Chapter 6: Proteins Of The Extracellular Matrix Flashcards
(72 cards)
1
Q
Extracellular matrix
A
Connective tissue (CT) surrounding cells and organs.
2
Q
Three types of protein found in ECM
A
- Structural proteins
- Specialized proteins
- Proteoglycans
3
Q
Structural proteins
A
- Collagen
- Elastin
4
Q
Specialized proteins
A
- Fibronectin
- Fibrillin
- Laminin
5
Q
Proteoglycans
A
Gags attached to a core protein.
6
Q
Collagen synthesis
A
Fibroblasts
7
Q
Collagen sites
A
- Skin
- Bones
- Cartilage
- Tendons
- Blood capillaries
- Cornea
- Ligaments
8
Q
Collagen percentage
A
25% of total body proteins.
9
Q
Collagen unit
A
Tropcollagen is the structural unit and is made up of 3 a chains.
10
Q
Types of collagen
A
More the 20 types but the most common are:
1. Type 1 (90%): formed of (a1-2, a2).
2. Type 2: formed of (a1-3).
11
Q
a-chain consists of how many amino acids?
A
1050
12
Q
a-chain unit
A
Consists of repeated units of Glycine-X-Y.
13
Q
a-chain X
A
Proline
14
Q
a-chain Y
A
Hydroxyproline
15
Q
a-chain X occupied by
A
Sometimes Lysine.
16
Q
a-chain Y occupied by
A
Sometimes by Hydroxylysine.
17
Q
How much alanine is found in a-chain?
A
10%
18
Q
Tropocollagen
A
Structural unit of collagen.
19
Q
Tropocollagen structure
A
- Triple helical molecule contains 3 a chains, each chain is twisted to form a left-handed helix.
- 3 amino acids in each turn.
- The 3 chains are then twisted to form a right-handed superhelix.
- Galactose and/or glucose are added (collagen is a glycoprotein).
- Tropocollagen molecules assemble in a staggering manner into fibrils then packed to form collagen fibers.
20
Q
What prevents the Tropocollagen molecules from forming a right-handed helix?
A
Presence of proline.
21
Q
Why does collagen have a very firm structure?
A
HHEFFS
1. High content of glycine: the polypeptide chains are very close to each other.
2. High content of Hydroxyproline: formation of hydrogen bonds.
3. Each turn contains only 3 amino acid residues: tight helix.
4. Formation of right-handed superhelix.
5. Formation of covalent cross links between adjacent polypeptide chains.
6. Specific arrangement into fibrils and fibers.
22
Q
Synthesis of collagen by?
A
Fibroblasts.
23
Q
Steps of collagen synthesis
A
- Intercellular reactions.
- Extracellular reactions.
24
Q
Intracellular reactions
A
- Synthesis of preprocollagen a chains.
- Conversion of preprocollagen a chain to procollagen a chain.
- Formation of procollagen.
- Exocytosis.
25
Synthesis of preprocollagen a chains
- By ribosomes of rough endoplasmic reticulum.
- Preprocollagen a chains contain:
1. 2 extension peptides:
* N extension peptide.
* C extension peptide.
2. Signal peptide: directs the polypeptide chain into the endoplasmic reticulum.
26
Conversion of preprocollagen a chain to precollagen a chains
1. Removal of signal peptide by signal peptidase.
2. Hydroxylation of proline and lysine residues by prolyl and lysyl hydroxylase. They require vitamin C.
3. Glycosylation of hydroxylysyl residues:
- Addition of glucose by glucosyl transferase.
- Addition of galactose by galactosyl transferase.
27
What is caused by vitamin C deficiency?
Scurvy, characterized by impaired collagen synthesis.
28
Formation of procollagen
1. Oxidation of cysteine residues and formation of disulfide bonds at the C terminal extension peptide and formation of triple helix.
2. Completion of glycosylation in Golgi apparatus.
29
Exocytosis
Procollagen is exocytosis outside the cell.
30
Extracellular reactions
1. Formation of Tropocollagen.
2. Formation of inter chain cross links.
3. Formation of collagen fibrils and fibers.
4. Maturation of collagen.
31
Formation of Tropocollagen
1. Removal of N extension peptide by aminoproteinase.
2. Removal of C extension peptide by carboxyproteinase.
32
Formation of inter chain cross links
By lysyl oxidase (contains Cu2+).
33
Formation of collagen fibrils and fibers
1. Tropocollagen molecules assemble in a staggering array into fibrils then packed to collagen fibers.
34
Maturation of collagen
By formation of Intra and intermolecular cross linkages between lysine and allysine.
35
Why does collagen become more flexible by age?
Due to the increase of covalent cross links.
36
Action of lysyl oxidase and covalent cross link formation
1. Causes oxidative deamination of £ amino group of lysine to allysine.
2. Allysine = lysine with aldehyde group.
3. These aldehydes react with £ amino group of unoxidized lysine or hydroxyl lysine forming intra and intermolecular covalent cross links.
37
Causes of osteogenesis imperfecta (brittle bone syndrome)
Replacement of glycine by amino acid with bulky side chain.
38
Effects of osteogenesis imperfecta
The abnormal chain prevents the formation of the require triple helical conformation.
39
Osteogenesis imperfecta manifestations
ELPS
1. Easily fracture of bones.
2. Loose joints.
3. Poor muscle tone.
4. Slight spinal curvature.
40
Elastin
Rubber like protein.
41
Elastin site
1. Ligaments.
2. Wall of blood vessels.
3. Lungs.
42
Elastin unit
Tropoelastin
43
Elastin characters
1. Insoluble in water (composed mainly of non-polar amino acids like glycine and alanine).
2. Contains little Hydroxyproline and no hydroxylysine.
3. Fibrillin (glycoprotein in ECM) acts as a scaffold for disposition of elastin.
44
Elastin structure
1. Tropoelastin is secreted into extracellular space.
2. Some Tropoelastin chains are connected through their lysine residues.
3. Some lysyl residues are oxidatively deaminated by lysyl oxidase forming allysine.
4. 3 allysine residues interact with 1 unoxidized lysine residue to form desomosine.
5. Elastic properties of elastin is due to formation of desomosine.
45
Elastin shape
1. Fibrous: extended.
2. Relaxed: globular.
3. Stretches in different directions.
46
a-1 anti trypsin deficiency other names
a-1 proteinase inhibitor deficiency: it inhibits many proteases like elastase.
47
a-1 anti trypsin deficiency mechanism
Bacterial infection causes acute inflammation while the body reacts through acute inflammation while the body reacts through acute inflammatory cells, which secretes proteinases like trypsin and elastase.
48
Importance of a-1 anti trypsin
1. Protects tissues from elastase enzymes of inflammatory cells especially neutrophils.
2. It’s concentration rises markedly in acute inflammation.
49
a-1 anti trypsin deficiency
Neutrophil elastase breaks down elastin which damages lung elasticity. This causes respiratory complications like: ECC
1. Emphysema.
2. COPD (Chronic obstructive pulmonary disease).
3. Cirrhosis of liver in adults and children.
50
Fibronectin characters
One of the major proteins of ECM.
51
Fibronectin structure
1. 2 identical subunits joined by 2 disulfide bonds.
2. Has several binding sites for:
- Heparin.
- Collagen.
- cell surface receptors (integrins).
52
Fibronectin functions
Adhesive characters.
53
Integrin
1. Transmembrane adhesion receptors.
2. Integrin receptors interact with:
- Extracellular proteins: Fibronectin and collagen.
- Intracellular proteins: actin.
3. Through these reactions the exterior and interior of the cell can communicate.
54
Fibrillin characters
Glycoprotein secreted by fibroblasts in ECM.
55
Fibrillin sites
Suspensory ligaments of lens and aorta.
56
Fibrillin functions
Forms a scaffold for disposition of elastin.
57
Marfans syndrome cause
1. Mutation in the gene coding for Fibrillin.
58
Marfan’s syndrome manifestations
1. Dislocation of lens (ectopic lentis).
2. Dilatation of the aorta.
3. Hyper extensibility of joints.
4. Patient is always tall with long digits.
59
Cartilage proteins
Cartilage is avascular CT (nutritionby diffusion and osmosis).
60
Cartilage proteins
1. Collagen proteins.
2. Non collagenous proteins.
61
Collagen proteins
1. Collagen type II: 98% of total collagen in cartilage.
2. Minor forms of collagen:
V, VI, IX, X, XI
62
Non collagenous proteins
1. Proteoglycans (aggrecans): major proteoglycan of cartilage.
2. Large non aggregating proteoglycans.
3. Chondronectin: binds type II collagen.
63
Bone proteins
Bone is mineralized connective tissue.
64
Bone protein types
1. Collagen proteins.
2. Non collagenous proteins
65
Collagen proteins bone proteins
1. Type I collagen: 90% of total collagen in bone.
2. Collagen type V.
66
Non collagenous proteins bone
1. Osteocalcin.
2. Proteoglycans.
3. Osteonectin.
67
Osteocalcin
1. Synthesized by osteoblasts.
2. Major non collagenous matrix protein.
3. Calcitriol (active vit.D) induces it’s synthesis.
4. Vitamin K mediates carboxylation of glutamate residues to y carboxy glutamate that can bind Ca.
5. It’s serum level is used as a marker for new bone formation.
68
Bone Proteoglycans
Important for bone development and mineralization.
69
Osteonectin
Glycoprotein that binds collagen and important for bone mineralization.
70
Osteoporosis
Progressive reduction in bone mass or density causing weakness.
71
Osteoporosis effects
Bone becomes brittle and easy to fracture.
72
Risk factors of osteoporosis
AFFSIDL
1. Aging.
2. Female gender.
3. Family history.
4. Sedentary life.
5. Intake of caffeine or soda.
6. Drugs as corticosteroids help in osteoporosis.
7. Low intake of Vitamin D, Ca, magnesium, and P.
