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EXTRA CELLULAR
MATRIX
(ECM)or Connective Tissue
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Introduction
Most mammalian cells are located in tissues
where they are surrounded by a complex
extracellular matrix (ECM) often referred to
as connective tissue.
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Introduction contd
It plays important roles in:
-development
- inflammatory states &
- in the spread of cancer
Its involvement is documented in several
diseases, eg, osteoarthritis, osteogenesisimperfecta and Ehlers-Danlos syndrome
Mucopolysaccharidoses is also caused by the
genetic disorders of ECM
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The connective tissue underlying an
epithelial cell sheet
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Major Biomolecules of ECM
The ECM contains threemajor classes of
biomolecules:
(1) the structural proteins, collagen,
elastin, and fibrillin;
(2) certain specialized proteins such as
fibrillin, fibronectin, and laminin; and
(3) proteoglycans,
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Collagens Major component of ECM, constituting 25%of
all proteins in mammals.
At least 19 different types of collagens, have
been found in humans tissues.
They are distributed in various tissues such asskin, bone, tendon, blood vessels, cornea,cartilage, intervertebral disks and vitreousbody as fibril-forming
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Collagens-Structure
Most collagens are triple helical (three
chains).
The repeating sequence of the helix is Gly-X-Ywhere X is often proline Y is often hydroxy proline or
hydroxy lysine (about 100 of each).
Proline and hydroxy proline confer the rigidity(strength) on the collagen molecule.
Ascorbic acid and ketoglutarate are cofactors forthe enzymes
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Hydroxylation of Proline
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Triple-stranded helix of collagen
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The structure of a typical collagen molecule
(another view)
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Electron micrograph of collagen
fibrils from skin
Page2
37
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Banded appearance of collagen
fibrils
Page237
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Electron microscope of a polygonal
network of collagen type IV
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Collagen diseases
Defects in any one of the many steps in
collagen synthesis can occur
Ehlers-Danlos syndrome(EDS) is agenetic disorder in collagen molecule
EDS can result from the deficiency of theenzymes (hydroxylase) or mutations in the
amino acid sequences in collagen synthesis
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Stretchy skin of EDS
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The legs of 48 year old man with
scurvy (ascorbic acid deficiency)
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Elastin
Elastin is a connective tissue protein withrubber-like properties.
It is present in the lungs, the walls of largearteries, bladder and elastic ligaments.
They can be stretched to several times theirnormal length, but recoil to their original
shape when the stretching force is relaxed.
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Fibrillin, Fibronectin & Laminin
Fibrillin is a large glycoprotein which is astructural component of microfibrils
Marfan syndromeis due to mutation in the
gene for fibrillin, which affects lens, skeletalsystem and cardiovascular system
Fibronectin is a important glycoprotein
involved in cell adhesion and cell migration Laminin is major protein component of renal
glomerular and other basal laminas
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Proteoglycans & Glycosaminoglycans (GAGs)
Glycosaminoglycans are usually linked toproteins to form proteoglycans
They are called GAGs, because one or twosugars in the repeating unit are amino sugars(N-acetylglucosamine, N-acetylgalactosamine)
which are sulfated.
The other sugar is uronic acid
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Proteoglycans aggregate from fetal
bovine cartilage
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Glycosaminoglycans (GAGs)
There are at least 7 GAGs, 1. Hyaluronic acid (HA)
2. Chondroitin sulfate (CS)
3. Keratin sulfate I (KS I) 4. Keratin sulfate II (KS II)
4. Heparin (H)
5. Heparin sulfate (HS)
6. Dermatan sulfate (DS)
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STRUCTURES OF REPEATING SUGARS
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