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pH - Foundations 08-10-17 > ECM > Flashcards

ECM Flashcards

1
Q

GAGs

A

Glycosaminoglycans

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2
Q

Hyaluronan

A

GAG w/ no SO3

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3
Q

Keratan Sulfate

A

GAG w/ no acidic sugar

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4
Q

Core Protein w/ Hyaluronan

A

Aggrecan

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5
Q

GAGs Plus Core Protein

A

Proteoglycans

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6
Q

Why Are Proteoglycans Smaller Than GAGs?

A

They are bound to membrane

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7
Q

Name 3 Proteoglycans

A
  1. Syndecan (spanning)
  2. Glypican (GPI anchor)
  3. Perlecan (secreted)
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8
Q

What Are the Most Abundant GAGs in the body? What do they make up?

A
  1. Chondroitin 4 - Sulfate
  2. Chondroitin 6 - Sulfate

Cartilage (bind collagen), tendons, ligaments, aorta

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9
Q

What GAG is in the skin, blood vessels, and heart valves?

A

Dermatan Sulfate

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10
Q

What is the most diverse GAG?

A

Keratin Sulfate (KS)

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11
Q

KS 1

A

Corneas

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12
Q

KS 2

A

Loose connective tissue with chondroitin sulfate

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13
Q

KS 3

A

Brain

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14
Q

Is Hyaluronate covalently bound to proteins? Where is it found? Involved in?

A

No
Bacteria, synovial fluid (lubricant) and shock absorber
Metastasis

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15
Q

Heparin (GAG)

A

Intracellular in mast cells (WBC) lining arteries (liver, lungs, skin) and is an anticoagulant

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16
Q

Heparin Sulfate (GAG)

A

Has acetylation (less sulfates). Extracellular GAG (basement membrane)

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17
Q

What does Heparin bond to?

A

Antithrombin 3

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18
Q

What are the 2 mucopolysaccharidose lysozyme storage diseases?

A
  1. Hurler’s Syndrome (developmental delays, gargoylism, airway obstruction, clouded cornea, hearing loss)
  2. Hunter’s Syndrome (mild Hurler + aggression)

Can’t break down GAG’s and can be delayed

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19
Q

What accumulates in Hurler’s/Hunters?

A

Heparan Sulfate and Dermatan Sulfate

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20
Q

What enzyme is affected in Hunter’s? What is the issue?

A

Iduronate Sulfatase. Cannot take off Sulfur (enzyme replacement theory)

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21
Q

What enzyme is affected in Hurler’s? What’s the issue?

A

Alpha-L-iduronidase. Cannot take off sugar

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22
Q

Sly Syndrome

A

No sugar off

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23
Q

How can Hurler’s be treated?

A

Bone marrow or cord blood transplantation

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24
Q

What do you make collagen with?

A

a) 2 alpha 1’s

b) 1 alpha 2

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25
Q

2 Patters in Collagen Helix

A
  1. Gly-Pro-X

2. Gly-X-Hydroxyproline

26
Q

Scurvy is what type of collagen impairment?

A

Fibril

27
Q

Symptoms of scurvy?

A

Lethargy & malaise, bruises due to capillary fragility, gum disease, poor wound healing

28
Q

Is Ehler’s lethal? Most common a.a. mutations?

A

No; type 3 is most clinically significant (vascular) and type 5 is classical (joint and skin) also class 1

29
Q

What type of collagen is affected in osteogenesis imperfecta and is it autosomal what?

A

Collagen type 1; autosomal dominant

30
Q

What are 4 cell adhesion molecule families?

A
  1. Selectins
  2. Immunoglobulin Superfamily
  3. Integrins
  4. Cadherins
31
Q

What ligand does selectins recognize? Is it a stable cell junction?

A

Carbs; no

32
Q

What ligand does IG superfamily recognize? Stable cell junction?

A

IgSF members, integrins; not usually for either

33
Q

What ligand does integrins recognzie? Stable?

A

EC matrix - focal adhesions

IG superfamily, Cadherins - hemidesmosomes

34
Q

What ligand does cadherins recognize? Stable?

A

Other cadherins - adherens junctions, desmosomes

35
Q

Which family does not require Ca+2, Mn+2, or Mg+2?

A

Ig

36
Q

What motiff do integrins recognzie?

A

RGD (arginine, glycine, aspartic acid) any compound that has thing, integrins will bind

37
Q

How many units in integrins? This relates to what?

A

24; metastasis

38
Q

Where do integrins function?

A

Focal adhesions, hemidesmosomes

39
Q

What is inside focal adhesions? Hemidesmosomes?

A

Actin filaments (talin, ECM); intermediate filaments basal lamina)

40
Q

What does talin do? What else is involved?

A

Binds to integrin to activate it; kindlin

41
Q

MMP

A

Matrixmetalloprotease; eats away at ECM to help cancer metastasize

42
Q

What binds and activates MMP-2?

A

Alpha 5 beta 3 integrin

43
Q

What 3 things do Adherins use?

A
  1. Actin filaments inside; across cell using 1 protein each side
  2. Beta Catenin
  3. Alpha Catenin (the catenins help bind actin filament)
44
Q

Desmosome uses what?

A

Intermediate filaments

45
Q

2 places for tight junctions. Is it strong?

A
  1. Epithelium
  2. BBB

No; just separate 2 things in the body

46
Q

What 3 things in tight interacts with actin? What do they bind?

A
  1. JAM
  2. Occludin
  3. Claudin

PDZ

JOC (K)

47
Q

Gap Junctions

A

Extension of the cell

48
Q

Gap Junction Disease. Symtpoms?

A

Charcot-Marie-Tooth (CMT)

Degeneration of nerves, slow loss of muscle control, cataracts, deafness

49
Q

What is fibronectin?

A

Matrix adhesions; crosslinks with GAGs and combines with integrins

50
Q

What are the 2 types of fibronectins?

A
  1. Insoluble (forming ECM as fibrils)

2. Soluble (blood - clotting)

51
Q

What is Fibrosis?

A

Increased deposition of EC matrix proteins into tissues (scar, organ failure)

52
Q

Fibrosis (45% of deaths in 2008) Blood Clotting

A

Fibronectin and fibrin cross link until collagen deposited (this is good)

53
Q

Fibrosis =

A

Bad. Macrophages increase TGB beta, fibroblasts increase in matrix output - scarring

54
Q

MMP’s digest what? Involved in what?

A

Collagens, laminins; movement of cells, development/growth, tissue repair

55
Q

When do MMP’s increase?

A

Cancer

56
Q

2 things that change in all cancers

A

Integrins and MMPs

57
Q

Elastin mainly what?

A

Small, non-polar (rich in pro and gly)

58
Q

Why not super rigid like collagen?

A

Crosslinks not a lot and can pull the crosslinks apart

59
Q

What does smoking mess up for inhibition of elastase?

A

Methione in antitrypsin to bind elstase

60
Q

What is fibrillin?

A

Glycoprotein scaffold for elastin

61
Q

Marfan

A

Impaired structural activity

pH - Foundations 08-10-17 (4 decks)

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