Collagen & Glycoprotein

4 types of tissues in body:

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

Connective Tissue

• 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

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

• 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

• 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.

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

• 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

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

• 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

• 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

• 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

• 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