The document discusses the significance of collagen, a connective tissue protein crucial for various body functions, including development, inflammation, and aging. It outlines the types, structure, biosynthesis, and disorders related to collagen, such as Ehlers-Danlos syndrome and osteogenesis imperfecta, which arise from genetic defects or nutritional deficiencies. Additionally, the document highlights the medical and industrial applications of collagen, including its use in cosmetic surgery, food products, and pharmaceuticals.

1. Collagen
The connective tissue protein

2. Why study tissue proteins?
 To understand normal body functions .
 In development
 In inflammatory states
 Aging process.
 To identify the cause of various genetic and metabolic disorders related
to tissue proteins
 In the spread of cancer cells.
 Several diseases (eg:Osteogenesis imperfecta and a number of
types of the Ehlers-Danlos syndrome) are due to genetic
disturbances of the synthesis of collagen.
 Components of proteoglycans are affected in the group of genetic
disorders known as the mucopolysaccharidoses.
 To use and apply them in the medical, industrial, commercial fields.
 In food products, cosmetic surgery.
 The gelatin used in food and industry is derived from the partial
hydrolysis of collagen.

3. The Extracellular Matrix
 The space outside the cells of a tissue is filled with a composite material
called extracellular matrix(ECM).
 This ECM is also known as the connective tissue. It is composed of -
a) Gel with interstitial fluid.
b) 3 major classes of biomolecules:
 Structural proteins: collagen, elastin and Keratin(epidermal tissues)
 Specialized proteins: e.g. fibrillin, fibronectin, and laminin.
 Proteoglycans(Mucoproteins) : Conjugated proteins consisting of
 Protein + Carbohydrate(5%-95%)
 Carbohydrate part is in the form of Glycosaminoglycans [GAGs].
 Thus, the extracellular matrix (ECM) is a complex structural entity
surrounding and supporting cells that are found within mammalian tissues.

4. The Extra cellular matrix

5. Collagen
 Most abundant insoluble fibrous protein in
the connective tissue of mammals.
 Makes up about 25% to 35% of the
whole-body protein content.
 Scleroprotein secreted from the cells
called fibroblasts.
 In greek ‘kolla’ means ‘glue’.Collagen is
also called as glue-producer.
 Distribution of collagen varies in different
tissues.
 Also found in mucous membranes,
nerves,Blood vessels, and organs.
90%
85%
70%
4%
bones tendons
skin liver
Collagen fibers in
muscle tendons

6. Functions Of Collagen
 It imparts strength, support, shape
and elasicity to the tissues.
 It accounts for 6% of the weight
of strong, tendinous muscles
 It provides flexibility, support, and
movement to cartilage.
 It encases and protects delicate
organs like kidneys and spleen.
 It fills the sclera of the eye in
crystalline form.
 Teeth(dentin) are made by adding
mineral crystals to collagen.
 Collagen contributes to proper
alignment of cells for cell
proliferation and differentiation.
 When exposed in damaged blood
vessels, it initiates thrombus
formation

7. Types Of Collagen
 In humans, there are at least 19
distinct types of collagen made up
of 30 distinct polypeptide chains
(each encoded by a separate
gene).
 They are subdivided into a number
of classes based primarily on the
structures they form
 However, 90% of the collagen in
the body are of type I, II, III, and IV.
 These types determine the physical
properties of specific tissues and
perform their specialized function.

8. Structure Of Collagen
The basic structural unit of a
collagen molecule is a triple helix.
Triple helical structure may occur
throughout the molecule or only in a
part of it.
Structure Of type I mature
Collagen:
 Triple helical structure occurs
throughout the molecule.
 This triple helix is composed
of 3 polypeptide chains twisted
around each other.
 Each polypeptide/alpha chain
is in turn a left handed helix with
3 amino acids per turn totally
containing approximately 1000
amino acids per chain.
Alpha chain Triple Helix
Amino-
acids

9. Each alpha chain has an unusual
abundance of 3 amino-acids
glycine, proline and hydroxyproline.
 Glycine occurs at every third
position in the amino acid sequence
which can be represented as (Gly-X-
Y)n.
 X and Y are other amino acids of
which proline and hydroxyproline
occupy 100 positions each.
 Glycine occupies the crowded
center of the triple helix as it has a
small side chain[ H atom] where as
Hydroxyproline and proline point
outwards imparting rigidity to the triple
helix.
 The alpha chains are wound
around each other in a right handed
super helix to form a rod like molecule
1.4nm wide and 300nm long
[Gly-X-Y]n

10. The triple helices are stabilized by
Hydrogen bonds, covalent cross-
links, electrostatic and hydrophobic
interactions and van der waals forces.
The covalent cross links within and
between the helices are formed by
copper dependent enzyme lysyl
oxidase between the lysine and
hydroxylysine residues.
These triple helical molecules pack together
side by side to form elongated fibrils.
Fibrils are displaced longitudinally from each
other by 67 nm [one quatter of its length] to form
a quarter staggered arrangement.
Fibrils bundle up to form fibers making up
tissues.
Cross link formation

11. Structure of collagen fibers

12. Biosynthesis of Collagen
 Collagen synthesis occurs in the fibroblasts, osteoblasts in
bone, chondroblasts in cartilage and odontoblasts in teeth.
 First synthesized in precursor form of preprocollagen polypeptide chain
in the ribosomes during translation
 The leader sequence of amino acids[signal peptide] in the
preprocollagen directs it to enter the lumen of E.R
 In the lumen of E.R, the Signal peptide is cleaved to form procollagen.
 The proline and lysine amino acids in the procollagen chain undergo
hydroxylation and glycosylation known as post translational
modifications.
 Disulfide bonds are formed between three procollagen chains which
twist around each other to form a triple helix molecule.This step is called
registration.
 This Procollagen molecule is secreted into the extracellular matrix from
the golgi compartment of the E.R.
 Here, the procollagen aminoproteinase and carboxy proteinase
enzymes remove extra terminal amino acids from the procollagen
molecule to form collagen .
 The collagen molecules assemble into fibrils and inturn fibers being stabilized
by the covalent cross-links.

13. Biosynthesis of
collagen from
Preprocollagen

14. Synthesis Of Collagen

15. Abnormalities associated with collagen
 Collagen-related diseases arise from
 genetic defects
 nutritional deficiencies
 They affect the biosynthesis, assembly, postranslational modification, secretion, or
other processes involved in normal collagen production.
 These include :
 Ehler Danlos syndrome
 Alport syndrome
 Epidermolysis bullosa
 Osteogenesis Imperfecta
 Chondrodysplasias [affects cartilage]
 Scurvy
 Osteolathyrism

16. Ehler Danlos Syndrome
 Ehlers-Danlos Syndrome is a group of inherited connective tissue disorders.
 CAUSE
 abnormalities in the synthesis and metabolism of collagen
 Mutations in the collagen genes: COL1A1, COL1A2, COL3A1, COL5A1, COL5A2
 a deficiency of enzyme lysyl hydroxylase.
 A deficiency of procollagenN-proteinase, causing formation of abnormal
thin, irregular collagen fibrils
 EFFECT
 Mutations alter the structure, production, or processing of collagen or proteins
that interact with collagen
 WeakenS connective tissue in the skin, bones, blood vessels, and organs causing-
 Skin hyperextensibility
 Joint dislocations
 Tissue fragility
 Poor wound healing.

17. Ehler-Danlos
Syndrome
•Hyperextensibility of
skin
•Hypermobility of
joints

18. Alport Syndrome
 Alport syndrome is a genetic disorder
characterized by
glomerulonephritis, endstage kidney
disease, and hearing loss.
 It also affects the eyes.
 The presence of blood in the
urine[hematuria] is almost always found
in this condition.
 CAUSE
 Mutations in COL4A3,COL4A4,COL4A5
collagen biosynthesis genes.
 These prevent the production or
assembly of the type IV collagen
network in the basement membranes.
 kidneys are scarred and unable to filter
waste products resulting in hematuria
and renal disease.
Alport syndrome affecting eyes

19. Epidermolysis Bullosa
• Epidermolysis bullosa refers to a group of
inherited disorders that involve the
formation of blisters following trivial
trauma.
• CAUSE
 mutations in COL7A1, affecting the
structure of type VII collagen.
 Type VII collagen forms delicate fibrils
that anchor the basal lamina to
collagen fibrils in the dermis.
 These anchoring fibrils are reduced in
this form of the disease, causing friction
and blistering.
• EFFECT
 Blistering and painful sores like third
degree burns
Blister
formation

20. Osteogenesis Imperfecta
 Osteogenesis imperfecta or Brittle Bone Disease is a
genetic bone disorder due to decrease dcollagen
formation.
 CAUSE
 Mutations in the COL1A1 andCOL1A2 genes
coding for procollagen chains.
 Replacement of glycine by another bulkier
amino acid resulting in decreased collagen or
improper procollagen structure forming
abnormal fibers.
 Mutations also cause ‘procollagen suicide ‘
 All these cause brittleness.
 EFFECT
 Thin,t ransclucent, blue scleras.
 Affected infants may be born with multiple
fractures and not survive.
 weak muscles, brittle teeth, a curved spine and
hearing loss.

21. Chondrodysplasias
 Chondrodysplasias are a mixed
group of hereditary disorders
affecting cartilage.
 One example is Stickler
syndrome, manifested by
degeneration of joint cartilage
and of the vitreous body of the
eye.
 CAUSE
 Mutations in the COL2A1
gene, leading to abnormal
forms of type II collagen.
 EFFECT
 shortlimbed dwarfism
 skeletal deformities.

22. Osteolathyrism
 Osteolathyrism is a collagen cross-linking
deficiency caused by dietary over-
reliance on the seeds of Lathyrus sativus
(kesari dal) in some parts of India.
 CAUSE
 Osteolathyrogenic compounds like Beta-
aminopropionitrile(BAPN) and Beta-
oxalyl aminoalanine [BOAA] found in
Kesari dhal inhibit enzyme lysyl oxidase
required for the formation of cross links
in the triple helices
 EFFECT
 weakness and fragility of
skin, bones, and blood vessels
 Paralysis of the lower extremities
associated with neurolathyrism

23. Scurvy
 Scurvy is a disease due to deficiency of
vitamin C
 It is not a genetic disease.
 It is related to improper collagen
formation
 CAUSE
 Vitamin C [ascorbic acid ]is
required as a cofactor for
hydroxylase enzymes during the
hydroxylation of proline and lysine
in the synthesis of collagen.
 Deficiency causes impaired
collagen synthesis due to
deficiency of hydroxylases.
 EFFECT
 Bleeding of gums
 Poor wound healing
 Subcutaneous hemorrhages

24. Uses Of Collagen
 Industrial Uses
 Collagen is used as temporary thermoplastic glues in musical instruments like
violin and guitar .
 Recently used as a fertilizer
 Gelatin derived from the partial hydrolysis of collagen is used in food products like
desserts, jellies.
 It is also used in pharmaceutical, cosmetic, and photography industries.
 Medical uses
 Mild benefit to rheumatoid arthritis patients.
 Keeps the valvular leaflets of heart in shape.
 Helps in the deposition of calcium during aging.
 Used in cosmetic surgery, for burn patients for reconstruction of bone and a wide
variety of dental, orthopedic and surgical purposes.
 Main ingredient of cosmetic makeup.
 Human collagen is used for immunosuppression during transplantation.