Extracellular Matrix & Connective Tissue Chemistry

8/10/2019 Extracellular Matrix & Connective Tissue Chemistry

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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

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37


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Banded appearance of collagen

fibrils

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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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Extracellular Matrix & Connective Tissue Chemistry

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