Collagen structure and synthesis
Dr. Atif Hassan KhirelsiedDr. Atif Hassan Khirelsied
Department of BiochemistryFaculty of Medicine
International University of Africa
CollagenCollagen
Collagen is insoluble fibrous protein.
Collagen Collagen
g p
Mainly found in the extracellular matrix and in connective
tissuetissue.
The most abundant protein in mammals (>25% of body
proteins)proteins).
Has great tensile strength, in ligaments and tendons.
CollagenCollagenCollagen Collagen
Is responsible for skin elasticity, and its degradation leads
to wrinkles that accompany aging.p y g g
Fills out the cornea where it is present in crystalline form.
Also used in cosmetic surgery, e.g., lip enhancement.
CollagenCollagen
• There are at least 16 types of collagen 90% percent of
Collagen Collagen
• There are at least 16 types of collagen, 90% percent of the collagen in the body consists of types I, II, and III
The most abundant types of collagen
CollagenCollagenType Representative Tissues
Collagen Collagen
Fibrillar collagens I Skin, tendon, bone, ligaments, dentin, interstitial
tissuestissuesII Cartilage, vitreous humorIII Skin, muscle, blood vesselsV Similar to type I; also cell cultures, fetal tissues
Fibril‐associated collagensFibril associated collagensVI Most interstitial tissues
IX Cartilage vitreous humor;IX Cartilage, vitreous humor;
Sheet forming collagensSheet‐forming collagensIV All basal laminaes
Collagen componentsCollagen componentsCollagen components Collagen components
•Insoluble glycoprotein (protein + carbohydrate)
Protein
•High glycine and two modified amino acids hydroxylysine,
hydroxyproline (gly‐X‐Y)n.
Carbohydrate (glucose , galactose )
Collagen structure Collagen structure
Collagen is a
fibrous protein built p
up of three α‐
chains(not α‐helices)
which form a rope‐p
like triple helix.
Collagen structureCollagen structureCollagen structure Collagen structure
Collagen has an unusual
amino acid compositionamino acid composition,
every α‐chain consists of a
repeating triplet (Gly‐X‐Y).
Collagen structureCollagen structure
Th l i i ll h fi i h f h
Collagen structure Collagen structure
The glycine is small enough to fit into the center of the
triple helix. p
In addition to the glycine collagen contains (proline,
hydroxyproline and hydroxylysine).hydroxyproline and hydroxylysine).
These later amino acids results from post translational
modificationmodification.
Collagen structureCollagen structureCollagen structure Collagen structure
Proline is found in the X position and 4‐hydroxyproline in
the Y position.
The hydrogen‐bonding stabilizes the triple helix.
Collagen structureCollagen structureCollagen structure Collagen structure
Interchain hydrogen bonding in collagen. The amide hydrogen of a glycine residue in one chain is hydrogen‐bonded to the carbonyla glycine residue in one chain is hydrogen‐bonded to the carbonyl oxygen of a residue, often proline, in an adjacent chain.
Collagen structure Collagen structure
Covalent cross‐links in collagen. (a) An allysine residue condenses with a lysine residue to form an intermolecular Schiff‐base crosslink. (b) Two allysine residues condense to form an intramolecular aldol cross‐link.
Collagen structureCollagen structure
•Type I collagen is the most common fibrillar collagen (90%),
Collagen structure Collagen structure
and is found in bone, skin, tendons, vascular, ligature, organs,.
•Type II collagen provides similar tensile strength to cartilage.
C ll T III i l fib i h I•Collagen Type III ‐ reticular fibers with type I.
•Type IV and VII collagens are network‐forming collagens; they
f h k i l l i b l l iform a meshwork, particularly in basal lamina.
Collagen disordersCollagen disordersCollagen disorders Collagen disorders
Collagen Diseases ‐ Excess
1. Fibrosis.
2 L l fib i2. Lung‐ pulmonary fibrosis.
3. Liver‐ over consumption of alcohol.
4. Arteries‐ atherosclerosis.
Collagen disordersCollagen disordersCollagen disorders Collagen disorders
Collagen Diseases – Insufficient
1 Scurvy1. Scurvy
2. Ehlers‐Danlos syndrome (rubber‐man)
3. Osteogenesis imperfecta
d ( )4. Atopic dermatitis (AD)
Scurvy
1 Dietary vitamin C deficiency
Scurvy
1. Dietary vitamin C deficiency
2. Needed for hydroxylation of proline and lysine.
3. Form too few hydrogen bonds in collagen.
4. Skin, bone, teeth weakness and malformation .
5 Blood vessels weakened bleeding5. Blood vessels weakened, bleeding.
Scurvy symptomsScurvy symptoms
1. Malaise and lethargy and bone pain
2. Skin changes with roughness, easy
b i i d t hibruising and petechiae.
3. Gum disease, loosening of teeth, , g ,
4. Poor wound healing, and emotional
changes.
Ehlers Danlos Syndrome
•Also knwon as rubber man disease
Ehlers Danlos Syndrome
•Also knwon as rubber‐man disease
•Skin and tendons easily stretched
Characterized by; y;
1. loose joints.
2. Elastic skin," "India rubber
skinskin
Osteogenesis imperfectaOsteogenesis imperfecta
1. Brittle‐bone syndrome
2 Mutation in Type I procollagen2. Mutation in Type I procollagen
3. Fail to assemble triple helix
4. Degrade imperfect collagen
5. Leads to fragile bones