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ecm Flashcards

1
Q

what is the extrcelullar matrix

A

complex network of proteins and carbohydrates filling spaces between cells
comprises both fibrillar and non-fibrillar components

fibrillar meaning fibre making

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2
Q

functions of ECM

A

Provides physical support

influences the growth, adhesion and differentiation status of the cells and tissues with which it interacts

Essential for development, tissue function and organogenesis

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3
Q

connective tissue companonets

A

ECM and component cells
collagen
multi adhesive glycoprotien
ptoteoglycans

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4
Q

connective tissue examples

A

Tendon n skin - tough flexible

Bone: hard and dense

Cartilage: resilient and shock-absorbing

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5
Q

disorders from ECM

A
  1. Gene mutations affecting matrix proteins
  2. Gene mutations affecting ECM catabolism
  3. Fibrotic disorders due to excessive ECM deposition
  4. Disorders due to excessive loss of ECM
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6
Q

what is collagen

A

fibrous protein, strcutural protein

resist tensile force

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7
Q

where is collagen found commanly

A

bone, tendon and skin

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8
Q

alignment of collagen in skin

A

succesive layers at nearly right angles

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9
Q

mature bone and cornea collagen alignment

A

same arrangemnet

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10
Q

structure of collagen

A

three α chains, forming a triple helix. homo or hetrotrimers
can be different a chain

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11
Q

how many genes does type 1 collagen have

A

two different genes - its composition is [α1(I)]2 [α2(I)]

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12
Q

how many genes do type 2 and 3 have

A

one chain type – their compositions are, therefore, [α1(II)]3 and [α1(III)]3

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13
Q

what is every 3rd amino acid and why

A

glycine- because smallest aa small r group of just h

small enough to fit in stiff structure

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14
Q

x and y are commonly what

A

x is often proline, y is often hydroxyproline

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15
Q

forming a collagen fibre

A

a chain
3 a chain
collagen fibril
collagen fibre

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16
Q

what are newly synthesised collagen chains called and what do they have

A

pro-collagen
have n and c terminal propeptide
n and c mean non collagenous

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17
Q

when are the n and c domains removed

A

domains are removed after secretion

but if it stays in the cell it is kept

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18
Q

fibrillar collagen biosynthesis

A

1) synthesis of pro a chain
2) hydroxylation of some prolines and lysines
3) glycosylation of some hydroxylysines
4) self assemble of pro a chain
5) formation of procollagen triple helix
6) secreted
7) cleave propeptide
8) self assemble into fibril
9) aggregation of collagen to collagen fiber

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19
Q

cross linking why

A

tensile strength and stability

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20
Q

what aa are involved

A

lysine and hydroxy lysine

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21
Q

what lysine and proline hydroxyaltion

A

fe2+ and vitimin c
contribute to hydrogen bond formation
modified in formation of covalent crosslinkages

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22
Q

what does vitiman c result in

A

underhydroxylated collagens

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23
Q

ehlers danlos syndrome EDS

A

inheritied connective tissue disorder causes stertchy sin and loose joints

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24
Q

what disorder arises from EDS

A

mutation of collagen affecting collagen production structure and processing

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25
Q

what are the fibrin associated collagens

A

type 9 and 12

regulate organisation of collagen fibrils

26
Q

what is the function of type 4 collagen

A

network forming collagen
present in all basement membranes
more flexible
helix is disorded so they’re bendy

27
Q

how are the type 4 collagens assembled

A

n and c terminals not removed

n terminals interacts forming a network and self assemble to form an aggregate

28
Q

what are basement membranes

A

flexible, thin mats of extracellular matrix underlying epithelial sheets and tubes
highly specialised extracellular matrices containing a distinct collection of collagens, glycoproteins and proteoglycans.

29
Q

function of basement membrane in kidney

A

forms Glomerular basement membrane

30
Q

what happens in diabetic nephropathy

A

accumulation of extracellular matrix leading to a highly thickened basement membrane –> This restricts renal filtration and can lead to renal failure.

31
Q

what is alport syndrome

A

mutations in collagen IV result in an abnormally split and laminated GBM which is associated with a progressive loss of kidney function and also hearing loss.

32
Q

where are basemant membranes typically found

A

surround muscle, peripheral nerve and fat cells and underlie most epithelia.

33
Q

function of elastic fibres

A

elasticity of tissues, such as skin, blood vessels and lung

34
Q

what makes up elastic fibres

A

protein elastin, and microfibrils and fibrilin

35
Q

mutation in fibrilin 1

A

marfans disorder, involves

skeletal, ocular, and cardiovascular systems

36
Q

what does marfan syndrome cause

A

arachnodactyly (spider-like fingers).

37
Q

segments of elsatin

A

hydrophobic and a helical regions rich in alanine and lysine

38
Q

what are lamins made of

A

proteins made up of an α chain, a β chain and a γ chain

39
Q

what is the functions of lamin

A

multi-adhesive proteins
interact with a variety of cell surface receptors

They can self-associate as part of the basement membrane matrix

interact with other matrix components

40
Q

mutations in lamin chains examples

A

muscular dystrophy and epidermolysis bullosa

41
Q

what causes muscular dystrophy

A

absence of the α2 chain in laminin 2

42
Q

symptoms of it

A

hypotonia (abnormally decreased muscle tension), a generalised weakness and deformities of the joints.

43
Q

how fibronectins exist

A

insoluble fibrillar matrix or as a soluble plasma protein

44
Q

what are fibronectins

A

multi-adhesive proteins

45
Q

functions of fibronectins

A

interact with cell surface receptors and other matrix molecules
regulating cell adhesion and migration
wound healing and promote blood clotting

46
Q

what are proteoglycans

A

core proteins to which are covalently attached one or more glycosaminoglycan (GAG) chains.

47
Q

What are GAG made up of

A

repeating disaccharide units
with one or 2 sugars being amino sugar
when the oh group is swapped for amine group

48
Q

why are GAG carry high negative chrage

A

sulfated or carboxylated

49
Q

cartilage

A

matrix rich in collagen with large quantities of GAGs

50
Q

what is hyularonan

A

a GAG chain

51
Q

where is it found

A

soft connective tissue

52
Q

structure

A

a carbohydrate chain with no core protien

53
Q

polymerisation of hyularanon

A

high degree of polymerization
large volume
high viscousity

54
Q

role of hyularonan

A

protects the cartilage surface from damage

55
Q

what is aggrecan

A

major constituent of the cartilage extracellular matrix.

56
Q

how are the GAG in aggrecan

A

highly sulfated, increasing their negative charge. Also present are large numbers of negatively carboxyl group

57
Q

why it is negative

A

to attract na+ so water can be retained

under compression water is given up but gained when load is reduced

58
Q

osteoarthirits

A

erosive disease resulting in excessive extracellular matrix degradation.

59
Q

what happen in …

A

cartilage over the end of bones are lost\

aggrecan is cleaved

60
Q

what are fibrotic diseases

A

excessive production of fibrous connective tissue.

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