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
How are collagen fibrils laid down?
parallel to eachother (gives tensile strength)
What type of helix do fibrillar collagens form?
left handed (from 1000 AAs)
What enzyme cleaves procollagen to collagen?
extracellular peptidases
Which enzymes does hydroxylation use?
prolyl & lysyl hydroxylases
What is basal lamina?
- special type of ECM
- thin, flexible mats of ECM
- underlies epithelial sheets and tubules
