) to maintain its enzymatic activity
      • Hyp confers stability upon collagen
  • Glycosylation
    • glucose or galactose are sometimes attached to the hydroxylysine residues

Degradation

  • Collagen are dynamic and constantly undergo remodelling
    • in response to growth/injury
  • Accomplished by a family of collagenases
    • cleave intact collagen fibres into smaller fragments
    • these fragments can be phagocytosed and degraded by lysozyme to their constituent amino acid

Diseases

  • Rare heritable disorders of collagen
    • amino acid substitution/deletion in collagen polypeptide
    • deficiency in particular type of collagen
    • abnormal activity of collagen processing enzyme

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  • Scurvy
    • deficiency of ascorbic acid
      • required by prolyl hydroxylase
    • skin lesion
    • blood vessels fragility

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  • Ehler’s Danlos syndrome
    • heterogeneous group of connective tissue disorders
      • inheritable defects in the metabolism of collagen molecule
    • Disorders:
      • Deficiency of enzymes like lysyl hydroxylase
      • Mutations in amino acid sequence
        • most commonly type III collagen
    • Characterised by:
        • stretchy skin
        • loose joints

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  • Osteogenic Imperfecta
    • also known as ‘Brittle Bone syndrome’
      • easily bend & fracture
      • retarded wound healing
    • mutation in either gene
      • alpha 1
      • alpha 2
    • mutation results in abnormal triple-helical conformation

Collagen & Aging

Collagen Theory of Aging

  • with age, collagen gets older
  • old collagen gets stiff and not as flexible
  • causing problems such as
    • hypertension (vessels cant expand enough)
    • organs malfunction (stiffness)
    • hinders metabolic reaction

Wrinkles

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  • Due to changes in
    • reduced collagen
      • decreased protein synthesis
      • affect collagen type 1 & 3 in dermis
    • reduced elastin
    • general atrophy in extracellular matrix
      • due to reduced fibroblasts

Elastin

image

  • CT with rubber-like properties
  • Found in
    • lungs
    • blood vessel walls
    • elastic ligaments
  • Structure:
    • small non polar aa composition
      • valine
      • glycine
      • alanine
      • lysine & proline (but little hydroxylation)
  • Elastase enzyme (arise from neutrophil)
    • breakdown elastin
    • α1- anti-trypsin prevents elastase action
      • deficiency will lead to emphysema
      • degradation of alveolar walls in lungs
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Terri is obsessed with making medical school as painless as possible. She studies and compiles medical school notes in a concise, easy-to-understand format. She also enjoys reading contributions by others. She is an investor in sustainability projects. Her ideal weekend is wine tasting and experimenting on bread-making. She has yet to master the art of Sourdough baking.

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