Collagen

COLLAGEN
  • Collagen is the predominant component of the connective tissue.
STRUCTURE OF COLLAGEN
  • In principle, all types of collagen are triple helical structures.
  1. The collagen triple helix structure is not found free in Cytoplasm.
  • The amino acid composition of collagen is unique.
  • Approximately 1/3rd of the amino acids are contributed by glycine i.e. every third amino acid in collagen is glycine. Hence, the repetitive amino acid sequence of collagen is represented by (GIy-X-Y)n, where X and Y represent other amino acids. Among the other amino acids, proline and hydroxyproline are present in large quantities . These two amino acids confer rigidity to the collagen molecule.
  • The triple helical structure of collagen is stabilized by an extensive network of hydrogen bonds, covalent cross-links, electrostatic and hydrophobic interactions, and van der Waals forces.
  •  Dense collagen is found in Aponeurosis , Ligament ,Tendon.
BIOSYNTHESIS OF COLLAGEN
Inside fibroblasts :

  • pre-pro-collagen α chain formation
  1. RER-bound ribosomes synthesize
  2. contains hydrophobic translocation sequence
  3. 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.
  • performed by prolyl and lysyl hydroxylase. 
  • Hydroxylation of peptidyl prolyl residues in collagen require Ascorbate , α ketoglutarate , Oxygen , Fe2+ ,Dioxygenases.
  1. glycosylated pro-collagen α chain formation :hydroxylysines are glycosylated
  2. pro-collagen α chain trimer formation
  • moved from RER to Golgi and then secreted out of the fibroblast
Outside fibroblasts :
collagen molecule (tropocollagen) formation

  • propeptides cleaved from ends and becomes insoluble
  • The 40 nm gap in between the tropocollagen molecule in collagen which serve as the site of bone formation is occupied by Calcium.
collagen fibril formation
  • catalyzed by lysyl oxidase
  • covalently links α chains by crosslinking hydroxylysines
  • copper required as cofactor
  • lack of copper results from Menke’s disease
collagen fiber formation
  • fibrils aggregate to form final bundles of triple helix quaternary protein structure
TYPE OF COLLAGEN AND LOCATION
  • I Bone (most abundant form)
  • II Cartilage, vitreous tumour, Intervertebral disc
  • III Extensive - skin, lung, hollow organ (vascular system)
  • IV Basement membrane, Eye lens
  • VII Anchoring fibrils at Dermo-epidermal junction
  • VIII Endothelium
  • X Hypertrophic cartilage
  • XVII Skin, hemidesmosomes
  • XVIII Liver, kidney
  • XIX Rhabdomyasarcoma cells
ABNORMALITIES ASSOCIATED WITH COLLAGEN
  • Ehlers -Danlos Syndrome occurs due to Mutations in collagen genes and Lysyl hydroxylase gene, characterized by hyperextensibility of skin, and abnormal tissue fragility.
  • Alport syndrome-due to a defect in the formation of type lV collagen fibres found in the basement membrane of renal glomeruli.
  • Osteogenesis imperfecta-characterized by abnormal fragility of bones due to abnormality in Collagen type I
  • Epidermolysis bullosa-due to alteration in the structure of type Vll collagen. The victims exhibit skin breaks and blisters formation even for a minor trauma.
  • Scurvy
COLLAGEN AND WOUND HEALING
  • Maximum collagen in wound healing is seen at end of second week.
  • Complete wound strength in terms of collagen recovery is never regained.
  • Keloid scar is made up of dense Collagen.
  • Strength of wound after 2 months is governed by Collagen cross linking.
Exam Question of:
  • Collagen is not found in fibroblasts.
  • Complete wound strength in terms of collagen recovery is never regained .
  • Type IV of collagen is predominant in basement membrane.
  • Vitamin C is required in proper synthesis of collagen.
  • Type I is the predominant collagen type in bone .
  • Hydroxylation of peptidyl prolyl residues in collagen require Ascorbate , α ketoglutarate , Oxygen , Fe2+ ,Dioxygenases.
  • The collagen triple helix structure is not found free in Cytoplasm.
  • Osteogenesis imperfecta is a group of diseases characterized by genetic mutations which lead to Shortened a1(I) collagen chains.
  • Collagen is Triple helix structure.
  • Intracellular events occuring in fibroblast during synthesis of collagen : Formation of triple helix.
  • The 40 nm gap in between the tropocollagen molecule in collagen which serve as the site of bone formation is occupied by Calcium.
  • Type of collagen forming basement membrane of kidney is type IV.
  • Defect in collagen formation is seen in Scurvy, Osteogenesis imperfecta, Ehler - Danlos syndrome & Alport syndrome.
  • Articular cartilage is made up of type II collagen.
  • Maximum collagen in wound healing is seen at end of second week.
  • Highest concentration of hydroxy proline is seen in Collagen. In congenital dystrophic epidermolysis bullosa defect is seen in Collagen type VII.
  • Keloid scar is made up of dense Collagen.
  • Mutation in alpha 5 chain of collagen 4 causes Alport's syndrome.
  • Tensile strength of wound after laparoscopic cholecystectomy in a 30 years old woman depends upon extensive crosslinking of tropocollagen.
  • Type of collagen present in cornea is Type I.
  • Strength of wound after 2 months is governed by Collagen cross linking.
  • Major protein of bone is Collagen type I.
  • Sequence of amino acid in collagen is Gly-X-Y.
  • Vitreous humor contains type II of collagen.
  • Ehlers -Danlos Syndrome occurs due to Mutations in collagen genes and Lysyl hydroxylase gene.
  • Dense collagen is found in Aponeurosis , Ligament ,Tendon.
  • Components of collagen : Glycine, lysine, proline.
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