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MCB1 Block 3 > ECM > Flashcards

ECM Flashcards

1
Q

What are the two major fibers in the ECM?

A

collagen & elastin

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2
Q

Basal lamina is a special type of ____

A

ECM

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3
Q

Anything below basal lamina is the:

A

Dermis

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4
Q

What are embedded in the proteoglycan gel?

A

fibers

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5
Q

What does fibronectin bind to?

A

integrin & collagen

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6
Q

What is the function of collagen?

A

strengthens, resists stretching, organizes ECM

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7
Q

What is the function of elastin?

A

elasticity

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8
Q

What is fibrillin?

A

a protein required for assembly of elastic fibers

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9
Q

What is the function of fibrillin?

A

forms a protein coat around elastic fibers, its required for assembly of elastic fibers

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10
Q

Besides collagen and elastin, what major substance is in the ECM?

A

Ground substance

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11
Q

What is the function of ground substance?

A

hydrated gel, resists compressive forces, permits rapid diffusion of nutrients, metabolites & hormones between blood & tissue

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12
Q

What two major substances are found in ground substance?

A

proteoglycans

glycoproteins

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13
Q

What composes proteoglycans?

A

Mostly GAGs and a little protein

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14
Q

What is the function of proteoglycans?

A

resist compression & fill spaces

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15
Q

What composes glycoproteins?

A

Mostly protein, a little GAGs

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16
Q

What is the function of glycoproteins?

A

Adhesive glycoproteins

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17
Q

What are three major glycoproteins in ECM?

A

fibronectin, laminin, entactin

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18
Q

Corneal & stroma ECM is transparent - why?

A

fibers are arranged in parallel bundles

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19
Q

How is ECM arranged in bone & teeth? (very generally)

A

its calcified

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20
Q

How is ECM arranged in tendons? (very generally)

A

ropelike

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21
Q

How is ECM arranged in cartilage? (very generally)

A

lots of collagen with ground substance - to absorb shock

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22
Q

Name the 5 functions of fibrous proteins

A

Fibrous proteins have physical properties that impart strength or flexibility

Simple repeating element of secondary structure

Water insoluble (hydrophobic residues packed in center)

Extracellular, long-lived proteins

Used to construct connective tissue, tendons, bone matrix

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23
Q

Collagen is what percentage of our proteins?

A

25%

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24
Q

What is the structure of collagen?

A

Thee collagen alpha chains wind together to form a triple helix

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25
Q

How is collagen arranged in skin?

A

loosely woven, arranged in all directions for support no matter which way skin is pulled

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26
Q

Every third aa of the alpha chain that makes collagen is made of what?

A

glycine

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27
Q

Why is it important that glycine is arranged every 3rd aa in alpha chain for collagen?

A

allows tightly packed triple helix (glycine is small), allows for hydrogen bonding w/ adjacent helix

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28
Q

How is collagen arranged in tendons?

A

parallel bundles

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29
Q

What cell makes collagen?

A

fibroblasts & epithelial cells

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30
Q

What is the only type of collagen found in basal lamina?

A

Type IV

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31
Q

Besides glycine, what aa is found on alpha helix of collagen?

A

proline & lysine

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32
Q

What often happens to the proline and lysine on the aa of alpha chain of collagen?

A

it is hydroxylated

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33
Q

Why is there hydroxyproline & hydroxylysine on alpha helix of collagen?

A

allows more hydrogen bonds b/w alpha chains, more stability

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34
Q

What is significant about the triple helix structure of collagen?

A

like cables of suspension bridge, very strong, resists unwinding

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35
Q

What is preprocollagen?

A

alpha chain (collagen) with ER signal sequence with propeptide domain at C & N terminus

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36
Q

What is the name of the alpha chain that will become collagen before it enters the ER?

A

preprocollagen

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37
Q

What does the “pre” mean in preprocollagen

A

it has an N terminal signal sequence to direct it to the rER for synthesis

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38
Q

What does preprocollagen become?

A

procollagen

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39
Q

What takes off the ER signal sequence from the preprocollagen?

A

signal peptidase

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40
Q

Type I collagen has how many alpha 1 chains and how many alpha 2 chains?

A

2 alpha 1 chains

1 alpha 2 chain

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41
Q

What does the “pro” mean in procollagen?

A

peptide domains @ C & N terminus

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42
Q

Three procollagen alpha chains assemble together to form a triple helix, where does this occur?

A

ER

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43
Q

Where do disulfide bonds form on propeptides?

A

C terminus

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44
Q

Where and when are propeptide domains cleaved off of procollagen?

A

Propeptide will be joined in ER, then go to golgi, then excreted into ECM. then the propeptide domain will be cleaved off.

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45
Q

Where are collagen fibers formed?

A

In ECM after propeptide domain cleaved, they will spontaneously join and form large fibers

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46
Q

What is the function of the propeptide domain on procollagen?

A

prevents associtaion of collagen fibril forming inside cell (its too big for cell!), helps form helix

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47
Q

What happens to some hydroxylysines inside the ER?

A

they are glycosylated

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48
Q

Where are disulfide bonds formed on procollagen in ER?

A

C terminus

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49
Q

What is the function of the disulfide bonds in procollagen?

A

helps align the alpha chains, initiates triple helix formation, kind of acts like a zipper to bind the helixes

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50
Q

The disulfide bonds have what’s called a “zipper mechanism” where they help join alpha chains to form helix - describe the zipper mechanism

A

“zips” up the three chains starting at C terminus and going to N terminus

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51
Q

Hydroxyproline is only found in what two places?

A

Collagen & elastin

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52
Q

The enzymes that convert proline and lysine to hydroxyproline & hydroxylysine require what?

A

ascorbic acid (vitamin C) and iron

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53
Q

What is ascorbic acid?

A

Vitamin C

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54
Q

What are the three enzymes we need to know that convert proline & lysine to hydroxyproline & hydroxylysine?

A

Prolyl-3-hydroxylase
Prolyl-4-hydroxylase
Lysyl hydroxylase

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55
Q

What happens if there is a lack of hydroxyproline?

A

decreased stability of triple helix in collagen

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56
Q

What happens if there is no hydroxyproline in collagen?

A

collagen loses almost all of its helical content

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57
Q

Key words: anemia, fatigue, bleeding gums is what disease?

A

scurvy

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58
Q

Characteristics: Bleeding gums, loosened teeth, petechiae (pinpoint hemorrhages around air follicles, gums, nails); ecchymoses, poor wound healing, poor bone development, anemia & fatigue are what disease?

A

Scurvy

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59
Q

What is the mechanism for scurvy?

A

Vit C is required for hydroxylationof proline & lysine; deficiency of Vit C → lack of hydroxyproline → no H bonds → decreased stability of collagen triple helix → weak CT

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60
Q

What is the mode of inheritance for scurvy?

A

Acquired

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61
Q

Where is the defect in scurvy?

A

Vitamin C (ascorbic acid) deficiency; unstable collagen

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62
Q

How long does it take for a person not eating any vitamin C to see symptoms of scurvy and why?

A

20-40 days, remodeling of CT takes time

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63
Q

What removes the propeptides on procollagen once it is excreted into the ECM?

A

peptidases

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64
Q

Why do propeptides need to be removed from collagen?

A

so that the collagen can form add’l bonds and cross link

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65
Q

What kind of interactions stabilize the collagen fibrils?

A

covalent

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66
Q

What aa is often on the end of collagen?

A

lysine

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67
Q

Lysines (and hydroxylysines) convert into what on collagen?

A

aldehydes

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68
Q

What converts lysines (and hydroxylysines) into aldehyde?

A

lysyl oxidase

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69
Q

Why are lysines converted to aldehydes?

A

So they can covalently bond to other collagen fibers

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70
Q

What is the function of aldehydes on collagen fibers?

A

Aldehydes react spontaneously
→ covalent bonds with each other or other lysines or hydroxylysines
Usually at ends
Stabilise side-by-side packing

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71
Q

What are the different types of fibrillar collagen?

A

Type I, II, III, V

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72
Q

What are the different types of FACIT collagen?

A

Type VI, IX, XII

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73
Q

What does FACIT stand for?

A

Fibril-Associated Collagens (VI, IX, XII) with Interrupted Triple helices

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74
Q

What are the different types of sheet (networking)-forming collagen?

A

Type IV, X

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75
Q

What are the different types of anchoring fibrils?

A

VII

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76
Q

Type I, II, III, V belong to which collagen family?

A

Fibrillar

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77
Q

What type of collagen is the only one found in the basal lamina?

A

Type IV (Sheet-forming collagen)

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78
Q

Where are anchoring fibrils found?

A

They anchor the basal lamina to the interstitial matrix

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79
Q

Type VI collagen binds and links what type of fibril?

A

Type I

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80
Q

Type IX collagen binds and links what?

A

bind & link type II fibrils & bind chondroitin sulfate (GAG)

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81
Q

Key words: hyperextensible skin, hypermobile joints, fibrillar collagen is what disease?

A

Ehlers-Danlos Syndrome

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82
Q

Characteristics: Hyperextensible fragile skin, joint hypermobility & dislocations is what disease?

A

Ehlers-Danlos Syndrome

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83
Q

What is the mechanism for Ehlers-Danlos Syndrome?

A

Defected fibrillar collagen synthesis → improper assembly of collagen → connective tissue weakness

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84
Q

Where is the defect in Ehlers-Danlos syndrome?

A

Defected collagen (fibrillar collagen – I, III, V) synthesis

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85
Q

What coats the surface of fibrillin collagen and helps them bind together and to other components?

A

FACIT

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86
Q

____ is more flexible than fibrillar colalgen

A

FACIT

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87
Q

After it is secreted, what part of ECM retains its propeptides?

A

FACIT

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88
Q

Describe the structure of FACIT

A

3 stranded structure interrupted by non-helical domains, the non-helical domains cause kink

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89
Q

What two enzymes allow for the degradation of collagen?

A

MMP-1 & MMP-2

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90
Q

Why is it important to have enzymes to degrade the collagen in ECM

A

for remodeling, to help cells move, to help heal

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91
Q

What does MMP stand for?

A

Matrix Metalloproteinases

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92
Q

What is another name for MMP-1?

A

Collagenase I

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93
Q

What is another name for MMP-2?

A

Collagenase IV

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94
Q

What does MMP-2 degrade?

A

Type IV collagen → basal lamina

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95
Q

What type of cell is MMP-2 overexpressed

A

cancer cells (esp. epithelial cancer)

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96
Q

How are MMPs present in the ECM?

A

they are zymogens

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97
Q

What is a zymogen

A

Inactive enzyme

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98
Q

How does the body activate the MMPs that are inactive zymogens?

A

cleaved and activated

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99
Q

MMP can be stored where?

A

ECM

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100
Q

What is an inhibitor of MMP?

A

TIMPs

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101
Q

What is the dominant ECM protein in arteries?

A

elastin

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102
Q

What tissues have a lot of elastin?

A

arteries, skin, lungs, uterus

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103
Q

What amino acids are often in elastin?

A

glycine & proline

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104
Q

Collagen has glycine and proline like elastin - what is the difference in terms of these aa in elasin?

A

they will not be glycosylated and there is no hydroxylysine

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105
Q

Collagen fibers are often interwoven with what to prevent tearing and limit stretching?

A

elastic fibers

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106
Q

How is elastic tissue in relaxed state attached? (aka what type of bond)

A

covalently

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107
Q

tropoelastin molecules spontaneously assemble to form what?

A

elastic tissue

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108
Q

What is the main glycoprotein that covers elastin core?

A

fibrillin

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109
Q

If there is a mutation in fibrillin what is the disease?

A

marfan syndrome

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110
Q

What does fibrillin bind to?

A

elastin

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111
Q

what forms a scaffold for deposited elastin?

A

microfibrils

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112
Q

What is fibrillin essential for?

A

assembly & integrity of elastic fibers

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113
Q

Characteristics: Aortic root dilation & dissection, lens subluxation & retinal detachment, tall & thin, long limbs & fingers – archnodactylyl, funnel chest – pectus excavatum is what disease?

A

Marfan syndrome

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114
Q

What is the mechanism for marfan syndrome?

A

Defect in fibrillin → weak elastic tissue

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115
Q

What is the mode of inheritance for marfan syndrome?

A

AD

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116
Q

Where is the defect for marfan syndrome?

A

Defect in fibrillin (elastin)

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117
Q

What can happen to the aorta in a person who has marfan syndrome?

A

blood going through aorta with high pressure, can rupture part of wall and create false lumen

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118
Q

What does arachnodactyly mean?

A

long limbs & fingers

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119
Q

What does pectus excavatum mean?

A

funnel chest

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120
Q

What enzymes allows degradation of elastin?

A

elastase

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121
Q

Lungs inhibit what enzyme so there is no degeneration of its elasticity?

A

elastase

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122
Q

Why do the lungs need to inhibit elastase?

A

they cannot regenerate

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123
Q

What is the name of a serine protease secreted by neutrophils?

A

elastase

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124
Q

why do WBC need to secrete elastase?

A

so they can move through ECM

125
Q

What is an inhibitor of elastase?

A

α1-antitryspin

126
Q

α1-AT stands for what?

A

α1-antitryspin

127
Q

What secretes alpha1-AT?

A

liver

128
Q

key words: alpha1-AT, hyperventilation, respiratory distress, barrel chest are what disease?

A

emphysema/COPD

129
Q

Characteristics: Dyspnea, hyperventilation, hyper-inflated chest (barrel chest); develop emphysema by 30-50 years old (early if smoker) are what disease?

A

emphysema/COPD

130
Q

What is the mechanism for emphysema/COPD?

A

Deficiency of alpha1-AT → uninhibited destruction of elastic fibers by elastase → loss elastin in respiratory tissues → less flexible alveolus, stagnant alveolar air, respiratory insufficiency → respiratory distress; smoke inhibits alpha1-AT & recruits neutrophils to the lungs that released elastase (faster destruction in a smoker with deficiency) [Normally, elastase breaks down elastic fibers & it is inhibited by alpha1-antitrypsin]

131
Q

What is the mode of inheritance for emphysema/COPD?

A

AR

132
Q

Where is the defect for emphysema/COPD?

A

Deficiency of alpha1-antitrypsin (elastase)

133
Q

Cigarette smoke can cause irritation and inflammation in lungs as well as inhibit what?

A

α1-AT

134
Q

Describe how smoking could cause emphysema

A

Smoking inhibits alpha 1-AT and causes infections which promote neutrophils. Neutrophils release elastin and since there is no alpha1-AT to inhibit it, it will break down tissue. Lung tissue cannot regenerate

135
Q

Empysema is a form of:

A

COPD

136
Q

GAGs are covalently linked to a core protein to form what?

A

proteoglycan

137
Q

Hyaluraun, dermatan sulfate, chondroitin sulfate, keratin sulfate, heparin (heparan sulfate) are all examples of what?

A

GAGs

138
Q

What is the exception to the GAGs important esp. regarding proteoglycans

A

they are all sulphated except hyaluron

139
Q

Explain the difference b/w hyaluron and the other GAGs

A

hyaluron is not sulfated, it can associate with proteoglycans but cannot form a proteoglycan

140
Q

What can Hyaluronan associate with but not form?

A

proteoglycan

141
Q

GAGs all have what charge

A

negative

142
Q

How is the negative charge of GAGs important for the gelly like substance in ground substance?

A

the negative charge attracts a lot of water

143
Q

What is the biggest GAG?

A

Hyaluronan

144
Q

What is the only GAG that is made extracellularly?

A

Hyaluronan

145
Q

Where is Hyaluronan synthesized?

A

by enzyme on basal epithelial surface

146
Q

Why does Hyaluronan have to be synthesized extracellularly?

A

b/c it is too big to be made inside a cell

147
Q

What produced during wound healing and provides backbone for cells to migrate to for the healing?

A

Hyaluronan

148
Q

What is the lubricant of joint fluid? (What GAG)

A

Hyaluronan

149
Q

How much of vitreous humour is water?

A

99%

150
Q

How is so much of vitreous humour water?

A

It has a lot of proteoglycans and hyaluronan

151
Q

Proteoglycan can form large complexes with what?

A

hyaluronan

152
Q

Four sugars link GAG chain to what?

A

core protein

153
Q

How are GAGs attached to core protein?

A

covalently attached, linked to core protein by four sugars

154
Q

What kind of bond does hyaluronan use to bind to existing proteoglycans?

A

non-covalent

155
Q

The core protein has what kind of domain to bind to hyaluronan?

A

n-terminal hyaluronan binding domain

156
Q

What is aggrecan?

A

combination of hyaluronan assembling proteoglycans on its surface

157
Q

How do core proteoglycans associate with hyaluronic acid?

A

link proteins

158
Q

What forms the central core of aggrecan?

A

hyaluronic acid

159
Q

where will lots of aggrecan be found?

A

cartilage - it helps resist compression

160
Q

Describe the structure of aggrecan

A

a hyaluronan molecule attached to a bunch of core proteins (aggrecan) via linking proteins, there are a bunch of sulfates (like keratan sulfate & chondroitin sulfate) attached to the core protein

161
Q

What is another name for the core protein?

A

aggrecan

162
Q

Explain the function of proteoglycans as a porous hydrated gel in the ECM

A

Fills spaces: Occupy a large volume

Resists compression

163
Q

Expain the function of proteoglycans as a structural component of the ECM

A

Associate with eachother, collagen & basal lamina

164
Q

Explain how proteoglycans help with cell signaling in the ECM

A

Bind growth factors

Increase cell surface receptor binding affinity for the growth factors

165
Q

Explain how proteoglycans help with cell migration in the ECM

A

Create cell free space
Bind & regulate activity of proteases & their inhibitors
Immobilize chemokines (during inflammation)

166
Q

What type of collagen is found in basal lamina?

A

Collagen Type IV

167
Q

Basal lamina and above in skin is what?

A

epidermis

168
Q

Below basal lamina is what in skin?

A

dermis

169
Q

What collagen anchors the dermis to epidermis?

A

Collagen Type VII

170
Q

Components of basal lamina are secreted by what?

A

epithelial cells

171
Q

Interstitial cells are secreted by what?

A

fibroblasts or fibroblast type cells (chondrocytes, etc)

172
Q

What are the four components we need to know that make up the basal lamina?

A

Type IV collagen
Laminin
Entactin/Nidogen
HSPGs- perlecan

173
Q

What is another name for entactin?

A

Nidogen

174
Q

Basal lamina is a specialized:

A

ECM

175
Q

What does HSPG stand for?

A

heperan sulfate proteoglycan

176
Q

What are some specific cells the basal lamina surrounds?

A

skeletal muscle cells, adipocytes, schwann cells

177
Q

What important part of the kidney does the basal lamina play a huge role?

A

kidney glomerulus

178
Q

Why is the basal lamina so important in the kidney glomerulus?

A

forms permeability barrier, important for filtration

179
Q

What is attached to the basal lamina that binds to laminin?

A

integrin receptors

180
Q

What is an adhesive glycoprotein that attaches to cell receptors?

A

laminin

181
Q

What does laminin associate with in the basal lamina?

A

Type IV collagen
perlecan
nidogen

182
Q

What does type IV collagen bind to in basal lamina?

A

perlecan
nidogen
laminin

183
Q

What is not cleaved off of type IV collagen? and why?

A

propeptide domain is not cleaved off so it wont spontaneously form fibrils

184
Q

What is actually binding to the cells integrin receptors in basal lamina?

A

laminin

185
Q

What binds to form the scaffold for basal lamina?

A

laminin & type IV collagen

186
Q

What anchors the epithelial cells to the basal lamina?

A

laminin

187
Q

What are the names of the cell membrane laminin receptors that laminin binds to in the basal lamina?

A

integrins, dystroglycan

188
Q

What is the most prevelant part of the basal lamina?

A

laminin

189
Q

Laminin receptor binding (adhesion) promotes what?

A

cell growth & differentiation

190
Q

Where is perlecan found?

A

all basement membranes

191
Q

What is the function of perlecan?

A

mediates cell attachment to basal lamina for endothelial cells & fibroblasts; it anchors proteoglycan in matrix and increases its strength

192
Q

What does perlecan bind to specifically in basal lamina?

A

entactin, laminin, collagen IV & fibronectin

193
Q

What two HSPGs function in angiogenesis & mitogenesis?

A

perlecan & syndecan

194
Q

The plasma membrane of a cell has what kind of receptor that has high affinity for, for example, FGF

A

growth factor receptor

195
Q

What is an example of a transmember proteoglycan?

A

syndecan

196
Q

When a GAG presents a growth factor to receptor, the receptor has:

A

high affinity for it

197
Q

When a growth factor receptor binds a growth factor, what happens?

A

signal transduction pathway

198
Q

How can the ECM influence signal transduction?

A

Can present things for cell to bind to that start pathways, like growth factor

199
Q

What do entactin & perlecan bind to?

A

laminin & collagen IV

200
Q

Entactin & perlecan bind to laminin & colalgen IV in order to:

A

connect the 2 networks (pg 47)

201
Q

What ECM proteins does entactin bind?

A

perlecan & fibronectin

202
Q

How are GAGs an important part of the kidney glomerulus?

A

size-selection barrier & charge selective barrier

203
Q

How do GAGs act as a size-selection barrier in the kidney glomerulus?

A

HSPG prevent macromolecules from passing into urine from blood

204
Q

How do GAGs act as charge selective barrier in kidney glomerulus?

A

HSPGs give it negative charge, most proteins are neg. charged, so HSPGs repel them and don’t allow them to cross

205
Q

What happens to the kidney glomerulus in a person with diabetes?

A

the basal lamina becomes disorganized and doesn’t filtrate properly.

206
Q

Key words: hyperglycemia, HSPG defect, proteinuria, progressive renal failure, dialysis are what disease?

A

Diabetic Nephropathy: Hyperglycemia, Diabetes Mellitus

207
Q

Characteristics: Proteinuria, fluid retention, HTN → further damage → progressive renal failure; #1 indication for dialysis are what disease?

A

Diabetic nephropathy: hyperglycemia, diabetes mellitus

208
Q

What is the mechanism for diabetic nephropathy?

A

Hyperglycemia → downregulation of HSPG (perelcan), collagen glycosylation & crosslinking → GBM thickening: increased collagen, decreased HSPG → expansion of mesangial matric

209
Q

Where is the defect for diabetic nephropathy?

A

HSPG defect (basement membrane defect)

210
Q

Diabetic nephropathy will eventually lead to what?

A

Renal failure

211
Q

Describe the 6 main functions of the basal lamina

A

Structural support for cells (Transmembrane integrin receptors bind to collagen IV and Laminin)
Organises cells & tissues

Scaffold for tissue regeneration

Filter (kidney glomerlus; thick BL prevents macromolecules passing from blood to urine) (Collagen IV & HSPG important)

Determines cell polarity

Influences cell survival, proliferation, differentiation

Selective barrier for cell migration

212
Q

What will you not find in the basal lamina?

A

elastin & fibrillin

213
Q

What is fibronectin?

A

Adhesive glycoprotein that the cells integrin receptors bind to in interstitial matrix (like fibroblasts).

214
Q

Fibronectin ______ the ECM and helps ____ attach to it

A

organizes, cells

215
Q

Fibronectin connects cells to all ECM except for what?

A

Type IV ECM: Basal lamina mediated by laminin

216
Q

Fibronectin forms what?

A

dimers

217
Q

The fibronectin dimer is connected by what kind of bonds?

A

disulphide bonds

218
Q

Name the four binding domains of fibronectin

A

heparin binding
cell binding
collagen binding
self-association

219
Q

What aa sequence is within the cell binding domain?

A

RGD sequence

220
Q

The RGD sequence is found where?

A

on binding domain of fibronectin & laminin

221
Q

What do integrin receptors specficially bind to on fibronectin & laminin?

A

RGD aa sequence

222
Q

What is the function of the self association domain on the fibronectin?

A

when cells integrin receptors start binding to fibrnectins, the fibronectins will start associating toegether outsid ecell to form fibronectin fibrils

223
Q

RGD stands for what amino acids?

A

arginine, glycine, asparagine

224
Q

What binds to fibronectin?

A

collagen, proteoglycans, fibrin

225
Q

What secretes fibronectin?

A

fibroblasts

226
Q

fibrillar fibronectin mimics what in its formation?

A

the cytoskeleton of surrounding cells, and vice versa

227
Q

Describe the orientation of fibers in fibrillar fibronectin?

A

arranged in same orientation

228
Q

Fibronectin dimers _____ and assemble into fibrils by binding to integrins at cell surface

A

cross link

229
Q

Whose function is: Causes cells to assume their normal shapes & grow in the right direction (aligns cytoskeleton with fibronectin fibrils)

A

fibronectin

230
Q

What is a proteoglycan that helps with attachment b/w cell and ECM & helps w/ adhesion and signalling?

A

syndecan

231
Q

What functions as an alpha/beta heterodimer and is the main receptor for attaching cell to the ECM?

A

Integrins

232
Q

Is the bond b/w integrins and ECM strong?

A

No, each individual attachment is weak

233
Q

Each individual attachment to integrin and ECM is weak, explain how they are able to attach to ECM effectively

A

They function like velcro- individually they are weak but together they can form a strong enough bond. This helps for movement of cells, they can detach easily.

234
Q

What are the Principal cell receptors for binding ECM (collagen, fibrinogen, laminin)?

A

Integrins

235
Q

What links the ECM with intracellular signaling?

A

Integrins

236
Q

Name this anchoring junction: Integrins bind to actin stress fibers via adapter proteins, and to fibronectin

A

Focal adhesions

237
Q

Name this anchoring junction: Integrins bind to intermediate filaments (keratins) via adapter proteins, and to laminin

A

hemidesmosomes

238
Q

What binds to F-actin stress fibers in the cell?

A

adapter protein on integrin

239
Q

What binds to keratin in cell?

A

adapter protein on integrin

240
Q

What junction is very important during cell migration?

A

focal adhesions

241
Q

What is the “feet” of cell during cell migration

A

focal adhesions

242
Q

In focal adhesions, name the two adaptors for integrins and actin inside the cytoplasm of cell

A

vinculin & talin

243
Q

What is the protein that cross links alpha stress fibers (inside cell of a focal adhesion complex)

A

alpha actinin

244
Q

What kinase do integrins signal through to signal migration to cell?

A

FAK: focal adhesion kinase

245
Q

Growth factor can cause changes in what kind of receptor?

A

integrin. what integrin receptors bind to outside cell can cause changes inside the cell

246
Q

What is the strongest anchor b/w the cell and the ECM?

A

hemidesmosome

247
Q

What is the name of the intermediate filament important in hemidesmosomes?

A

keratin

248
Q

keratin inside cell are embedded into plaques containing:

A

plectin

249
Q

What does plectin bind to?

A

IFs

250
Q

What link the intracellular plaques to the ECM laminin in hemidesmosomes?

A

Integrin

251
Q

Hemidesmosomes are anchored by what kind of collagen?

A

VII

252
Q

key words: autoimmune, hemidesmosomes, blister formation ABOVE the basal lamina is what disease?

A

Bullous Pephigoid

253
Q

Characterstics: Subepidermal blisters or psoriasiform pattern; onset > 60 years are what disease?

A

bullous pephigoid

254
Q

What is the mechanism of bullous pephigoid?

A

Autoantibodies attacking hemidesmodomal protein (plectin plaques) → disrupts dermal-epidermal junction (rupturing between cell & basal lamina)

255
Q

Where is the defect in bullous pephigoid?

A

Autoimmune destruction of hemidesmosome [IF: cell-matrix]

256
Q

What disease has autoimmune destruction of hemidesmosomes?

A

bullous pemphigoid

257
Q

Draw out the attachements of focal adhesions & hemidesmosomes

A

Pg 67 & 69

258
Q

What 2 gene proteins are important for cell motility?

A

RAC & CDC42

259
Q

What is the function of Filopodia?

A

sensors to be sure cell is moving in right direction during migration

260
Q

What protein rearranges actin to stretch front out in a lamellopodium?

A

RAC

261
Q

What protein mediates new focal contacts made in cell migration?

A

RHO

262
Q

What G protein is important for stress fibers & focal contacts?

A

RHO

263
Q

What G protein is important for lamellipodium that extends from the entire circumference of the cell?

A

RAC

264
Q

What G protein is important for filopodia protrusion, form adhesive contacts with substratum ?

A

Cdc42

265
Q

What is the strongest form of cell -cell adhesion?

A

desmosomes

266
Q

Starting at the apical surface of the cell, name the order of appearance of cell-cell junctions

A
  1. tight
  2. adherins
  3. desmosomes
  4. gap
267
Q

What is another name for tight junction?

A

Occluding Junction or Zonula occludens

268
Q

What is a barrier that completely encircles the apical layer of each cell?

A

Tight junction

269
Q

What transmembrane adhesion proteins help form the tight junction?

A

claudin & occludin

270
Q

What kind of junction determines epithelial cell polarity?

A

Tight junction

271
Q

What do they think is downregulated in inflammatory bowel disease that allows for more permeability of membrane for WBC to cause immune response?

A

occludin

272
Q

Anchoring receptors and desmosomes use what family of proteins ?

A

cadherins

273
Q

Cadherins are dependent on what ion?

A

calcium

274
Q

What forms continuous adhesion belt (zonula adherens) in epithelia just below TJs

A

Adherens junctions

275
Q

In adheren junction, the E cadherin of one cell binds to what part of adj. cell?

A

E. cadherin

276
Q

How do cadherins bind to the actin cytoskeleton?

A

via catenins

277
Q

If actin are cross linked by alph actinin, will they be contractile?

A

Yes, they are loosely packed so will be contractile

278
Q

What is the difference b/w adherens junctions & desmosomes?

A

Major difference between desomosomes & adherens (belt) junctions:
Adherens junctions connect to F-actin, not IFs
Adherens junctions are near the apical surface (actin-rich region)
Form a continuous belt around cell, not spot welds
Linker proteins = catenins (important signaling molecules; GI & hepatic cancer)

279
Q

What are the two specific intracellular anchor proteins that attach to cadherins in desmosomes?

A

desmoplakin & plakoglobin

280
Q

What do desmoplakin & plakoglobin bind to?

A

IFs & cadherin

281
Q

Desmoplakin & plakoglobin are both part of what that binds to IFs and are connected via cadherins?

A

plaques

282
Q

key words: autoimmune, desmosomes, blistering are what disease?

A

Pemphigus vulgaris

283
Q

Characteristics:Blistering & raw sores on skin & mucous membrane are what disease?

A

Pemphigus vulgaris

284
Q

What is the mechanism for pemphigus vulgaris?

A

Antibodies attacking desmosomal proteins → skin pulls apart → abnormal movement of fluid within skin → blisters

285
Q

What is the mode of inheritance for pemphigus vulgaris?

A

autoimmune disorder

286
Q

Where is the defect in pemphigus vulgaris?

A

Autoimmune destruction of desmosomal cadherins(anti-desmogelin) [IF: cell-cell]

287
Q

What connects both cytoplasms in a gap junction?

A

connexons

288
Q

What forms a connexon?

A

6 connexin subunits

289
Q

What cell connection allows free passage of ions, sugars, aas, nucleotides, 2nd messengers (cAMP, IP3)?

A

gap junctions

290
Q

What are the two main functions of gap junctions?

A

electrical coupling & chemical coupling

291
Q

The coordinated depolarisation of the heart is an example of what function of gap junctions?

A

electrical coupling

292
Q

2nd messengers, like in cAMP pathway, is an example of what function of gap junctions?

A

chemical coupling

293
Q

What does CMT stand for?

A

Charcot-Marie-Tooth

294
Q

Briefly describe Charcot-Marie-Tooth

A

Name: Charcot-Marie-Tooth Neuropathy Defect: Connexin Mutation [cell-cell gap junction] Mode of Inheritance: X-linked Mechanism: Mutation of connexin 32 ! demyelination of Schwann cells ! progressive degeneration of peripheral nerve function Characteristics: Muscle weakness & atrophy, impairment of deep tendon reflexes Key words: connexin, gap junction, deep tendon reflexes

295
Q

Selectins belong to what class of proteins?

A

lectins

296
Q

What are selectins?

A

proteins that bind to sugar chain instead of actual protein

297
Q

What type of selectin is expressed on WBC?

A

L-selectin (L = leukocyte)

298
Q

What type of selectin is expressed on platelets?

A

P-selectin

299
Q

What type of selectin is expressed on endothelial cells?

A

E-selectin

300
Q

Draw out all the steps in lymphocyte rolling, and explain each part

A

See slide 124 in ECM & cell interactions

301
Q

What is diapedesis?

A

WBC migration into tissue

302
Q

What is the weak adhesion and what is the strong adhesion in lymphocyte rolling?

A

weak: selectins on endothelial cells

strong; Integrin binds ICAM on endothelial cells

303
Q

What happens if there is a mutation in beta2 integrin?

A

Inherited mutation in beta 2 integrin. Integrin are heterodimres beta 2 is one of the integrins that’s really important in leukocyte extravasation. Mutation in integrin, when there is infection will get activation of nearby endothelial cells which express selectins, leukocytes bind, but cant get tracking .if cell cant be tracked b/c integrin cant bind to ICAMS it will just keep rolling along.
ultiamtely the pt will suffer from lots of bacterial infections

304
Q

key words: B3 integrin, glycoprotein IIb-IIa, platelet aggregation defect is what disease?

A

Glanzmann’s Thrombasthenia

305
Q

Characteristics: Excess bruising and bleeding is what disease?

A

Glanzmann’s Thrombasthenia

306
Q

What is the mechanism of Glanzmann’s Thrombasthenia ?

A

Absence of platelet integrin complex → no binding to fibrinogen → failure of platelet aggregation → defective clotting

307
Q

Where is the defect in glanzmann’s thrombasthenia?

A

Mutation of B3 integrin (glycoprotein IIb-IIIa)

308
Q

List the collagen defect disorders

A 
Osteogenesis Imperfecta		Collagen I
Ehlers-Danlos syndrome		Collagen I, III, V
Alport syndrome			Collagen IV
Goodpasture syndrome		Collagen IV
Epidermolysis bullosa		Collagen VII

MCB1 Block 3 (15 decks)

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