Download - 3.sakina collagen
Objectives
1.Definition2.Basic information of
collagen3.Different Types of collagen4.Molecular Structure 5.synthesis of collagen6.Functions of collagen6.Abnormalities associated
with Collagen
DEFINITION Derived from Greek word “kolla”
meaning Glue Producer” Major structural protein found in
connective tissue Is collagen
It is a fibrous element of tissues like bone teeth,tendon,cartilage &blood vessel
It Yield gelatin and glue upon boiling with water
BASIC INFORMATION ABOUT COLLAGEN
It is long, rigid structure in which three polypeptides are wound around one another in a rope like fashion.
These polypeptides are called α-helix Example:1. Gel- extracellular matrix or vitreous humor
of eye.2. Tight bundles- Tendons3. Stacked- as in Cornea4. Fibers arranged at an angle- Bones
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COLLAGEN
Organised into 3 groups based on location & function in the body
1.FIBRIL FORMING COLLAGEN – include type I,II,III
2.NETWORK FORMING COLLAGEN-include type IV ,VII
3.FIBRIL ASSOCIATED COLLAGEN – include type IX ,XII
DIFFERENT TYPES OF COLLAGEN
•This classification is taken from Harper’s illustrated biochemistry-27th edition which describes 19 different types. •As per latest research 29 types of collagen have been found.•Over 90% of the collagen in the body, however, are of type I, II, III, and IV.
The types of collagen are designated by Roman numerals.
Constituent procollagen chains, called pro α chain For instance, Type I procollagen is assembled
from two pro α 1 (I) and one pro α 2 (I) chain. It is thus a heterotrimer.
Whereas Type 2 procollagen is assembled
from three pro α 1 chains and is thus a homotrimer.
STRUCTURE OF COLLAGEN Collagen has a most unusual amino acid
composition in which Glycine, Proline, Hydroxyproline, Lysine & Hydroxylysine are dominant.
Glycine
These amino acids are arranged in a repetitious tripeptide sequence, Gly-X-Y, in which X can be any amino acid but is frequently a Proline and Y is frequently a Hydroxyproline or Hydroxylysine.
Individual collagen polypeptide chains (each with about 1000 amino acid residues) assume a left-handed helical conformation (with 3 amino acids per turn) and aggregate into 3 stranded cables with a right-handed twist.
The Glycine at every third residue is required because there is no room for any other amino acid inside the triple helix where the glycine R-group is located.
SYNTHESIS OF COLLAGENPrecursors: Collagen is one of the proteins that
functions outside the cell.
Polypeptide Precursors of the collagen molecule are formed in Fibroblast, osteoblasts and chondroblasts.
These are secreted into the extracellular matrix.
1.Formation of Pro- α-chains: Pre-pro α-chains- contain a special amino acid sequence at their
N-terminal.This sequence acts as a signal peptide
This sequence facilitate the binding of ribosomes to the rough endoplasmic reticulum (RER), and direct the Pre-pro α-chain into the lumen of the RER
This sequence is cleaved in the lumen of RER and after its cleavage Precursor of collagen is formed.
This precursor is called Pro α-chain
2. Hydroxylation: Processing of Pro α-chains occur by a number of
enzymic steps in the lumen of RER.
Proline and lysine residues are hydroxylated intracellularly by prolyl & lysyl hydroxylase,(contain ferrous iron at active site) O2 and vitamin C
It is a post translational modification
Vit C deficiency, Leads to poor hydroxylation- and tensile strength is decreased (scurvy).
N CH
CH2CH2
CH2
ON CH
CH2CH2
CH
O
OH
NH3
+
CH2CH2
CH2
CH2
CHNHO
NH3
+
CH2CH
CH2
CH2
CHNHO
OH
-ketogutarate succinate
-ketogutarate succinate
prolyl hydroxylase
lysyl hydroxylase
(ascorbate)
(ascorbate)
O2 + CO2 +
O2 + CO2 +
proline4-hydroxyproline
lysine 5-hydroxylysine
galactosyl transferase
glucosyltransferase
UDP-galactose UDP-glucoseNH3
+
CH2CH
CH2
CH2
CHNHO
OH
OCH2
O
OHOH
OH
OH
H
H
H HH
OCH2
O
O
OH
OH
OH
H
HH
H
H
CH
CH2
CH2
CH2
CH
NH3+
NH
O
3. Glycosylation: Modified by glycosylation with glucose or
galactose residues
4. Assembly and Secretion: After hydroxylation and glycosylation- Pro α-chains are
converted to Pro-collagen. Pro-collagen has a central region of triple helix and its ends have
non-helical regions of amino and carboxyl terminal extensions . These extensions are called Propeptides.
In the formation of procollagen interchain disulfide bonds are formed between the C- terminal extensions of the pro α-chains.
This alignment of pro α-
chains is favorable for helix formation.
Then pro-collagen chains are
translocated to Golgi- apparatus.
In the golgi apparatus they are packaged in secretory vesicles.
These vesicles fuse with the membrane and release the pro-collagen molecule into the extracellular space.
5. Extracellular cleavage of Procollagen molecules:
After their release, The Procollagen molecules are cleaved by N- and C- Procollagen peptidases.
These remove the terminal Propeptides.
Triple helical structure is released as Tropocollagen
6. Formation of collagen fibrils:Tropocollagen spontaneously
associate with each other and form collagen fibrils
7. Cross-link formation: The collagen fibres are strengthened by
covalent cross link between lysine & hydroxylysine residues by lysyl oxydase which converts these amino acid into Aldehyde ,which form into Aldol condensation near amino terminal
This enzyme contain copper at its active site,In copper deficiency collagen synthesis is Abnormal
Degradation of collagen: Collagen highly stable molecule. Half life is several years. Breakdown- collagenases
Degradation of collagen is seen when there is bone and cartilage resorption, osteoporosis,tumour metastasis,paget’s disease,rickets,osteoarthritis etc
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FUNCTIONS OF COLLAGEN
1.To give support to organs2.To provide alignment of cells3.In blood vessels if collagen is
exposed,platelets adhere and thrombus formation is initiated
Medical uses:- Collagens are widely employed in the construction
of artificial skin substitutes used in the management of severe burns & beauty treatments.
(These collagens may be derived from bovine, equine or porcine, and even human sources and are sometimes used in combination with silicones, glycosaminoglycans, fibroblasts, growth factors and other substances)
ABNORMALITIES ASSOCIATED WITH COLLAGENEHLERS-DANLOS SYNDROME - group of inherited disease - collagen involved type III- - defective lysyl oxidase
Characteristics - hyper extensibility of skin. - abnormal tissue fragility -increase joint mobility
ALPORT SYNDROME
Collagen involved- type IV (found in the basement membrane of glomerulus)
Characteristics- - Hematuria - renal diseases
OSTEOGENESIS IMPERFECTACaused due to abnormal (less) Collagen type I
Characteristics - weak bones - fragile bones
EPIDERMOLYSIS BULLOSADue to alteration of Collagen type VII
Characteristics - skin breaks - blister formation
SCURVY Gly –X- Y (Y = 4-hydroxyproline)
Enzyme : propyl-4-hydroxylase
Co-factor: Vit. C. Due to Vit C deficiency(impaired synthesis of collagen due to
deficiencies of prolyl and lysyl hydroxylases)Characteristics- - bleeding gum - delayed wound healing