5. Introduction
Collagen is protein molecules made up of
amino acids. It provides structural support to
the extracellular space of connective tissues.
Location
Collagen is principal protein of the skin,
tendons, ligaments, cartilage, bone, and
connective tissue.
6. Types of Collagen
Some 28 types of collagen types have been identified.
They differ by:
how the molecules are assembled,
the cell components that are added
where the collagen is used in your body.
7. Types of Collagen
The main five types of collagen and what they do are:
Type l. This type makes up 90% of your body’s collagen. …
Type II. This type is found in elastic cartilage, which provides
joint support.
Type III. This type is found in muscles, arteries and organs.
Type IV. This type is found in the layers of your skin.
Type V.collagen contributes to the bone matrix, corneal
stroma, and the interstitial matrix of muscles, liver, lungs, and
placenta
8. Structure of collagen
A typical collagen molecule is a long,
rigid structure in which three polypeptides
(referred to as “α chains”) arewound around
one another in a rope-like triple helix
Triple-helical structure:
Collagen, a fibrous protein, has an
elongated, triple-helical structure that
places many of its amino acid side chains
on the surface of the triple-helical
molecule.
9. Biosynthesis of Collagen
The main steps in collagen biosynthesis are
transcription and translation,
hydroxylations of prolyl and lysyl residues,
glycosylations of hydroxylysyl residues,
chain association and disulphide bonding,
triple helix formation,
secretion of procollagen into the extracellular matrix,
conversion of procollagen into collagen
10. Cellular level
Intracellular
Transcription of mRNA in the nucleus
Genes for pro-a1 and pro-a2 chains are transcribed
Translation
mRNA moves into the cytoplasm and interacts with ribosomes for
translation.
After translation, it is referred to as pre-pro-polypeptide chain; this
chain then travels to the endoplasmic reticulum (ER) for post-
translational modification.
11. Intracellular level
Post-translational modification
Once in the ER, the pre-pro-polypeptide undergoes post-translational
processing where three major modifications are made to the pre-pro-
polypeptide for it to become pro-collagen.
The signal peptide on the N-terminal is removed
The lysine and proline residues get additional hydroxyl groups added to
them via hydroxylase enzymes which require vitamin C as a cofactor
Glycosylation of the selected hydroxyl groups on lysine with galactose
and glucose
12. Intracellular level
Three of the hydroxylated and glycosylated pro-a-
chains assemble by twisting into a triple helix by zipper-
like folding. The triple helix configuration is 3 left-handed
helices twisted into a right-handed coil
Now the pro-collagen molecule is ready to move to the
Golgi apparatus for final modifications and assembled
into secretory vesicles to enter the extracellular space
13. Extracellular
Propeptide cleavage
Enzymes known as collagen peptidases preform
propeptide cleavage and remove the ends of the
procollagen molecule and the molecule becomes
tropocollagen
Collagen Fibril Assembly
Lysyl oxidase a copper-dependent enzyme acts on
lysine and hydroxylysines, and covalent bonding
between tropocollagen molecules form a collagen fibril
14. Collagen Disease
Defects in any one of the many steps in collagen fiber
synthesis can result in a genetic disease involving,
an inability of collagen to form fibers properly and, thus,
provide tissues with the needed tensile strength
normally provided by collagen
More than 1,000 mutations have been identified in 22
genes coding for twelve of the collagen types.
15. Ehlers-Danlos syndrome
This disorder is a heterogeneous group of generalized connective tissue
disorders.
EDS can result from a deficiency of collagen-processing enzymes.
The most clinically important mutations are found in the gene for type III
collagen.
Because collagen type III is an important component of the arteries,
potentially lethal vascular problems occur.
Clinical features are hyperextensibility of skin, abnormal tissue fragility and
increased joint mobility
16. Ehlers Danlos Syndrome
Type IV is most serious
because of spontaneous
rupture of arteries
Type IV is due to deficiency
of lysyl hydroxylase
Strechy skin due to ehler
denlos syndrome
17. Marfan Syndrome
An inherited condition
characterized particularly by
skeletal changes (elongation of the
limbs and digits and looseness of
joints), displacement of the lens of
the eye, and a tendency to
develop aneurysms, especially of
the aorta.
18. Osteogenesis imperfecta
This disease, known as brittle bone syndrome, is also a
heterogeneous group of inherited disorders
distinguished by bones that easily bend and fracture.
osteogenesis imperfecta tarda
osteogenesis imperfecta congenita
The most common mutations cause the replacement
of glycine residues (in –Gly–X–Y–) by amino acids with
bulky side chains. The resultant structurally abnormal
pro-α chains prevent the formation of the required
triple-helical conformation.
19. Types of osteogenesis imperfecta
Type l. Mildest and most common type. About 50% of all
affected children have this type. There are few fractures and
deformities
Type II. Most severe type. A baby has very short arms and legs,
a small chest, and soft skull. He or she may be born with
fractured bones. He or she may also have a low birth weight
and lungs that are not well developed. A baby with type II OI
usually dies within weeks of birth
20. Types of osteogenesis imperfecta
Type III.Most severe type. A baby has very short
arms and legs, a small chest, and soft skull. He or
she may be born with fractured bones. He or she
may also have a low birth weight and lungs that
are not well developed. A baby with type II OI
usually dies within weeks of birth
21. Types of osteogenesis imperfecta
Type 4. Symptoms are between mild and severe. A
baby with type IV may be diagnosed at birth. He or she
may not have any fractures until crawling or walking.
The bones of the arms and legs may not be straight. He
or she may not grow normally.
Type 5. Similar to type IV. Symptoms may be medium to
severe. It is common to have enlarged thickened areas
(hypertrophic calluses) in the areas where large bones
are fractured
22. Types of osteogenesis imperfecta
Type VI. Very rare. Symptoms are medium. Similar to
type IV.
Type VII. May be like type IV or type II. It is common to
have shorter than normal height. Also common to have
shorter than normal upper arm and thighbones.
Type VIII. Similar to types II and III. Very soft bones and
severe growth problems.
