Flashcards in ECM Deck (61):
GAG w/ no SO3
GAG w/ no acidic sugar
Core Protein w/ Hyaluronan
GAGs Plus Core Protein
Why Are Proteoglycans Smaller Than GAGs?
They are bound to membrane
Name 3 Proteoglycans
1. Syndecan (spanning)
2. Glypican (GPI anchor)
3. Perlecan (secreted)
What Are the Most Abundant GAGs in the body? What do they make up?
1. Chondroitin 4 - Sulfate
2. Chondroitin 6 - Sulfate
Cartilage (bind collagen), tendons, ligaments, aorta
What GAG is in the skin, blood vessels, and heart valves?
What is the most diverse GAG?
Keratin Sulfate (KS)
Loose connective tissue with chondroitin sulfate
Is Hyaluronate covalently bound to proteins? Where is it found? Involved in?
Bacteria, synovial fluid (lubricant) and shock absorber
Intracellular in mast cells (WBC) lining arteries (liver, lungs, skin) and is an anticoagulant
Heparin Sulfate (GAG)
Has acetylation (less sulfates). Extracellular GAG (basement membrane)
What does Heparin bond to?
What are the 2 mucopolysaccharidose lysozyme storage diseases?
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
What accumulates in Hurler's/Hunters?
Heparan Sulfate and Dermatan Sulfate
What enzyme is affected in Hunter's? What is the issue?
Iduronate Sulfatase. Cannot take off Sulfur (enzyme replacement theory)
What enzyme is affected in Hurler's? What's the issue?
Alpha-L-iduronidase. Cannot take off sugar
No sugar off
How can Hurler's be treated?
Bone marrow or cord blood transplantation
What do you make collagen with?
a) 2 alpha 1's
b) 1 alpha 2
2 Patters in Collagen Helix
Scurvy is what type of collagen impairment?
Symptoms of scurvy?
Lethargy & malaise, bruises due to capillary fragility, gum disease, poor wound healing
Is Ehler's lethal? Most common a.a. mutations?
No; type 3 is most clinically significant (vascular) and type 5 is classical (joint and skin) also class 1
What type of collagen is affected in osteogenesis imperfecta and is it autosomal what?
Collagen type 1; autosomal dominant
What are 4 cell adhesion molecule families?
2. Immunoglobulin Superfamily
What ligand does selectins recognize? Is it a stable cell junction?
What ligand does IG superfamily recognize? Stable cell junction?
IgSF members, integrins; not usually for either
What ligand does integrins recognzie? Stable?
EC matrix - focal adhesions
IG superfamily, Cadherins - hemidesmosomes
What ligand does cadherins recognize? Stable?
Other cadherins - adherens junctions, desmosomes
Which family does not require Ca+2, Mn+2, or Mg+2?
What motiff do integrins recognzie?
RGD (arginine, glycine, aspartic acid) any compound that has thing, integrins will bind
How many units in integrins? This relates to what?
Where do integrins function?
Focal adhesions, hemidesmosomes
What is inside focal adhesions? Hemidesmosomes?
Actin filaments (talin, ECM); intermediate filaments basal lamina)
What does talin do? What else is involved?
Binds to integrin to activate it; kindlin
Matrixmetalloprotease; eats away at ECM to help cancer metastasize
What binds and activates MMP-2?
Alpha 5 beta 3 integrin
What 3 things do Adherins use?
1. Actin filaments inside; across cell using 1 protein each side
2. Beta Catenin
3. Alpha Catenin (the catenins help bind actin filament)
Desmosome uses what?
2 places for tight junctions. Is it strong?
No; just separate 2 things in the body
What 3 things in tight interacts with actin? What do they bind?
Extension of the cell
Gap Junction Disease. Symtpoms?
Degeneration of nerves, slow loss of muscle control, cataracts, deafness
What is fibronectin?
Matrix adhesions; crosslinks with GAGs and combines with integrins
What are the 2 types of fibronectins?
1. Insoluble (forming ECM as fibrils)
2. Soluble (blood - clotting)
What is Fibrosis?
Increased deposition of EC matrix proteins into tissues (scar, organ failure)
Fibrosis (45% of deaths in 2008) Blood Clotting
Fibronectin and fibrin cross link until collagen deposited (this is good)
Bad. Macrophages increase TGB beta, fibroblasts increase in matrix output - scarring
MMP's digest what? Involved in what?
Collagens, laminins; movement of cells, development/growth, tissue repair
When do MMP's increase?
2 things that change in all cancers
Integrins and MMPs
Elastin mainly what?
Small, non-polar (rich in pro and gly)
Why not super rigid like collagen?
Crosslinks not a lot and can pull the crosslinks apart
What does smoking mess up for inhibition of elastase?
Methione in antitrypsin to bind elstase
What is fibrillin?
Glycoprotein scaffold for elastin