3. Types of CollagenTypes of Collagen
• The collagen super family of proteins includes more than 25
collagen (approximately 28) types, as well as additional proteins that
have collagen-like domains.
• Variations in the amino acid sequence of the α chains result in
structural components that are about the same size (approximately
1,000 amino acids long), but with slightly different properties.
4. Types of CollagenTypes of Collagen
• These α chains are combined to form the various types of collagen
found in the tissues. For example, the most common collagen, type
I, contains two chains called α1 and one chain called α2 (α12α2),
whereas type II collagen contains three α1 chains (α13).
• The collagens can be organized into three groups, based on their
location and functions in the body
5.
6.
7. Structure of collagen
• Amino acid sequence:
• Collagen is rich in proline and glycine, both of which are important
in the formation of the triple-stranded helix.
• Proline facilitates the formation of the helical conformation of each α
chain because its ring structure causes “kinks” in the peptide chain.
8. Structure of collagen
• Glycine, the smallest amino acid, is found in every third position of
the polypeptide chain. It fits into the restricted spaces where the
three chains of the helix come together.
• The glycine residues are part of a repeating sequence, –Gly–X–Y–,
where X is frequently proline and Y is often hydroxyproline (but can
be hydroxylysine).
9. Triple-helical structure
• Unlike most globular proteins that are folded into
compact structures, collagen has an elongated, triple-
helical structure that places many of its amino acid side
chains on the surface of the triple-helical molecule.
10.
11. Hydroxyproline and Hydroxylysine
• Collagen contains hydroxyproline (hyp) and hydroxylysine (hyl),
which are not present in most other proteins.
• These residues result from the hydroxylation of some of the proline
and lysine residues after their incorporation into polypeptide chains
(post translational modification)
.
12.
13. Glycosylation
• The hydroxyl group of the hydroxylysine residues of
collagen may be enzymatically glycosylated.
• Most commonly, glucose and galactose are sequentially
attached to the poly - peptide chain prior to triple-helix
formation
14.
15. Biosynthesis of collagen
• The polypeptide precursors of the collagen molecule are
formed in fibroblasts (or in the related osteoblasts of
bone and chondroblasts of cartilage), and are secreted
into the extracellular matrix.
• After enzymic modification, the mature collagen
monomers aggregate and become cross-linked to form
collagen fibers.
24. Degradation of collagen
• Normal collagens are highly stable molecules, having
half-lives asnlong as several years.
• However, connective tissue is dynamic and is constantly
being remodeled, often in response to growth or injury of
the tissue.
25. Degradation of collagen
• Breakdown of collagen fibers is dependent on the proteolytic action
of collagenases, which are part of a large family of matrix
metalloproteinases.
28. Scurvy
• A disease resulting from a deficiency of vitamin C, which
is required for the synthesis of collagen in humans.
• Scurvy often presents itself initially as symptoms of
malaise and lethargy, followed by formation of spots on
the skin, spongy gums, and bleeding from the mucous
membranes.
29. Scurvy
• In ascorbic acid deficiency (and, therefore, a lack of prolyl
and lysyl hydroxylation), interchain H-bond formation is
impaired, as is formation of a stable triple helix.
• Additionally, collagen fibrils cannot be cross-linked (see
below), greatly decreasing the tensile strength of the
assembled fiber. Patients with scurvy also often show
bruises on the limbs as a result of subcutaneous
extravasation of blood due to capillary fragility
30.
31. Ehlers-Danlos Syndrome (EDS)
• This disorder is a group of generalized connective tissue
disorders that result from inheritable defects in the
metabolism of fibrillar collagen molecules.
• It is a group of inherited disorders that affect your
connective tissues — primarily your skin, joints and
blood vessel walls.
32. Ehlers-Danlos Syndrome (EDS)
• EDS can result from a deficiency of collagen-processing
enzymes (for example, lysyl hydroxylase or procollagen
peptidase), or from mutations in the amino acid
sequences of collagen types I, III, or V.
33. Ehlers-Danlos Syndrome (EDS)
• The most clinically important mutations are found in the
gene for type III collagen.
• Collagen containing mutant chains is not secreted, and
is either degraded or accumulated to high levels in
intracellular compartments.
• Because collagen type III is an important component of
the arteries, potentially lethal vascular problems occur.
34.
35. Osteogenesis Imperfecta (OI)
• This disease, known as brittle bone syndrome, is a
group of inherited disorders distinguished by bones that
easily bend and fracture.
• They are around eight (8) types of OI but type 1 is the
most common
36. • Most patients with severe OI have mutations in the gene
for either the pro-α1 or pro-α2 chains of type I collagen.
• 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.
37. • Type I OI is called osteogenesis imperfecta tarda. The
disease is the consequence of decreased production of
α1 and α2 chains.
• It presents in early infancy with fractures secondary to
minor trauma, and may be suspected if prenatal
ultrasound detects bowing or fractures of long bones.
• Type II OI is called osteogenesis imperfecta congenita,
and is the most severe. Patients die of pulmonary
hypoplasia in utero or during the neonatal period.
41. Cowan, R., Gaw, A., Murphy, M., & O'Reilly, D. S. (2013).
Clinical Biochemistry, 5th Edition. USA: Churchill
LivingstoneElsevier.
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