Tissues 3 (ECM) Flashcards
Define extracellular matrix
Complex network of proteins and carbohydrates which forms the insoluble component of the extracellular environment
What are the three main components of the ECM?
- collagen
- multi-adhesive glycoproteins
- proteoglycan
Which ECM substances are only found in the basement membrane?
- collagen type IV
- laminin
- perlecan
A mutation in type 1 collagen causes what disease?
Osteogenesis Imperfecta
What is an example of a disease that affects ECM catabolism and the protein affected?
Hurler’s Syndrome: L-alpha-iduronidase
What diseases are caused by excess deposition of ECM?
- lung fibrosis
- liver fibrosis
- cirrhosis
- kidney fibrosis
What disease is caused by excessive loss of ECM?
osteoarthritis
What is the arrangement and significance of collagen fibres in skin?
- successive layers at right angles to each other
- can resist tensile force in all directions
What is the structure of a collagen molecule?
- stiff triple helix (three alpha chains)
- every third AA is glycine (small enough to fit in the inside helix)
- other two AAs commonly proline and hydroxyproline
Describe the biosynthesis of collagen.
- produced in fibroblasts
- pro-collagen (with two propeptides - N&C - at each end not in triple helical form)
- propeptides cleaved outside cell
- collagen able to form cross-linkages with other collagen molecules to form fibrils
What is the importance of hydroxylation of proline and lysine in collagen structure?
- allows interchain hydrogen bonding (contributes to the structural integrity and stability of the collagen fibre)
- lysine and hydroxylysine modified in formation of covalent cross-linkages after the collagen is secreted (provides tensile strength and stability)
What two substances are needed for hydroxylation of proline and lysine?
- vitamin C
- iron
What are the collagens that don’t form fibrils?
- fibril-associated collagens (e.g. collagen IX) involved in organisation and size of collagen fibrils
- network forming collagens (e.g. collagen IV - basal lamina)
What is the composition of elastic fibres?
- elastin core
- microfibrils around outside (rich in fibrillin)
What are some clinical features of Marfan’s Syndrome?
- longer arm span than height
- long fingers and toes
- predisposed to aortic ruptures
What is the general structure of elastin?
- hydrophobic region
- alpha-helical region
- regions alternate along polypeptide chain
What is connective tissue?
- ECM + component cells (macrophages)
What are the collagen types?
- fibrillar: I, II, III
- non-fibrillar: IV (basement membrane)
What are type of glycoproteins?
- fibronectin
- fibrinogen
- laminins (basement membrane)
What are the types of proteoglycans?
- aggrecan
- versican
- decorin
- perlecan (basement membrane)
A mutation in fibrillin 1 causes what disease?
Marfan’s Syndrome
A mutation in type 4 collagen causes what disease?
Alport’s Syndrome
A mutation in laminin 5 (all three chains) causes what disease?
Epidermolysis bullosa
A mutation in laminin 2 (alpha 2 chain) causes what disease?
Congenital Muscular Dystrophy
