Ec Matrix I And Ii

Front 1

extracellular matrix: defn

Back 1

Intricate network of macromolecules, separate from cells, that make up tissues.

In connective tissue, the EM is much more plentiful than cells. Forms architectural framework of the vertebrate body.

Front 2

What is the extracellular matrix primarily composed of? (3)

Back 2

Collagen
Elastin
Proteoglycans

Front 3

Collagens: defn

Back 3

Family of fibrous proteins with a characteristic triple-stranded helical structure.

Extremely strong. About 25% of all protein in the body is collagen.

Front 4

What is the structure of a collagen strand?

Back 4

>1400 a.a. long

Made of repeated sequence of <b> glycine, proline, and hydroxyproline. </b>

Front 5

What cells produce collagen?

Back 5

Fibroblast (progenitor)

Bone cells (osteoblast/osteocyte)
Cartilage cells (chondrocytes)
Smooth Muscle cells

Front 6

What four types of cells can fibroblasts differentiate into?

Back 6

Bone cells (osteoblast/osteocyte)
Smooth muscle cells
Cartilage cells

(All these can make collagen)

Also differentiates into fat cells (adipocyte) which does NOT make collagen.

Front 7

Type I Collagen

Back 7

Simplest type of collagen

Long stretch of triple helix with blunt ends. Associate side-by-side, like rope fibers to form tough fibrils.

Found in dermis, bone, cornea, tendon, fibrocartilage, vessels, intestine, dentin, skin, uterus

<b> 80% of collagen in skin. </b>

Front 8

Basement membrane

Back 8

thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels. Forms a tough surface that supports the skin and many organs.

Composed of <b> Type IV Collagen</b> that has a globular head at one end and an extra tailo n the other. The heads bind strongly together, and four collagen molecules associate together through their tails, forming an X-shaped complex.

Front 9

Type IV Collagen

Back 9

forms bases of cell basement membrane.

Has a globular head at one end and an extra tail at the other. The heads bind strongly together and four collagen molecules associate together thru their tails, forming X shaped complex.

Type IV Collagen forms an extended network.

Front 10

What happens to basement membrane function in diabetes?

Back 10

Glucose non-selectively binds throughout basement membrane and blocks ability to filter. Especially important in kidney glomerulus.

Front 11

Osteoblasts vs. Osteoclasts

Back 11

Blasts build bone, clasts erode it.

Front 12

osteocytes

Back 12

mature osteoblasts that are imprisoned in bone matrix. They no longer divide but continue to secrete matrix in small quantities.

they occupy lacuna (small cavities) and canaliculli (small channels) radiate from each lacuna.

Front 13

How are osteocytes connected?

Back 13

Through the canaliculli (small channels), cell processes connect the osteocytes via gap junctions.

Front 14

Osteoclasts

Back 14

Large, multinucleated cells that originate from hemopoietic stem cells in bone marrow.

they can tunnel deep into bone and form cavities that are invaded by other cells. A capillary can then grow down the center and the walls become lined with osteoblast layer.

Front 15

Post-translational processing of collagen

Back 15

1) Formation of hydroxyproline
2) Formation of hydroxylysine
3) Adding of Galactose
4) Adding of Glucose
5) Removal of N and C terminal domains
6) Cross-link and fiber formation
7) Degradation and remodeling

Front 16

What cofactors does the formation of hydroxyproline and hydroxylysine require?

Back 16

Vitamin C
Iron
Oxygen
alpha keto glutarate

Front 17

What's special about teh collagen gene?

Back 17

Has more introns/exons than any other protein, requiring extensive processing prior to translation.

Front 18

Hydroxylsine formation

Back 18

Requires enzyme lysyl hydroxylase to add hydroxyl group to lysine. uses same cofactors and molecular oxygen.

Front 19

What does Vitamin C deficiency do?

Back 19

Inhibits the hydroxylation of proline and stops synthesis of new collagen.

Symptoms of scurvy (bleeding, loss of teeth) are caused by lack of collagen to repair daily wear and tear.

Front 20

Glycosylation of collagen

Back 20

Selected hydroxylysine residues get galactose and glucose added to them. Catalyzed by galactosyl and glucosyl transferase.

Diabetics can have too much sugar added to their collagen and filtration function of basal lamina is lost.

Front 21

non-enzymatic glycosylation

Back 21

process by which too much glucose is added to collagen in diabetics, interfering with function, especially in kidney glomerulus.

Front 22

movement of collagen within the cell and secretion to extracellular spaces

Back 22

Gets cross links between chains and among chains

Extension peptides that are non-helical are added

Front 23

Galactosyl and Glucosyl Transferase

Back 23

Enzymes that add glucose or galactose to selected hydroxylysine residues. Very tightly controlled process, gets out of control in diabetics.

Front 24

Procollagen processing and relationship to the control of collagen synthesis

Back 24

When both the C and N terminal extension peptides are present, the molecule is 1000x more soluble than after they're cleaved. After they're removated, the peptides are digested and taken up by the cell to regulate collagen synthesis in a feedback mechanism.

Removal of the N and C terminal domains is another post-translation modification.

Front 25

Registration of collagen

Back 25

Alignment of the 3 alpha chains. Disulfide bonds in the C-terminal extension peptides form to ensure this.

Front 26

Cross link and fiber formation of collagen

Back 26

Another impt post-translation modification; critical for proper wound healing.

Inter- and intra-molecular cross links formed by action of lysyl oxidase on selected lysine and hydroxylysine residues using copper as cofactor

Front 27

lysyl oxidase

Back 27

enzyme that forms crosslinks in collagen on selected lysine and hydroxylysine residues using copper as a cofactor.

Front 28

Wilson's disease

Back 28

Liver doesn't excrete excess copper into the bile as it normally does, as a result, copper accumulates in and damages the liver. As a result, copper leaves the liver and goes to the bloodstream and accumulates in brain and eyes.

Front 29

Collagen degradation and remodeling

Back 29

Final post translational modification

Controlled by collagenases (type of Matrix Metallo Proteinase)

Front 30

Formation of collagenase

Back 30

Procollagenase (a zymogen) is made. Then is converted to active enzyme by either plasmin cleavage, low pH, or reactive oxygen species.

Front 31

What converts plasminogen to plasmin?

Back 31

TPA
Tissue Plasminogen Activator

Also known as a clot buster, used in ischemic strokes.

then plasmin breaks down the clot (mainly by breaking down fibrin)

Front 32

What does plasmin do (wrt collagen)?

Back 32

Converts procollagenase to collagenase

Front 33

How can you inhibit collagenase?

Back 33

Alpha-2-macroglobulin (physically binds to enzyme and blocks activity)

Alpha-1-Antitrypsin.

Tissue Inhibitor of Metallo Proteinase (TIMP)

Front 34

How do collagenases play a role in tumor metastasis?

Back 34

Primary tumors (e.g., breast tumors) can have extra matrix metallo proteinases that can come out of blood vessels and break thru into another site.

Front 35

Ehlers-Danlos Syndrome

Back 35

Grouped together as a class.

Patients have very stretchable skin.

Collagen is not properly put together and is loose.

Front 36

Osteogenesis imperfecta

Back 36

defective connective tissue, or without the ability to make it, usually because of a deficiency of Type-I collagen

Group of connective tissue defects have frequent bone fractures

Front 37

Elastin

Back 37

Another major component of the ECM.

Biochem props allow for maximal stretch and recoil.

Highly hydrophobic.

1/3 of amino acids are glycine, but gly is distributed RANDOMLY thru Elastin (evenly through Collagen).

Crosslinked by covalent bonds that link 4 elastins into either desmosine or isodesmosine.

Front 38

desmosine and isodesmosine

Back 38

Unique to elastin, they're cross links that pull elastin together.

Their formation requires lysyl oxidase (also involved in collagen crosslinking).

Front 39

Where is elastin found?

Back 39

Yellow connective tissue in walls of large vessels, lungs, skins, some in ligaments and cartilage.


NOT in scar tissue.

Front 40

How is elastin made?

Back 40

Gene is one of the largest in the genome.

Synthesized on membrane-bound polysomes and secreted into the extracellular space where forms an extensive network held together by desmosine or isodesmosine (specialized cross links).

Front 41

Fibrillin

Back 41

A negatively charged microfibrillar glycoprotein that interacts with elastin.

Front 42

What is the difference between glycoproteins and proteoglycans?

Back 42

Glycoproteins: 90% protein, 10% carbohydrate

Proteoglycans: 10% protein, 90% carbohydrate

Front 43

Glycosaminoglycans

Back 43

Very long unbranched chains of disaccharide amino sugars.

Groups of them are linked to a "core protein" which is linked via a "link protein" to a backbone of hyaluronic acid to form proteoglycans.

Front 44

Proteoglycan: defn

Back 44

Specialized components of ECM made of glycosaminoglycan building blocks.

Front 45

How are proteoglycans made?

Back 45

The core protein is made on membrane bound ribosomes. As it is passed thru the golgi, glycosaminoglycans are added by specific membrane bound transferases.

Front 46

hyaluronic acid

Back 46

nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. <b>It is unique among glycosaminoglycans in that it is nonsulfated, forms in the plasma membrane instead of the Golgi, and can be very large, with its molecular weight often reaching the millions. Also it does not attach to protein.</b>

Front 47

6 Classes of Glycosaminoglycans

Back 47

Hyaluronic acid

Chondroitin Sulfate

Heparin Sulfate

Heparin

Dermatan Sulfate

Keratin Sulfate

Front 48

What's the structure of proteoglycans?

Back 48

Backbone of hyaluronic acid.

Link proteins come off it and attach to core proteins. GAGs come off the core proteins.

Looks like a bottle brush.


These molecules sequester a lot of fluid and function as a cushion.

Front 49

Hunter and Hurler syndrome

Back 49

Defects in degradation of GAGs (problem with lysosomal enzyme).

Causes mental retardation and skeletal abnormalities.

Front 50

Primary function of proteoglycans

Back 50

Function as lubricants in synovial fluid, shock absorbers in spinal column, and reservoirs for nutrients etc. Hyaluronic acid is also very important for cell migration in embryonic development and wound healing.

Front 51

Fibronectin

Back 51

Large glycoprotein made of two peptides held together by disulfide bonds and <b>binds</b> cells via tripeptide sequence (Arg-gly-asp, R-G-D) to collagen, proteoglycans, and other components of the ECM.

It is involved in cell adhesion, growth, migration and differentiation. Cellular fibronectin is assembled into the extracellular matrix, an insoluble network that separates and supports the organs and tissues of an organism.

Fibronectin plays a crucial role in wound healing.[6] Along with fibrin, plasma fibronectin is deposited at the site of injury, forming a blood clot that stops bleeding and protects the underlying tissue.

Front 52

Laminin

Back 52

Large glycoprotein that binds type IV collagen, heparin sulfate, and cells.

A component of the <b>basal lamina.</b>

Front 53

Integrin

Back 53

receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM).

Group of plasma membrane glycoproteins that bind cell to specific binding domains of ECM. Many recognize the Arg-gly-asp/R-G-D sequences of matrix components.

Front 54

Basal lamina: purpose and what is it made of?

Back 54

Complex structure whose main purpose is filtration.

Made of Type IV Collagen, Laminin, and Proteoglycans.

Front 55

Collagen: structure and function

Back 55

Structure: Triple helical glycoprotein, with proline, hydroxyproline, and glycine repeating.

Function: Strength, support and structure for all tissues and organs.

Front 56

Elastin: structure and function

Back 56

Structure: Stretchable hydrophobic protein interacting with glycosylated microfibrils.

Function: Allows tissues and other structures to expand and contract. Not found in scar tissue.

Front 57

Fibronectin: structure and function

Back 57

Structure: Specialized adhesive glycoprotein.

Function: Mediates cell-ECM adhesion.

Front 58

Laminin: structure and function

Back 58

Structure: Large complex adhesive glycoprotein

Function: Binds cells to type IV collagen and heparin sulfate in basal lamina.

Front 59

Proteoglycans: structure and function

Back 59

Structure: Heterogenous, long glycosaminoglycan chains covalently linked to a core protein

Function: Moisture stores, shock absorption, sequestration of cytokines.

Front 60

Hyaluronic acid: structure and function

Back 60

Structure: Very large, specialized, non-sulfated GAG.

Function: Provides fluid envt for cell movement and differentiation. Also binds to cytokines. Forms backbone of proteoglycan.