collagen report structure, function and abnormalities)(1)
TRANSCRIPT
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(STRUCTURE, FUNCTION ANDABNORMALITIES)
COLLAGEN
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COLLAGEN
most abundant fibrous protein in the animalkingdom.
major component of most connective tissue.
25 to 30 percent of the total protein in the
human body.
comprises three polypeptide chains (a-chains)
which form a unique triple-helical structure.
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Types I, II and III are the most abundant and
form fibrils of similar structure.
25 distinct types of collagen made up over 30distinct polypeptide chains (different collagen
genes ).
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Functions:
provides strength, support, integrity, and
structure.
needed to repair tissue defect and to restore
structure and function.
Major determinant of ones appearance
(Amount and Quality)
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4 CommontypesofCollagen:
Type I Collagen
-forms a triple helix composed of three chains or strands
-1050 amino acids and approximately 300 nanometers long
-extremely strong (its strength per unit mass is greater than steel )
-forms the primary component oftendons, connective tissuestructures that link muscles and bones. Collagen type I also helps
reinforce your bones.
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Type II Collagen
-forms the primary component ofcartilaginous tissue found in
nose, ears and many joints in your body.
- smaller than collagen type I fibrils and assume randomorientations in a gelatinous matrix of protein-carbohydratecomplexes, where they cross-link with collagen type IX.
-associated with proteoglycans or "ground substance" andtherefore functions as a shock absorber in our joints and vertebrae.
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Type III Collagen-found in our skin as well as in blood vessels and internal organs.
-often withType I collagen, arranged in loose network.
-adult, the skin contains about 80-percentType I and 20-percentType III collagen. In newborns, theType III content is greater thanthat found in the adult.
-During the initial period of wound healing, there is an increasedexpression ofType III collagen.
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Type IV Collagen-found in basement membranes and basal lamina structures and
functions as a filtration system.
-has a complex interactions in noncollagenous components of thebasement membrane, a meshwork is formed that filters cells as wellas molecules and light
ex.
1. lens capsule of the eye, the basement membrane plays a rolein light filtration
2. In the kidney, the glomerulus basement membrane isresponsible for filtration of the blood to remove waste products.
3. In the walls of blood vessels, basement membrane controlsthe movement of oxygen and nutrients out of the circulation and
into the tissues.
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Type V Collagen-found in essentially all tissues and is associated withTypes I and III.
-often found around the perimeter of many cells and functions as a
cytoskeleton (particularly abundance in the intestine).
-cells surfaces, hair and placenta.
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Other TypeofCollagen:
Type Notes Gene Code Disorder
I present in scar tissue, the end product when tissue healsby rskin, artery walls, the endomysium of myofibrils,fibrocartilage, and the organic part of bones andteethepair. It is found in tendons,
COL1A1, COL1A2 osteogenesis imperfecta, Ehlers-Danlos Syndrome, Infantile
cortical hyperostosis aka Caffey'sdisease
IIHyaline cartilage, makes up 50% ofall cartilage protein.
Vitreous humour oftheeye.
COL2A1 Collagenopathy, types II and XI
III produced quickly by young fibroblasts before thetougher type I collagen is synthesized. Reticular fiber.Also found in artery walls, skin, intestines and the uterus
COL3A1Ehlers-Danlos Syndrome,
Dupuytren's contracture
IV basal lamina; eye lens. Also serves as part of thefiltration system in capillaries and the glomeruli ofnephron in the kidney.
COL4A1, COL4A2, COL4A3,
COL4A4, COL4A5, COL4A6
Alport syndrome, Goodpasture'ssyndrome
V most interstitial tissue, assoc. with type I, associatedwith placentaCOL5A1, COL5A2, COL5A3 Ehlers-Danlos syndrome
VI most interstitial tissue, assoc. with type I COL6A2, COL6A3 Ulrich myopathy and Bethlemmyopathy
VII formsanchoring fibrils indermal epidermal junctions COL7A1 epidermolysis bullosadystrophica
VIII someendothelial cells COL8A1, COL8A2 Posteriorpolymorphous cornealdystrophy 2
IX FACIT collagen, cartilage, assoc. with type II and XIfibrilsCOL9A1, COL9A2, COL9A3 - EDM2 and EDM3
X hypertrophic and mineralizing cartilage COL10A1 Schmid metaphyseal dysplasia
XI cartilage COL11A1, COL11A2 Collagenopathy, types II and XI
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Type Notes Gene Code Disorder
XII FACIT collagen, interacts withtype I containing fibrils, decorinand glycosaminoglycans
COL12A1
XIII integrin a1b1, fibronectin andcomponents of basementmembranes like nidogen andperlecan.
COL13A1
XVII transmembranecollagen, alsoknown as BP180, a 180 kDaprotein
COL17A1 Bullouspemphigoid and certain
forms of junctional epidermolysis
bullosa
XXIX epidermal collagen COL29A1 Atopic dermatitis
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GeneralstageofCollagen
Synthesis:
mRNA synthesis
protein synthesis
post-translational modifications
degradation
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StructureofCollagen:
With unusual amino acid composition
Glycine, Proline and Hydroxyproline are arranged inrepetitious tripeptide seqeunce.
Gly-X-Y
X- any Amino Acid or frequenly Proline
Y- Hydroxyproline or Hydroxylysine
Glycine (Gly) is found at almost every third residue
Proline (Pro) makes up about 17% of collagen
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Insidethecell (Intracellular)
1. mRNA Processing
-mRNA for eachcollagen type is
transcribed fromthe gene (DNA
blueprint)
2. Translation
-2 peptide Chain is
produced:
Alpha-1 and Alpha-2
chain(preprocollagen)
* registration peptides
* signal peptide
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- found in membranous-bound
ribosomes(rER)
- Polypeptide chains are released
into the lumen of the RER
-Signal peptides are cleaved insidethe RER (central proteinsysthesis)and the chains are now
known as pro-alpha chains.
3. Hydroxylation
Proline & Lysine (HYROXYLASES)formed: Hydroxyproline
Hydroxylysine
-which need cofactor to secure
the integrity of helical structure.
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4. Glycosylation
-Galactose and Glucose
-Catalyzed by
Galactosyl & Glucosyl traferases
* Triple helical structure is formed
inside the endoplasmic reticulumfrom each two alpha-1 chains and
one alpha-2 chain.
Procollagen (larger precursor
molecules) is shipped to the golgiapparatus, where it is packaged and
secreted by exocytosis.
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OutsidetheCell(Extracellar)
Registration peptides arecleaved and tropocollagen is
formed by procollagenprotienases.
Cross-link formation
-Multiple tropocollagen
molecules form collagen fibrils,via covalent cross-linking (aldol
reaction) by lysyl oxidase which
links hydroxylysine and lysineresidues. Multiple collagen fibrilsform into collagen fibers
Collagen may be attached to cellmembranes via several types of
protein, including fibronectin
and integrin.
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Primary structure of a protein is thesequence of amino acids.
Secondary protein structure occurs
when the sequence of amino acidsare linked by hydrogen bonds. This
level of structure takes the form of
either a pleated sheet or a helix. Tertiary structure describes the
folding and other contortions of apolypeptide chain that result from
the molecular interactions amongthe R groups of the different amino
acids. The arrangement of two or more
polypeptide chains in a proteinmake up its quaternary structure
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Vit.C inCollagenformationand
Functions:
Proline and Lysine residues
-Hydroxyproline and Hydroxylysine by
Prolyl hydroxylase & Lysly hydroxylase
Vit.C - essential for proper structural allingment.
-development, replacement and maintenance connective tissue,blood vessel and cartilage.
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Collagenin woundrepair
Wound repair - a complex and dynamic process ofrestoring cellular structures and tissue layers
Hemostasis - platelets
Inflammation neutrophils, macrophage, metalloproteinase
Granulation - tissue granulation and vascularisation; fibroblasts laydown new collagen and other proteins; ECF is now functional
Remodeling fibroblasts will remodel and link the collagen fibers
Collagen structural support; cleavage products from collagen degradationstimulates fibroblast and vascular endothelial cells proliferation
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Collagenin woundrepair
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Hemostasis
Platelets aggregate around exposed collagen
release of factors strengthens aggregate =
platelet plug
Release of cytokines inflammatory cells
(neutrophils, macrophage, eosinophils)
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Inflammatory
Activated macrophage increase in inflammatory
cytokines migration of
fibroblasts, epithelial cells,and vascular endothelialcells into the wound =cellularity of the wound
increases
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Proliferation
Cleavage productsresulting from collagen
degradation stimulate
fibroblast proliferation Metalloproteinasedegrades the nonviablecollagen
Stimulation of vascularendothelial cellproliferation =
Angiogenesis
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Tissue inhibitors = decrease in
metalloproteinase = increase collagen
deposition of fibroblast New collagen + blood supply = functional
ECM granulation
Keratinocytes migrate to newly formedgranulation tissue = reepithelialization
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RemodelingPhase
Angiogenesis ceases
Fibroblasts will
remodel and cross link the collagen fibers= stronger scar
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CollagenandAging
The increasingly brittle and rigid character of agingconnective tissue results from accumulated covalentcross-links.
Heat disruption of forces shortening
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CollagenandAging
Increase in collagenase underexpression ofinhibitors conversionof fibroblast to
fibroclast degradation of ECF
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DISEASES AND GENETIC
DISORDERS
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Osteogenesis Imperfecta
Hereditary disease of thebones and connectivetissue due to mutation ofgene encoding inType I
collagen
Hypermobility of joints
Fragile bones
Poor teeth
Growth retardation
Blue sclera
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Ehlers-Danlos Syndrome
a group of more than 10different inherited
disorders; all involve a
genetic defect in collagenand connective tissuesynthesis and structure.
can affect the skin, joints,and blood vessels
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Ehlers-Danlos Syndrome
Hyperextensibility of theskin
Abnormal tissue fragility
Increased joint mobility
Ehlers Danlos syndrometype IV is associated with
rupture of arteries or thebowel, with possible life-threateningconsequences
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Alport Syndrome
heterogeneous geneticdisorders affecting thestructure of type IVcollagen, a majorcomponent ofbasement membranes(renal glomeruli).
Hearing loss
Hematuria
May develop end stagerenal disease
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DystrophicEpidermolysis Bullosa
a group of inheritedbullous disorderscharacterized byblistering lesions onthe skin and mucusproduction areas
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Basementmembrane zone
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DystrophicEpidermolysis Bullosa
caused by defects ofanchoring fibrils (Type VII
collagen)
Blisters most commonlyappear at sites of friction
and minor trauma such asthe feet and hands
may also occur on internalorgans, such as theesophagus, stomach andrespiratory tract, withoutany apparent friction
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Thank You!!