COLLAGEN

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WHAT’S AHEAD
Properties
Structure
Sources
Synthesis
Degradation
Uses and Applications
most abundant protein in the human body
 Collagen consists of three polypeptide
chains, each twisted into a left-handed helix
 Collagen is rich in hydroxylysine and
hydroxyproline moieties, which enable it to
form strong cross-links
 Major Types of Collagen
a) Type I
-found throughout the body except in
cartilaginous tissues
-synthesized in response to injury and in the
fibrous nodules in fibrous diseases
-over 90% of the collagen in the body is Type
I
 Major Types of Collagen
a) Type I
-synthesized from the genes COL1A1 &
COL1A2
-mutations of genes: Osteogenesis
Imperfecta
 Major Types of Collagen
b) Type II
-main component of cartilage; found in
developing cornea & vitreous humor
-formed from 2 or more collagens or co-
polymers
-synthesized from COL2A1
 Major Types of Collagen
c) Type III
-found in extensible connective tissues
-usu. occurs in the same fibril with Type I
collagen
-synthesized from COL3A1
 Major Types of Collagen
d) Type IV
-forms the bases of cell basement membrane
-genes: COL4A1-COL4A6
 Major Types of Collagen
e) Type V
-minor components of tissue; occurs as
fibrils with Type I & Type II collagen,
respectively
-forms cell surfaces, hair, & placenta
-genes: COL5A1-COL5A3
 Major Types of Collagen
f) Type VI
-present in most connective tissues
-genes: COL6A1-COL6A3
PROPERTIES
PROPERTIES

(etymology): Greek word meaning, “Glue”; it

is so named since it holds the cells together
in the tissues
PROPERTIES

remains soft and flexible under low stress

and becomes stiffer when stress is increased
STRUCTURE
 a molecule that
is composed of three polypeptide chains,
each of which contains one or more regions
characterized by the repeating amino acid
motif (Gly-X-Y), where X and Y can be
any amino acid
STRUCTURE
SOURCES
SOURCES

Originated from vertebrate animals such as

humans, cows, pigs, and sheep.
SYNTHESIS
SYNTHESIS

Intracellula Extracellula
Secretion
r r

3 Major Stages involving the Synthesis of Collagen

 SYNTHESIS

Intracellular Steps: synthesized intracellularly in the fibroblasts (or

in osteoblasts of bone and chondroblasts of cartilages) as a large
precursor, called pre-pro-collagen; synthesized on ribosomes

a) Transcription & Translation

-genes for pro α-chains are transcribed on mRNA; moves into the
cytoplasm and interacts with ribosomes for translation
-mRNA is translated on to rough endoplasmic reticulum (RER) into
pre-pro-collagen
 SYNTHESIS

b) Post-translational Modification
Formation of pro α-chain
-the leader sequence of the pre-pro-collagen acts a signal that the
polypeptide being synthesized (i.e. the pre-pro-collagen) is
destined to leave the cell; signal sequence directs the passage of
the polypeptide chain into the cisternae
signal of the RER
peptidase
signal sequence pro-α-chain
 SYNTHESIS

b) Post-translational Modification
Hydroxylation
-Pro & Lys residues are hydroxylated by enzymes prolyl hydroxylase
& lysyl hydroxylase, respectively,; this step requires Vit. C as co-
factor
SYNTHESIS

Hydroxylation of Pro & Lys

 SYNTHESIS

b) Post-translational Modification
Glycosylation
-some hydroxy Lys are modified by glycosylation with galactose or
galactosyl-glucose through an O-glycosidic linkage (glycosylation
site that is unique to collagen)
SYNTHESIS
 SYNTHESIS

Assembly
-cardinal principle in the biosynthesis of collagen
-hydroxylated and glycosylated pro α-chains will twist around each
other to form a triple helix known as procollagen
-procollagen molecule contains extension peptides at both its N-
terminus & C-terminus (neither of which is present in mature
collagen); both contain Cys residues
-formation of disulfide bonds assist in the assembly of the three
collagen molecules to form the triple helix, winding from the C-
terminus
 SYNTHESIS

Secretion: procollagen molecules are translocated to the Golgi

apparatus where they are packaged in secretory vesicles
: the vesicles fuse with the cell membrane, causing the
release of procollagen molecules in to the extracellular
space
 SYNTHESIS

Extracellular Steps: involves outside of the cell to form mature

collagen molecules

a) Cleavage of N-terminus & C-terminus propeptides

-extracellular enzymes, procollagen aminoproteinase & procollagen
carboxyproteinase, remove the extension peptides at the N-
terminus & C-terminus, respectively, releasing triple helical collagen
molecules => tropocollagen
 SYNTHESIS

b) Formation of collagen fibrils

-the triple helical collagen molecules, containing approx. 1000
amino acids per chain, spontaneously assemble into collagen fibers
 SYNTHESIS

c) Cross-link formation
-collagen fibers are further stabilized by formation of covalent
cross-links (both within & between the triple helical units)
-form through the action of lysyl oxidase, yielding reactive
aldehydes
-such aldehydes can form aldol condensation products with other
Lys- or hydroxyl Lys-derived aldehydes or form Schiff bases with the
Ʃ-amino groups of unoxidized Lys or hydroxyl Lys => these
reactions, after further chemical arrangements, result in the stable
covalent cross-links important for the tensile strength of the fibers
 S

SYNTHESIS
M
DEGRADATION
DEGRADATION

-Collagen is broken down by proteolytic action of

collagenases
-group of collagenases belong to a family of enzymes
called matrix metalloproteinases (MMPs)
-some cells in our body that synthesize & release
collagenase including fibroblasts, macrophages,
neutrophils, osteoclasts, & tumor cells
 USES &
APPLICATIONS
 USES &
APPLICATIONS

Medical Use

a) Wound dressing- collagen can help heal wounds by attracting new skin cells
to the wound site. It promotes healing and provides a platform for new tissue
growth.
b) Guided tissue regeneration- collagen-based membranes have been used in
periodontal and implant therapy to promote the growth of specific types of
cell.
c) Vascular prosthetics- collagen tissue grafts from donors have been used in
peripheral nerve regeneration, in vascular prostheses, and in arterial
reconstruction.
 USES &
APPLICATIONS

Cosmetic Use

a) Skin fillers- collagen injections can improve the contours of the skin and fill
out depressions. Fillers that contain collagen can be used cosmetically to
remove lines and wrinkles from the face.
b) Skin revitalization- many products containing collagen, including creams and
powders, claim to revitalize the skin by increasing collagen levels within the
body. This is unlikely, however, as collagen molecules are too large to be
absorbed through the skin.