1.13: Extracellular Matrix 1 Flashcards

1
Q

What is the defining feature of connective tissue?

A

Extracellular Matrix

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2
Q

What are the roles of connective tissues?

A

1) bind structures together
2) form a framework and support for organs and body as a whole
3) store fat
4) transport substances
5) protect against disease
6) help repair tissue damage

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3
Q

How are connective tissues characterized?

A

an abundance of intracellular matrix with relatively few cells

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4
Q

What is the extracellular matrix?

A

non-cellular components present within all tissues and organs

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5
Q

What is the ECM composed of?

A

water, proteins and polysaccharides

-some cells, non-living ground substance, collagen fibers, elastic fibers, reticular fibers

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6
Q

What’s the ECM role? (scaffolding and biochemically)

A

1) Physical scaffolding for cellular constituents
2) Initiates crucial biochemical and biochemical cues required for tissue morphogenesis, differentiation and homeostasis.

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7
Q

What are the two components of the extracellular matrix/extracellular macromolecules?

A

1) glycosaminoglycans

2) proteoglycans

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8
Q

What two things make up the ECM: Name two main classes of extracellular macromolecules and one more?

A

1) Proteoglycans: Glycosaminoglycans –> covalently linked to protein
2) Fibrous protein: fibronectin, laminin, elastin, collagen (FLEC)

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9
Q

Describe the composition of GAG?

A

-long unbranched chain polymers of repeated disaccharides containing an amino sugar.

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10
Q

What are the four major classes of GAG?

A

1) Hyaluronan
2) Chondroitin sulfate: (Dermatan–> 5th GAG class that’s associated with the chondroitin family)
3) Heparan sulfate
4) Keratan sulfate
(if you look at the structures, many of these molecules are sulfated)

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11
Q

Composition & Function of Hyaluronan/hyaluronic acid:

A

a disaccharide with glucuronic acid attached and is an extremely long and rigid GAG is composed of several thousand units of sugar.

  • NO PROTEIN CORE
  • Proteoglycans (GAGs+ core protein) link to hyoluronic acid via Link Protein = proteoglycan aggregates

Function: Cell migration in: embryogenesis, morphogenesis, wound healing.

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12
Q

Function of chondroitin sulfate?

A

Formation of bone, cartilage, cornea

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13
Q

Keratan sulfate?

A

Transparency of cornea

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14
Q

Heparan sulfate?

A

Component of skin fibroblasts and aortic wall, commonly found on cell surfaces

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15
Q

What are proteoglycans?

A

another class of macromolecules of the cell surface or ECM where one or more GAG chains are joined covalently to a membrane or secreted protein.

-the carbhydrate portion forms the greater fraction by mass

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16
Q

What are proteoglycan aggregates?

A

when proteoglycans are attached to hyaluronic acid via a Linker protein. ( PROTEOGLYCAN (GAGS) + LINKER PROTEIN + HYALURONIC ACID)

17
Q

How are proteoglycans classified?

A

classified according to their core proteins, localization and GAG composition.

18
Q

What are the three proteoglycan families?

A

1) Small leucine-rich proteoglycans (SLRPS)
2) Modular proteoglycans (family of proteins where they all share similar domains)
3) Cell-surface proteoglycans (These proteoglycans are embedded into membrane)

19
Q

What are the properties of proteoglycans? (3)

A

1) Highly hydrophilic and accordingly adopt extended conformations
2) Conformations essential for hydrogel formation
3) enables matrices that are formed by these molecules to withstand high compressive forces.

20
Q

Pros of negatively charged proteoglycans?

A

They attract ions and water, thus forming a gel.

21
Q

Role of the poylsaccharide gel in proteoglycans?

A
  • Resists compressive forces on the matrix

- Permit rapid diffusion of nutrients, metabolites and hormones between the blood and the tissue cells.

22
Q

Role of collagen fibers in ECM?
Role of Elastin fibers in ECM?
Role of protein fibers in ECM?

A
  • Help strengthen and organize the ECM
  • Rubberlike elastin fibers give it resilience.
  • Matrix proteins help cells attach in the appropriate locations
23
Q

Can proteoglycans form proteoglycan aggregates?

A

Yes, some can.

24
Q

What is the composition of Hyaluronate as a biological shock absorber?

A
  • composed of repeating units of D-glucuronate and N-acetyl-D-glucosamine linked through 1-3Beta glycosidic bonds.
  • This repeating disaccharides are linked by 1-4Beta glycosidic bonds
  • Beta configuration gives polymer a stretched conformation, made more linear because of electrostatic repulsion of negative charge.
  • Because of the negative charge, the strand is now heavily solvated with water; therefore, giving remarkable viscosity and tensil properties.
25
Q

Role of Syndecan-1?

What does Syndecan bind?

A

Proteoglycan can be anchored in the membrane (Syndecan-1): plays important role in inflammation/wound healing)
Syndecan-1 binds CHEMOKINES.
- When epithelia are damaged, these complexes are released and diffuse away forming a chemotactic gradient that attracts neutrophils to the site.
-Syndecan-1 also plays important role in cell binding and cell signaling.

26
Q

Synthesis of proteoglycans in the cell? (Anabolism)

A
  • The protein backbone is formed at the rough endoplasmic reticulum
  • Protein chain is then transferred to golgi and sugars are added forming GAGs
  • GAGs leave golgi and become part of the cell membrane.
27
Q

Breaking down of proteoglycans in the cell? (Catabolism)

- What are the requirements for these breakdowns?

A
  • Proteogylcans are taken into the cell by endocytosis and degraded by lysosomes
  • Amino acids and sugars in proteoglycans are recycled when ever possible
  • Requires 3 exoglycosidases, 4 sulfatases, and 1 acetyl transferase with stepwise removal of monosaccharides.
28
Q

Where does normal catabolism occur? (proteoglycans)

A

seen in remodeling of cartilage and bone

29
Q

where does abnormal catabolism occurs? (proteoglycans)

A

seen in arthritis and tumor invasions

30
Q

Where do most breakdowns occur?

-What do inhibitors here do?

A

via lysosomal pathways.

- inhibitors reduce break down of linear proteins by extracellular proteases.

31
Q

What are GAG defects?

A Lysosomal storage disease.

A
  • normally due to an enzyme deficiency and so proteoglycans get accumulated.
  • Chondroitin sulfate and hyaluronate do no accumulate because they can be catalyzed via a different pathway… so it’s usually with heparan or dermatan sulfate.
  • due to autosomal recessive or X linked
  • there are severe and mild forms of the disease
  • Not apparent at birth
    ex: Hunter disease
    -