Tissues 3: Extracellular matrix biology I Flashcards
Define Extracellular Matrix
The ECM is a complex network of proteins and carbohydrates deposited by cells which form the insoluble part of the extracellular environment.
List the functions of the Extracellular Environment
Provides physical support
Determines the mechanical and physicochemcial properties of the tissue
Influences the growth, adhesion and differentiation status of the cells and tissues with which it interacts
Essential for development, tissue function and organogenesis
PIED
Explain the relationship between ECM and Connective tissue
Connective Tissue= extracellular matrix + component cells Connective tissues are tissues rich in ECM add pic
List the major components of the ECM
Collagens, Multi-adhesive glycoproteins and Proteoglycans
Recall examples of human disorders resulting from ECM pathology which are due to gene mutations affecting the matrix proteins
Include the proteins that are affected by the disease
osteogenesis imperfecta - Type I collagen
Marfan’s syndrome - Fibrillin 1
Alport’s syndrome - Type IV collagen
Epidermolysis Bullosa - Laminin 5 (in all 3 chains) Congenital
Muscular Dystrophy- Laminin 2 (2 chain)
What protein is effected by osteogenesis imperfecta
Type I collagen
What protein is effected by Marfans syndrome
Marfan’s syndrome - Fibrillin 1
What protein is effected by Alports syndrome
Type IV collagen
What protein is effected by Epidermolysis Bullosa?
Laminin 5 (in all 3 chains) add pic
What protein is effectedd by Congenital Muscular Dystrophy?
Laminin 2 (alpha 2 chain)
Recall examples of human disorders resulting from ECM pathology which are due to gene mutations affecting ECM catabolism.
Include the proteins that is effected by the disease.
Hurler’s syndrome - L-alpha-iduronidase add pic
List examples of Fibrotic disorders due to excessive ECM depositin
Liver fibrosis - cirrhosis Kidney fibrosis - diabetic nephropathy Lung fibrosis - silicosis
Name an example of a disorders due to excessive loss of ECM
osteoarthritis
What is collagen composed of an what is its structure
Each collagen molecule comprises three alpha chains, forming a triple helix.
How many different alpha chains are the following types of collagen made up off? Type 1 Type 2 Type 3
Type I collagen has chains from two different genes -pro-alpha1(I) chain and also with a pro-alpha2(I) chain Types II and III collagen have only one chain type –
What amino acid occupies every third position in a collagen triple helix
Glycine
Why does Glycine occupy the 3rd position in a collagen triple helix
every third position must be occupied by glycine, as this is the only amino acid small enough to occupy the interior.
What is the molecular composition (what amino acids make up collagen) and structure of collagen?
Characteristic gly-x-y repeat: x is often proline, y is often hydroxyproline Left handed triple helix add pic
Explain the biosynthesis of collagen
1) Synthesis of PRO- alpha chain 2)Hydroxylation of Selected Prolines and Lysines 3) Glycosylation of Selected Hydroxylysines 4)Self-Assembly of Three PRO- alpha chains 5) Procollagen Triple-Helix Formation 6) Secretion 7) Clevage of Propeptides 8) Self -Assembly into Fibril add pic
What happens to lysine and proline during collagen synthesis
Hydroxylation
Why does proline and lysine get hydroxylated
Contributes to interchain hydrogen bond formation. - increase tensile strength
What role does Vitamen C play in Callogen synthesis and what effect does a lack of vitamen C cause?
Prolyl and lysyl hydroxylases require Fe2+ and vitamin C Vitamin C-deficiency results in underhydroxylated collagens, with dramatic consequences for tissue stability (scurvy). add pic
Name a non-fibrillar type of collagen
Type IV collagen
Where is type IV collgen found?
Basement Membrane Type IV collagen is a network-forming collagen and is present in all basement membranes, though its molecular constitution varies from tissue to tissue. add pic
What is collagen important for?
Important for tensile stength of tissue
Define elastic fibres
elastic fibres are important for the elasticity of tissues
What is the composition of elastic fibres
Elastic fibres consist of a core made up of the protein elastin, and microfibrils, which are rich in the protein fibrillin. add pic
Name a disorder of elastic fibres and why is it a disorder of elastic fibres?
Marfan’s syndrome Marfan syndrome is a mutation in fibrilin-1 which is a part of microfibrils
Define Basement Membrane
Basement membranes (BMs; also called basal laminae) are flexible, thin mats of extracellular matrix underlying epithelial sheets and tubes
What is the main components of the Basement membrane?
Collagen type IV Laminins
Name the functions of basement membrane
Separation of cells from underlying connective tissue.
In the kidney glomerulus, the BM acts as a highly selective filter. add pic
