Basic Science - Extracellular Matrix

Front 1

The extracellular matrix is the _____ in connective tissues between cells

Back 1

ground substance

Front 2

The main components of extracellular matrix are:
What do they do?

Back 2

-collagen - provides tensile strength
-elastic fibers - provides resilience
-proteoglycans - provides resilience
-hyaluronan - provides resilience
-glycoproteins - mediate adhesive interactions between other matrix molecules or between cells and matrix molecules

Front 3

Collagen is the main _____ in connective tissue. It has a characteristic _____. It is heavily _____ and very ______

Back 3

-fibrillar proteins
-triple helical structure
-linked
-stable

Front 4

What are the fibril forming collagen types? And where are they distributed

Back 4

-Type I - skin, bone, tendon, blood vessels, cornea

-Type II - cartilage, intervertebral disk, vitreous body (fluid in eye)

-Type III - blood vessels, fetal skin

Front 5

What are the network forming (forms meshes) collagen types? And where are they distributed

Back 5

-Type IV - basement membrane

Front 6

What is the precursor to collagen?

Back 6

procollagen

Front 7

Procollagen peptide chain has propeptides that are ______ after three procollagen chains assemble to form a ______

Back 7

-removed extracellularly by proteolytic digestion

-triple helical structure

Front 8

Collagen are composed of _____

Back 8

3 alpha chains (can be identical or different)

Front 9

Name what types of alpha chains Type I - Type 4 collagen are composed of:

Back 9

Front 10

The long helical part of alpha chains of collagen are composed of _____ repeats. These repeats favor ____

Back 10

Gly - X - Y
-X - proline
-Y - hydroxyproline

Triple helix formation

Front 11

Synthesis of the procollagen genes occur in the _____

Back 11

RER

Front 12

On procollagen, certain proline and and lysine residues are hydroxylated into _______. Then, certain _____ are _____

Back 12

-hydroxyproline and hydroxylysine
-hydroxylysine
-glycosylated

Front 13

When are prolines and lysines hydroxylated during the synthesis of collagen?

Back 13

During synthesis of alpha chains in the RER

Front 14

Triple helix formation of collagen forms in the ______

Back 14

RER

Front 15

Triple helix formation of collagen formation proceeds from the _____ end to the ____ end

Back 15

C-terminal end to the N-terminal end

Front 16

Triple helix formation of collagen is held together by ______. _____ also has a crucial role in stable triple helix formation

Back 16

-hydrogen bonds
-hydroxylproline

Front 17

After the triple helix formation is made, the procollagen is sent to the ______ where ______ are cleaved by ______. Once they are cleaved, collagen monomers assemble into ____

Back 17

-extracellular matrix
-N-terminal and C-terminal peptides
-N and C procollagen peptidases
-fibrils

Front 18

Collagen fibrils, which are formed by _____ associate in a _____ manner. These are stabilized ______ and it creates a ______ patterns when viewed under an electron microscope

Back 18

-collagen monomers
-staggered
-by covalent crosslinking between monomers
-striated

Front 19

Triple helix of collagen is stabilized by ______. Hydroxyproline produced by ______ which requires _____ as cofactors

Back 19

-Hydrogen bonds and hydroxyproline
-prolyl hydroxylase
-Fe2+ and vitamin C (ascorbate)

Front 20

Covalent crosslinks within collagen fibers are created through formation of _______. Oxidation of these two is catalyzed by ______, which requires ____ as a cofactor

Back 20

-oxidized lysine and hydroxylysine residues
-lysyl oxidase
-Cu2+

Front 21

Oxidation of lysine and hydroxylysine residues creates _______which react with _______ residues to create _______ between collagen

Back 21

-allysine or hydroxyallysine
-lysine/hydroxylysine/allysine/hydroxyallysine
-covalent crosslinks

Front 22

Collage IV is the main ______. Collagen IV alpha chains form triple helix ____

Back 22

-basement membrane
-inside the cell

Front 23

Type IV monomers attach at their C-terminal to form a _____ in the _____. The dimers N terminals then attach to form _____ and eventually a large networking looking like ____

Back 23

-dimer
-extracellular space
-tetramer
-chicken-wire

Front 24

What deficiency and disease is caused by the lack of fruits and vegetable in a diet?
This causes what enzymes to not work?
This causes what kind of symptoms?

Back 24

-Scurvy and Vitamin C disease
-Prolyl hyroxylases (stabilizes triple helix formation) and lysyl hydroxylase (crosslinks collagen)
-spots, bruises on skin (especially on leg); bleeding gums/loose teeth, delayed wound healing

Front 25

What are the three types of Ehlers-Danlos syndrome (EDS) and what types of mutations do they cause?

Back 25

Classic Type: type V collagen mutation (fibril associated collagen)

Vascular Type: type III collagen mutation

Kyphoscoliotic Type: lysyl hydroxylase mutation

Front 26

Classic type EDS is caused a mutation in what and causes what kind of symptoms?

Back 26

Type V collagen mutation
Symptoms: hypersensitive skin, delayed wound healing, atrophic scars, joint hypermobility

Front 27

Vascular type EDS is caused by a mutation in what and causes what kind of symptoms?

Back 27

Type III mutation
Symptoms: arterial, intestinal, and uterine (during pregnancy) ruptures

Front 28

Kyphoscoliotic type EDS is caused by a mutation in what and causes what kind of symptoms?

Back 28

lysyl hydroxylase mutation
Symptoms: hypersensitive skin, delayed wound healing, easy bruising, thin scars; joint hypermobility; progressive scoliosis

Front 29

Osteogenesis imperfecta has has at least _____ different types
Types I, II, III, IV are associated with what type of mutation?

Back 29

-seven
-Type I collagen mutation

Front 30

What are they symptoms of osteogenesis imperfecta?

Back 30

-can range from perinatal lethal to mild predisposition to fractures including:

-increased incidence of fractures
-short stature
-grey/brown teeth that wear down easily (dentinogenesis imperfecta)
-blue sclera
-loose ligaments

Front 31

Alport syndrome is a mutation of ______ genes and is related to ____

Back 31

-type IV collagen
-neuropathy

Front 32

Alports syndrome mainly effects ______ and can lead to ____ failure. The main symptoms of this disease are:

Back 32

-glomerular basement membranes
-renal failure
Symptoms:
-Hematuria
-Proteinuria
-Hepertension
-Renal insufficiency
-Hearing loss

Front 33

_____ is the major component of elastic fibers. It is mainly found in the _______. It is synthesized in the ____

Back 33

-elastin
-blood vessels and lungs
-ER

Front 34

Elastin is secreted from the cell as what?
When it is secreted, what happens?

Back 34

-monomers
-lysine residues are oxidized by lysyl oxidase, then they form crosslinks between elastin molecules

Front 35

The correct assembly of elastic fibers require what?
And what forms these?

Back 35

-microfibrils formed by fibrillins

Front 36

What is responsible for excessive degradation of elastin in the lungs?
How does it stop excessive degradation of elastin?

Back 36

-alpha1 - antitrypsin is a natural inhibitor of neutophil elastase (a proteolytic enzyme)
-neurtophil elastase degrades elastin in the lungs

Front 37

What does deficiency in alpha 1-antitrypsin leads to what?
Who may have an increase in this deficiency?

Back 37

-lower elastin content in lungs, can lead to collapse of alveoli when patient exhales, and leads to emphysema (shortness of breath)

-smokers are prone to deficiency

Front 38

Marfan syndrome is caused by deficiency in what?

Back 38

fibrillin-1 (microfibrils are deficient, which leads to a deficiency in elastic fibers)

Front 39

Marfan syndrome can occur in three places, where and what are its symptoms in those locations?

Back 39

Skeletal
-very tall stature, kyphoscoliosis
-disproportionally long limbs, finger and toes
-hyperflexible joints

Ocular:
-dislocation of lens of eyes (ectopia lentis)

Cardiovascular
-dilation of aorta
-heart valve problems

Front 40

Cells have dynamic interactions with the extracellular matrix. Resident cells ____ the extracellular matrix, while the extracellular matrix provides _____ for the cells. Cells bind to matrix through_____, which allow cells to sense ____ in the extracellular matrix and respond

Back 40

-synthesize
-optimal environment
-cell surface receptors
-changes
(ex. if tissue is damages, primary response is to restore integrity of tissue by resynthesizing tissue)

Front 41

What are the main receptors that anchor the cells to the extracellular matrix?
These can bind to what?

Back 41

-integrins (alpha-beta dimer)
-collagens and glycoproteins (ex. fibronectin and laminin)

Front 42

What interaction between cells and extracellular matrix is essential for correct formation of basement membranes?

Back 42

Integrin-laminin interactions

Front 43

______ are basement membrane proteins. These interact with _____

Back 43

-Laminins
-other basement proteins and integrins on the cell surface

Front 44

Laminins form ____ (which are built from ____ chains) that are stabilized by _____ bonds. Synthesis of these chains occur in the _____ and the assembly occurs in the _____

Back 44

-heterotrimers
-alpha, beta, gamma
-disulfide bonds
-ER
-golgi apparatus

Front 45

Junctional epidermolysis bullosa is cause by a mutation in _____. This can effect ____, can can cause symptoms such as ____

Back 45

-certain laminins and integrins
-the basement membrane below epidermis and mucosal membranes
-fragile skin that shows extreme blistering

Front 46

Tissue remodeling takes place during:

Back 46

-tissue differentiation (matrix composition changes) and cell migration (cells "cut through" the matrix)

Front 47

In order to remodel the matrix, what do cells secrete? And what does this do? What inhibits this?

Back 47

-they secrete matrix metalloproteinases (MMPs) that degrade the matrix proteins
-TIMPs (tissue inhibitors of metalloprteinases) inhibit MMPs

Front 48

What does the extent of tissue remodeling depend on?

Back 48

The ratio of MMPs (metalloproteinases) and TIMPs (Tissue Inhibitors of Metalloproteinases)
-both are secreted by cells

Front 49

Tumors frequently secrete large amounts of what to invade surrounding tissues?

Back 49

matrix metalloproteinases