Connective Tissue

Question 1

Proteoglycans

Answer 1

Core protein is covalently attached to multiple, long/linear chains of glycosaminoglycans

Question 2

Where are proteoglycans found?

Answer 2

Synovial fluid, arterial walls, bone/cartilage, ocular virtuous humor, and is a major component of the extra cellular matrix

Question 3

Functions of proteoglycans

Answer 3

Molecular sieves (due to largeness), give some flexibility to substances

Question 4

Glycosaminoglycans

Answer 4

Repeating disaccharide units found on proteoglycans Usually contain a hexosamine and uronic acid

Question 5

How do the types of glycosaminoglycans differ?

Answer 5

Monosaccharides in repeating units change

Question 6

Which glycosaminoglycan does not link covalently?

Answer 6

Hyaluronic acid

Question 7

What proteins to 5 of 7 glycosaminoglycans covalently link to?

Answer 7

Serine and Threonine

Question 8

Which amino acid does keratan sulfate I attach to?

Answer 8

Asparagine

Question 9

How does hyaluronic acid associate with proteins?

Answer 9

Noncovalent linkage

Question 10

Synthesis of proteoglycans

Answer 10

1. Sugar attaches to serine/threonine
2. UPD-sugar glycosyltransferases transfer monosaccharides from nucleotide-linked sugar to receptor
3. 2 glycosyltransferases alt adding monosac.
4. Sulfate groups added after sugars by PAPS
5. Secreted and forms into ECM

Question 11

Proteoglycan aggregate

Answer 11

Formed by noncovalent interactions b/t the core protein and hyaluronic acid

Question 12

Glycoproteins

Answer 12

• Usually shorter carb chains than proteoglycans
• Carb portion is usually branched and not made of repeating disaccharides
• Make up most of the proteins circulating in the blood

Question 13

Glycoprotein synthesis

Answer 13

1. Carb monomers are added to protein (lumen of ER/Golgi)
2. sugar added via O-linkage (ser, thr) or N-linkage (asn)
3. Carb side chain extended by sequential addition of sugar residues to nonreducing end

Question 14

O-Linked Glycosides

Answer 14

• Begin w/ N-acetyl-galactosamine to specific ser or thr side chain on protein

Question 15

N-linked Glycosides

Answer 15

• Lipid-linked oligosaccharide is contracted (dolichaol molecules on the membrane)
• sugars added to dolichol by membrane bound glycosyltransferases
• Oligosaccharides transferred from dolichol to asn by protein-oligosaccharide transferase in ER

Question 16

Degredation of proteoglycans and glycoproteins

Answer 16

• Lysosomes endocytose the molecules
• Glycosidases degrade carb portion of molecules

Question 17

Endoglycosidase

Answer 17

Cleaves the carb chain to shorter oligosaccharides

Question 18

Exoglycosidase

Answer 18

Removes sugar residue from the nonreducing end

Question 19

Collagen Structure

Answer 19

• Triple helix made of 3 alpha chain, left handed helices (3 residues per turn)
• Chains wound together (right handed) and H-bonds stabilize
• Glycine-X-Y is repeated pattern

Question 20

Proline and hydroxyproline: role in collagen helices

Answer 20

Increases rigidity in collagen helices

Question 21

Synthesis of Collagen

Answer 21

1. Preprocollagen synth. (has a signal sequence and polypeptide extension removed from N&C terminals)
2. triple helix formed from C-terminal bc had the ability to form both inter- and intrachain disulfide bonds

Question 22

Propel hydoxylase

Answer 22

• Hydroxylates the proline molecules, making necessary hydroxyproline
• Vitamin C and α-ketoglutarate are cofactors

Question 23

Lysine/hydroxylysine

Answer 23

• Formed via Lysyl hydroxylase
• Either lysine or hydrated form can be in Y position

Question 24

Interruptions

Answer 24

• Areas of globular structures interspersed in the triple helical structure
• Lack Gly-X-Y form
• Ex: Collagen IV

Question 25

Type I and V of collagen

Answer 25

Skin, bone, tendon, blood vessels, cornea

Question 26

Type II of Collagen

Answer 26

Cartilage, intervertebral disks, nitrous body

Question 27

Type III of Collagen

Answer 27

Blood vessels, fetal skin

Question 28

Type IV of Collagen

Answer 28

Basement membrane

Question 29

Ehlers-Dalos Syndrome

Answer 29

* Inheritied genetic disorder affecting collagen * Signs: hyperflexibility of skin, abnormal tissue fragility, increased joint mobility * 10 types

Question 30

Type IV of Ehlers-Dalos Syndrome

Answer 30

Most serious type that can cause ruptures of the bowl arteries due to abnormalities in type III collagen

Question 31

Type VI of Ehlers-Dalos Syndrome

Answer 31

Hysyl hydroxylase deficiency results in joint hypermobility/ocular rupture

Question 32

Type VIIC of Ehlers-Dalos Syndrome

Answer 32

Procollagen N-proteinase deficiency results in joint hypermobility (from abnormally thin, irregular collagen fibrils)

Question 33

Alport Syndrome

Answer 33

* x and autosomal linked * Affects Type IV collagen fibers * Signs: hematuria, can developed ESRD due t orenal basal abnormaility

Question 34

Scurvy

Answer 34

* Vitamin C deficiency that affects collagen production (prolysyl and lysyl hydroxylase cofactor) * Signs: bleeding gums, subcutaneous hemorrhages, poor wound healing

Question 35

Elastin

Answer 35

Add elastic properties of extensibility and elastic recoil in tissue (stretching without tearing)

Question 36

Synthesis of Elastin

Answer 36

* synthesized in a single tropoelastin molecule * No extention peptides in C/N terminals, Gly-X-Y, triple helices, or card portions

Question 37

Lysyl oxidase

Answer 37

* involved with collagen processing * Also deanimates lysyl residues from the tropoelastin

Question 38

Desmosines

Answer 38

* Major cross-link of elastin (CL is unique to elastin) * 3 lysine-derived aldehydes w/ an unmodified lysine * CL makes it highly insoluable and extremely stable

Question 39

Williams syndrome

Answer 39

* Developmental disorder affecting CNS and connective tissue * 90% of subjects have elastin deletion – Probable cause of aortic stenosis found in condition

Question 40

Fibrillin

Answer 40

* Large glycoprotein that is a structural component of microfibirls * Secreted into the ECM to be incorporated into insoluable microfibrils * Provides a scaffold for deposition of elastion

Question 41

Marfan Syndrome

Answer 41

* Autosomal dominant – affects connective tissue * Signs: Tall, long digits, hyperflexibility of joints, cardiovascular problems * Fibrillin gene is deleted/missense mutations

Question 42

Fibronectin

Answer 42

* Soluble glycoprotein found in large amounts in the ECM * Dimmer joined by disulfide bonds near C-terminal * Arg-Gly-Asp sequence (RGD) that binds to integrin * 7 binding sites doe heparin, fibrin, collagen, DNA, cell surface proteins

Question 43

Laminin

Answer 43

* 3 distinct polypeptide chains linked together to form elongated cruciform shape * Binding site for Collagen IV, heparin, integrin * Primary component of basal lamina

Question 44

Basal lamina components

Answer 44

Laminin, enactin, type IV collagen