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B I O C H E M I S T RY

C O L L A G E N P R E S E N TAT I O N
GROUP MEMBERS:
NATASHA ALLADIN
DAVENDRA CARTER
JONELLE EUROPE
LATIFA HENRY
THERESA
JAIKISHUN
TOSNAUSHA
LOGAN
AZALIA LUKE
SHARICE RAZACK
TAMARA WILLIAMS

OBJECTIVES
1. Outline the structure and biochemical function of collagen
Types
Structure
Function and Biosynthesis

2. Discuss disorders in relation to structure and function


Degradation and remodeling
Biomedical applications
Collagen diseases and treatment

INTRODUCTION

Collagen is the most abundant fibrous protein in the

body
It functions to provide mechanical support and structure

within the body


It is found in various parts of the body such as the skin,

bones, teeth and ligaments and tendons


There are many different type of collagen, Type 1 being the

most abundant

TYPES OF COLLAGEN
Type

Tissue distribution
Fibril forming

Skin, bone, tendon, blood vessel ,cornea

ii

Cartilage ,inter-vertebral disk, vitreous


body

iii

Blood vessel, fetal skin


Network forming

iv

Basement membrane

vii

Beneath stratified squamous epithelia


Fibril associated

ix
xii

Cartilage
Tendon ligaments

1. Fibril-forming collagens:
Types I, II, and III are the fibrillar collagens; Have

rope like structures.


In the electron microscope, these linear polymers

of fibrils have characteristic banding patterns,


reflecting the regular staggered packing of the
individual collagen molecules in the fibril .
Location:
TYPE 1
Tendon
Cornea

TYPE II
Cartilaginous
structures

TYPE III
Distensible tissues
e.g. Blood vessels

2. Network-forming collagens:
Types IV and VII form a three-dimensional mesh,

rather than distinct fibrils.


For example, type IV molecules assemble into a

sheet or meshwork that constitutes a major part


of basement membranes.
3. Fibril-associated collagens:
Types IX and XII bind to the surface of collagen

fibrils, linking these fibrils to one another and to


other components in the extracellular matrix.

STRUCTURE OF COLLAGEN
Amino acid sequence
Each polypeptide chain has precisely 1050 amino acid

residues.
The primary structure of collagen is rich in glycine and

proline.
Proline facilitates the helical conformation of each alpha

chain, since its ring structure links polypeptide chain. Glycine


on the other hand is found in every third position of the
polypeptide chain.

TRIPLE HELIX STRUCTURE

The -chains are then twisted around one another in a rope-like manner to produce the
overall tightly packed triple-helical form of the molecule.

The main bonds associated are inter hydrogen bonds and covalent cross links.

About 1/3 of the AA composition of collagen is gly. It is the smallest AA which allows
three strands to sit closer to each other to form a tight coil.

Collagen has a repetitive sequence of gly-x-y . For each gly-x-y triplet a hydrogen bond
if formed between the amide H atom of gly and the carbonyl O atom of residue X in at
adjacent chain.

Proline allows the formation of a tightly wound helical conformation, because its ring
structure causes kinks in the polypeptide chain.

HYDROXYPROLINE AND
HY DRO XY LYCI NE
Hydroxyproline is essential in stabilizing the

helical structure because it maximizes interchain-hydrogen bond formation.


Collagen fibrils are strengthened and stabilized

mainly by covalent cross links occurring by the


C and N terminals involving Lys and Hyl.
Some Hyl residue are covalently bonded to

carbohydrate residues, making collagen a glycol


protein.

BIOSYNTHESIS

Preprocollagen

Hydroxylation

Glycosylation

Procollagen

Triple Helix

Cleavage

Tropocollagen

Collagen

Cross Links

Functions of collagen
Strength
Bone

Blood
Vessels

Flexibility / Elasticity

Support/ Structure

Bone is made up of a mixture of collagen and a mineral called hydroxyapatite. The two work
together to form the structure, flexibility and strength of your bones.

Collagen makes up the walls of the veins, arteries and capillaries of the body. This gives the
vessels strength, structure and flexibility, all of which are needed to effectively transport blood
throughout your entire body

Collagen fibers provide your muscles with the strength and structure needed to move and

Muscles

function throughout the day. Collagen fibers makes up your skeletal muscle fibers, smooth
muscles) and cardiac muscles.

Skin

Allows skin the flexibility it


needs to stretch and return
to its original state as your
body moves

Collagen makes up
approximately 80 percent of
the dry weight of your skin. It
provides structure to the skin

Major component of extracellular fluid


Assist in the hydration of tissues.

D E G R A D ATI O N
Causes of collagen to break down
Collagenase -enzyme
Too much sugar in the diet -increase glycation
Sunlight - damages the fibers and induces irregular elastin

which further breaks down collagen


Autoimmune disease - attack collagen tissue and may

cause irregular collagen


Smoking

S AVE TH E C O L L A G EN

Laser - stimulates skin


Fascial Light Therapy - reduces sun damage
Sunscreen - reduces sun damage
Vitamin C Treatment - helps in production of 2

Amino Acids that help make collagen

BIO MEDICAL APP LICATION


Collagen is seen as the most and safe biomaterial due to its

biocompatibility (Biodegradability, Weak antigenicity).


It is useful because of the extra strength and stability through

its: Self-aggregation and Cross linking capabilities.


Its uses can be classified into two broad categories
1. Collagen based drug delivery system

Film/sheet/disc e.g. treatment of infected corneal and


cancer tissues; Collagen film as a calcifiable matrix system
e.g. in cardiology; Collagen sponges e.g. wounds; Collagen
shields e.g. opthalmic applications; Gel, hydrogen liposomes
collagen; Pellet/tablet e.g. drug delivery

2.Collagen based systems for tissue engineering


Collagen as skin replacement e.g.

reconstructive surgeries
Collagen as bone substitutes e.g. cosmetic

surgeries
Collagen as bioengineered tissues

COLLAGEN DISEASES/
DISORDERS
1. Collagen biosynthesis defects
. The best-known is Scurvy, results from a dietary deficiency of

vitamin C required by prolyl and lysyl hydroxylases.


. These Fe2-containing enzymes require ascorbic acid for activity.
. Collagen does not form correctly due to the inability to

hydroxylate Pro and Lys.


. The resulting deficit in the number of hydroxyproline and

hydroxylysine residues undermines the conformational stability


of collagen fibers, leading to bleeding gums, swelling joints, poor
wound healing, and ultimately to death.

C O L L A G E N VAS C U L A R D I S E A S E S
Rheumatoid arthritis (RA) - the immune system attacks the thin membrane

(called the synovium) lining the joints, causing pain, stiffness, warmth and
swelling of the joints, and inflammation throughout the body.
Polymyositis and dermatomyositis - two related diseases in which there is

inflammation of the muscles (polymyositis) and skin (dermatomyositis).


Scleroderma - group of disorders that causes thick, tight skin, buildup of scar

tissue, and organ damage.


Systemic lupus erythematosus - (SLE or simply lupus) is a disease

characterized by inflammation of the joints, skin, and internal organs.


Marfan Syndrome affects collagen of the heart, eyes, bones, lungs and spinal

cord by carrying the gene fibrillin -1.


Alports Syndrome is a defect in collagen type 4 and an inherited form of kidney

inflammation, damaging tiny blood vessels.

GENETIC DISORDERS OF
COLLAGEN BIOSYNTHESIS

Ehlers-Danlos Syndrome (EDS)


Heterogeneous group of generalized connective tissue disorders

that result from inheritable defects in metabolism of fibrillar


collagen molecules.
The most clinically important mutations are in the gene for type III

collagen.
Potentially lethal vascular problems occur.
Patients also show defects in collagen type I fibril, which result in

stretchy skin and loose joints

OSTEOGENESIS IMPERFECTA (OI)

Also known as brittle bone syndrome, is heterogeneous group of

inherited disorders distinguished by bones that easily bend and


fracture.
Common features include: retarded wound healing and a rotated

and twisted spine leading to humped-back appearance.


There two types: Type I OI (Osteogenesis imperfecta tarda), Type II

OI (Osteogenesis imperfecta congenita)


Most patients with severe disease have mutations in the gene for

type I collagen.
The structurally abnormal chains prevent folding of the protein into

triple-helical conformation.

REFERENCES
Jones D, Hosalkar H, Jones S. The orthopaedic management of
osteogenesis imperfecta. Clin Orthop. 2002. 16:374-88.
Zeitlin L, Fassier F, Glorieux FH. Modern approach to children with
osteogenesis imperfecta. J Pediatr Orthop B. 2003 Mar. 12(2):77-87.
[Medline].
Forin V. [Paediatric osteogenesis imperfecta: medical and physical
treatment]. Arch Pediatr. 2008 Jun. 15(5):792-3. [Medline].
Esposito P, Plotkin H. Surgical treatment of osteogenesis imperfecta:
current concepts. Curr Opin Pediatr. 2008 Feb. 20(1):52-7. [Medline ].
http://onlinelibrary.wiley.com/doi/10.1002/bip.360210507/abstract
http://www.biochemj.org/bj/316/0001/3160001.pdf

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