COLLAGEN

1. COLLAGEN & ITS
SYNTHESIS
DR SAKINA ,MBBS,M.D
SENIOR LECTURER ,MSU

2. COLLAGEN

3. 1.Definition
2.Basic information of collagen
3.Different Types of collagen
4.Molecular Structure
5.synthesis of collagen
6.Functions of collagen
6.Abnormalities associated with Collagen

4. 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

5. 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- Tendons
3. Stacked- as in Cornea
4. Fibers arranged at an angle- Bones

6. 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 6

7. 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.

8.  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.

9. STRUCTURE OF COLLAGEN
 Collagen has a most unusual amino acid composition in
which Glycine, Proline, Hydroxyproline, Lysine &
Hydroxylysine are dominant.
Glycine

10. Proline
3-Hydroxyproline 4-Hydroxyproline

11. NH2
|
NH2 – CH2 – CH – CH2 – CH2 - C – H
|
COOHLysine
5-Hydroxylysine

12. 12

13.  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.

14.  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.

15. SYNTHESIS OF COLLAGEN

16. SYNTHESIS OF COLLAGEN
Precursors:
 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.

17. 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

18. 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).

19. N CH
CH2
CH2
CH2
O
N CH
CH2
CH2
CH
O
OH
NH3
+
CH2
CH2
CH2
CH2
CHNH
O
NH3
+
CH2
CH
CH2
CH2
CHNH
O
OH
-ketogutarate succinate
-ketogutarate succinate
prolyl hydroxylase
lysyl hydroxylase
(ascorbate)
(ascorbate)
O2 + CO2 +
O2 + CO2 +
proline
4-hydroxyproline
lysine 5-hydroxylysine

20. galactosyl
transferase
glucosyl
transferase
UDP-galactose UDP-glucose
NH3
+
CH2
CH
CH2
CH2
CHNH
O
OH
O
CH2
O
OH
OH
OH
OH
H
H
H H
H
O
CH2
O
O
OH
OH
OH
H
H
H
H
H
CH
CH2
CH2
CH2
CH
NH3
+
NH
O
3. Glycosylation:
Modified by glycosylation with glucose or
galactose residues

21. 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.

22.  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.

23.  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

24. 6. Formation of collagen fibrils:
Tropocollagen spontaneously
associate with each other and form
collagen fibrils

25. 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

26.  These covalent bonds cross-link gives the fiber exceptional
strength and rigidity.

28. 28

29. 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

30. FUNCTIONS OF COLLAGEN
1.To give support to organs
2.To provide alignment of cells
3.In blood vessels if collagen is
exposed,platelets adhere and
thrombus formation is initiated
30

31. 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)

32. ABNORMALITIES ASSOCIATED WITH
COLLAGEN
EHLERS-DANLOS SYNDROME
- group of inherited disease
- collagen involved type III-
- defective lysyl oxidase
Characteristics
- hyper extensibility of skin.
- abnormal tissue fragility
-increase joint mobility

34. ALPORT SYNDROME
 Collagen involved- type IV (found in the basement
membrane of glomerulus)
Characteristics-
- Hematuria
- renal diseases

35. OSTEOGENESIS IMPERFECTA
Caused due to abnormal (less) Collagen type I
Characteristics
- weak bones
- fragile bones

37. EPIDERMOLYSIS BULLOSA
Due to alteration of Collagen type VII
Characteristics
- skin breaks
- blister formation

39. 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