Tissues 3 Flashcards
What does extracellular matrix surround?
Connective tissue
What is extracellular matrix.
Complex network of proteins and carbohydrates
What are the functions of the ECM?
- Physical Support
- Determines mechanical and physiochemical properties
- Influences growth, adhesion and differentiation status
- Essential for development, tissue function and organogenesis.
What are the components of connective tissues?
- Collagens
- Glycoproteins
- Proteoglycans
(cellular component)
Types I-III collagen are?
Fibrillar
Type 4 collagen is present where?
In the basement membrane (basal lamina)
Give examples of glycoproteins.
- Fibronectin
- Fibrinogen
- Laminins (in basement membrane)
Give examples of proteoglycans.
- Aggrecan
- Versican
- Decorin
- Perlecan (in basement membrane)
How can matrix proteins be affected?
Gene mutations
Name 5 diseases arising from matrix proteins being affected.
- Osteogenesis imperfecta - Type 1 Collagen
- Marfan’s Syndrome - Fibrillin 1
- Alport’s syndrome - Type IV collagen (a5)
- Epidermolysis bulls - Laminin 5
- Congenital Muscular Dystrophy - Laminan 2 (a2)
Diseases arising from ECM metabolism being affected?
Hurler’s Syndrome - L-a-iduronidase
Other micopolysaccharidioses
What causes fibrotic disorders?
Excess ECM deposition
Name some fibrotic disorders.
Liver fibrosis - cirrhosis
Kidney fibrosis - diabetic nephropathy
Lung fibrosis - silicosis
Disorders due to excessive loss of ECM?
Osteoarthritis
What are collagens?
Family of fibrous proteins - found in all multicellular organisms
Major proteins of bone, tendon and skin
What is the most abundant protein in mammals?
Collagen
How are collagen fibrils arranges in skin?
Why?
Successive layers are perpendicular to each other (same as in bone and cornea).
Resists force in all directions. Gives tissues tensile stress.
How many known types of collagen are there?
28
How many alpha chains comprise a collagen?
- Forms a triple helix
How many genes form Type 1 Collagen?
2 genes
Which types of collagen are homotrimeric?
Type 2 and 3
They have the same a chain
How many genes code for collagen?
42.
Every 3rd amino acid residue in the a chain is?
A glycine.
Why does the glycine face the interior of the polypeptide chain?
It is hydrophobic.
Smallest amino acid so can fit in the gap
Collegen is a stiff triple helical structure?
True
What is the characteristic of the collagen a-chain?
Consists of a repetitive pattern.
X, Y, Glycine.
X is often proline
Y is often hydroxyproline
In fibrillar collagens, how many amino acid residues long are the a-chains?
1000.
How do collagen molecules form a collagen fibril?
By associating laterally.
What do collagen fibrils form to make?
Collagen fibres, visible to naked eye
Where are the non-collagenous domains located in newly synthesised collagen chains?
At the N and C terminals
What happens to the non-collagenous domains after secretion?
They are removed.
What do the N and C terminals of the pro collagen have?
Globular proteins associated
How are the globular proteins associated to procollagen cleaved?
Peptidase cleaves them off
Some collagen types retain globular ends
How are the hydrogen bonds formed between collagen fibrils?
Cross links are formed between adjacent collagen fibres
Explain the biosynthesis of collagen.
- Procollagen synthesised.
- Hydroxylation (selected Prolines and Lysines)
- Glycolysation of certain hydroxylysines.
- Self assembly of 3 pro -a-chains
- Procollagen triple helix formation
- Secretion
- Cleavage of pro-peptides
- Self assembly into fibril
- Aggregation of fibrils to form fibre.
Why hydroxylate lysine and proline in collagen biosynthesis?
Hydroxylation contributes to hydrogen bond cross link formation
How are proline and lysine hydroxylated?
Hydroxylated by prolyl and Lysyl hydroxylases
What do prolyl/lysyl hydroxylases require?
- Vitamin C
2. Fe(2+) (Post translational modification)
How is scurvy caused?
- Underhydroxylated collagens.
- Lack cross links, less stable collagen
- Tissues less stable
What happens to hydroxylysine and hydroxyproline after secretion?
Undergoes further modification - forms covalent cross links.
Why do tendons have tensile strength in one direction?
They have parallel collagen fibres?
How are collagen fibres arranged?
In a staggered array.
Do all collagens form fibrils?
NO
What do types 9 and 12 collagens do?
Associate with fibrillar collagens and regulate their organisation.
Which collagen is a network forming collagen and is present in all basal laminae (by assembling into a sheet-like network)?
Type 4
What do elastic fibres do?
They give structures elasticity.
How is the extent of stretching limited?
Collagen and elastic fibres are interwoven
What are elastic fibre cores made up of?
Microfibrils and proteins
Microfibrils rich in protein fibrillin
How is Marfan syndrome caused?
Fibrillin I mutations.
What does elastic fibre integrity depend on?
Depends on microfibrils containing fibrillin,
What happens in patients with Marfan’s?
Elastic fibres lack integrity - overly stretched
What are Marfan’s patients more susceptible to?
CVS problems.
They are tall and slender.
What are the 2 segments that make up elastin?
- Hydrophobic regions
- a-helical chains (rich in alanine and lysine)
Many lysine side chains are cross linked
What are basement membranes/basal laminae?
Flexible, thin mats of ECM that underlie Epithelial sheets and tubes
Highly specialised
What do basal laminae surround?
Muscle, peripheral nerve and fat cells
Give a use of ECM.
Filter for macromolecules, acting as a highly selective filter
What is diabetic nephropathy?
- ECM accumulation
- Causes thick kidney glomerulus
- Thicker basement membrane
- Causes restricted renal filtration as capillaries are impinged.
