Cell Matrix Proteins

Front 1

General contents of EM (extracellular matrix)

Back 1

Protein fibers + ground substance

Front 2

3 major classes of biomolecules in EM

Back 2

STRUCTURAL FIBROUS PROTEIN - collagen, elastin, fibrillin
SPECIALIZED PROTEIN - fibronectin + laminin, connect structural proteins to surface of cell
PROTEOGLYCANS- 5% protein + 95% glycosaminoglycans - long chains of repeating disaccharides, GAG's, sometimes called mucopolysaccharides, major component of ground substance

Front 3

Describe clinical involvement of EM

Back 3

1. Metastasis - migration of cancer cells through EM
2. Inflammation - RA + OA - changes in molecular components of EM
3. Aging - many changes in matrix

Front 4

Name two genetic defects of collagen

Back 4

Osteogenesis imperfecta
Ehlers-Danlos Syndrome

Front 5

Define collagen

Back 5

family of STRUCTURALLY SIMILAR EXTRA CELLULAR GLYCOPROTEINS most of which form FIBERS OF HIGH TENSILE STRENGTH and comprise most abundant protein in animals (25-30%)

Front 6

All collagen fibers are assembled from this protein

Back 6

TROPOCOLLAGEN - rigid, cross linked triple helical rods

Front 7

Collagens are secreted from

Back 7

Fibroblasts (all types of CT)
Osteoblasts
Chondroblasts

Front 8

There are _ characterized types of collagen

Back 8

19

Front 9

Which collagen type comprises 90 % of all collagens

Back 9

Type I

Front 10

How many chains are in collagen? Are they all the same?

Back 10

There are 3 chains. In some collagens all 3 chains are the same. In some collagens, 2 chains of one type and one chain of another type

Front 11

Which type of collagen is important component of basement membrane

Back 11

Type IV

Front 12

Describe amino acid composition of type I collagen

Back 12

Glycine is every 3d amino acid, also proline and hydroxyproline

Front 13

What is required to produce collagen

Back 13

Oxygen, alpha ketoglutarate and vitamin C

Front 14

How are chains syntesized

Back 14

With signal peptide which labels them for export

Front 15

How is collagen degraded

Back 15

Collagenase enzymes degrade collagen and macrophages digest fragments to amino acids

Front 16

Which type of collagen present in scar tissue

Back 16

Type III

Front 17

Describe osteogenesis imperfecta

Back 17

Brittle bone disease
1/20000 births
Results in abnormal bone fragility and deformity.

Front 18

Which collagen type defficient in osteogenesis imperfecta

Back 18

Type I is either abnormal or reduced

Front 19

Give types of OI

Back 19

Type I - most common and mildest
Type II - most severe - frequently lethal short after birth
Type III and IV - intermediate severity

Front 20

Describe Ehlers Danlos syndrome

Back 20

1 in 10000-15000
Hyperextensibility of skin and hypermobility of joints
Most types not life threatening

Front 21

Mode of inheritance for ED syndrome

Back 21

Autosomal dominant or recessive, more common autosomal dominant

Front 22

Mode of inheritance for OI

Back 22

Autosomal dominant

Front 23

Which type of ED syndrome is most severe

Back 23

Vascular - leads to rupture of bowel and arteries

Front 24

Which type of collagen affected in ED syndrome

Back 24

Type III

Front 25

Describe Alports syndrome, which collagen defective

Back 25

Type IV collagen defective (basement membrane collagen)
Symptoms may include hematuria, proteinuria and kidney failure
2nd most common cause of inherited kidney failure
Most patients develop kidney failure in early adulthood and also get progressive deafness
Mostly males

Front 26

Mode of inheritance for Alports

Back 26

Autosomal recessive or X linked

Front 27

Describe Dystrophic Epidermolysis Bullosa
Which collagen defective?

Back 27

Autosomal dominant or recessive
Defect of collagen type VII that forms anchoring fibrils to keep layers of skin together.
Breakage and blistering of skin

Front 28

Menke's syndrome

Back 28

X linked recessive
Mutations in gene encoding copper binding ATPase
Copper enters intestinal cells but is not transported further.
Result - Cu defficiency which is required as cofactor for lysine oxidase. Fewer covalent linkages between tropocollagens are formed.
Abnormal hair and cerebral degeneration + death in early infancy

Front 29

Scurvy is deficiency of what?

Back 29

Vitamin C, results in defective hydroxylation of Lys and Pro residues in collagen chains, making collagen instable

Front 30

Define elastin

Back 30

Forms fibers of rubbery nature, confers elasticity on tissue

Front 31

Elastin is prevalent where?

Back 31

Lungs
Walls of arteries
Skin
Elastic ligaments

Front 32

Elastin is synthesized by

Back 32

Fibroblasts

Front 33

Williams syndrome

Back 33

spontaneous mutation - 1/20000 births
Developmental disorder affecting CT in CNS
90% patients have deletions in elastin gene, resultin in insufficient elastin and narrowing of large elastic arteries - causes aortic stenosis

Front 34

Alpha 1 antitrypsin defficiency

Back 34

Autosomal recessive - 1 in 2500 births in Northern Europeans
Alpha 1 antitrypsin is an inhibitor of elastase, enzyme that hydrolyzes elastin,which is produced by neutrophils.
In patients with this defficiency, alveoli are destroyed by elastase which leads to emphysema, exacerbated by smoking which inhibits alpha 1 antitrypsin

Front 35

Define fibrillin

Back 35

Glycoprotein which is also secreted by fibroblasts, scaffolds depositions of elastin

Front 36

Marfans syndrome

Back 36

1 in 10-20000 births
Autosomal dominant
Mutation of gene encoding for fibrillin
Effects are in ocular, skeletal and cardiovascular systems.
Some people have detached lens and more often arachnodactyly.

Front 37

Fibronectin

Back 37

glues togethers cells and fibers of the matrix

Front 38

How does fibronectin play role in wound healing

Back 38

Becomes incorporated in a clot and attacts fibroblasts and endothelial cells

Front 39

Laminin

Back 39

is an important component of basal membrane
Provides structural support and glues other components of membrane to overlying cells.

Front 40

Junctional epidermolysis bullosa

Back 40

Defect in laminin
Blisterin of skin and mucous membranes

Front 41

Congenital muscular dystrophy

Back 41

Defect in laminin 2 - links muscle cell to EM
Causes muscle weakness

Front 42

Proteoglycans are basis for

Back 42

Ground substance of EM

Front 43

Proteoglycans are made of

Back 43

GAG - glycosaminoglycans (mucopolysaccharides) bound to core protein
Carbohydrate is main component and protein is minor

Front 44

Name 7 forms of GAG's

Back 44

HEPARIN - in granules of mast cells, liver, lung, skin, anticoagulant
HEPARAN SULFATE- located on cell surfaces and also extracellular, cell communication
CHONDROITIN SULFATE - most abundant GAG
DERMATAN SULFATE
KERATAN SULFATE I and II
HYALURONIC ACID - only non sulphated GAG

Front 45

Aggrecan is

Back 45

major proteoglycan of cartilage, interacts strongly with collagen, cotains hylauronic acid, chondroitin sulfate and keratan sulfate

Front 46

Syndecan and thrombomodulin are

Back 46

Integral transmembrane proteins, associated with actin cytoskeleton and interactin with fibronectin

Front 47

Mucopolysacchoridoses are disease associated with

Back 47

lysosomal storage diseases

Front 48

Characteristics of mucoplysaccharidoses

Back 48

Enzyme defficiency is generalized, affecting all organs
Inherited as autosomal recessive or X linked
Can be in both severe and mild forms
Most are not apparent at birht

Front 49

Defects in degradation of keratan sulfate and dermatan sulfate result in

Back 49

Skeletal deformities and other CT abnormalities

Front 50

Defects in heparan sulfate degradation cause

Back 50

Mental retardation and neurological degeneration

Front 51

Chondroitin sulfate and hyaluronic acid do not accumulate because

Back 51

they have alternative passages of degradation

Front 52

How do you diagnose mucopolysaccaridoses

Back 52

Presense of GAG's in urine