Biochemistry Of connective Tissue ECM

Question 1

Fibrin-forming types of collagen

Answer 1

Type 1-3

Question 2

Type 1 collagen

Answer 2

Forms fibrils in skin,bone,tendon, blood vessels and cornea

• made up of 2 (a1) and 1 (a2) chains

Question 3

Type 2 collagen

Answer 3

Fibrin-forming in cartilage, intervertebral disks, vitreous bodies

-made up of 3 (a1) chains

Question 4

Type 3 collagen

Answer 4

Forms fibrils in blood vessels, skin and muscle

Question 5

Network-forming types of collagen

Answer 5

Types 4 and 8

Question 6

Type 4 collagen

Answer 6

Network-forming collagen found in basement membrane

Question 7

Type 8 collagen

Answer 7

Network-forming collagen found in corneal and vascular endothelium

Question 8

Fibril-associated collagen types

Answer 8

Types 9 and 12

Question 9

Type 9 collagen

Answer 9

Fibril-associated collagen found in cartilage

Question 10

Collagen type 12

Answer 10

Fibril-associated collagen found in tendons and Ligaments

Question 11

Collagen basic structure

Answer 11

Fibrous protein shaped in via 3-(a) chains. Stabilized by intrachained H-bonds.

• each (a)-chain is encoded by a different gene
• Rich in Gly and Pro amino acids.
• every 3rd amino acid is a “Gly”

Question 12

Hydroxylated amino acids found in collagen

Answer 12

HydroxyPROLINE

hydroxyLYSINE

• requires, oxygen, iron and vitamin C (ascorbate) to hydroxylate amino acids*
• occurs in rough ER

Question 13

Cross linking of collagen

Answer 13

Cooper-containing extracellular enzymes delaminates lysine and hydroxylysine residues to reactive aldehyde groups.

These aldehyde groups can cross link with each other in mature collagen fibers, further promoting tension strength.

Question 14

Collagen synthesis occurs where?

Answer 14

Endoplasmic reticulum = procollagen (immature) formation

Extracellular matrix = mature collagen

Question 15

Steps of transforming procollagen into collagen in the extracellular matrix

Answer 15

N and C proteinases cleave propeptides

• collagen fibrils are formed
• Lysyl oxidase begins formation of aldehyde groups that covalently crosslink with each other.

Question 16

Collagenopathies

Answer 16

Genetic diseases due to defects in one of the steps of collagen fiber synthesis

Question 17

Elastic fiber composition

Answer 17

Inner core of elastin protein surrounded by microfibils of fibrilin

• very interconnected via cross linking, allowing it to “bounce back” to its original structure.
• lysyl oxidase is the enzyme that does the cross-linking.

Question 18

Fibrillins

Answer 18

Glycoproteins that provide scaffold for elastin

major group is Fibrillin-1

Question 19

Laminin

Answer 19

Large cross shaped glycoproteins that consists of 3 polypeptide chains encoded by different genes (heterotrimer)

Functions to hold components of the basement membrane together, trigger physiological responses, growth and movement of the body.

Quarternary protein

Question 20

Fibronectin

Answer 20

large protein formed by two polypeptide chains linked by disulfide bonds. Binds to heparan sulfate proteoglycans.

Functions to glue cells to fibrous matrix in ECM, movement of cells In embryogenesis and metastasis of cancer

Most abundant multi-adhesive protein

Question 21

Proteoglycans vs Glycoproteins

Answer 21

Proteoglycans: high carb, low protein percentages
(95% carbs: 5% proteins)
Heteropolysaccharide chains

Glycoproteins: high protein, low carb percentages

Question 22

Proteoglycans functions

Answer 22

Gel-like matrix that provides flexible support in ECM and lubricating properties.

Influences movement of material through ECM

Lubricating properties of mucus

Question 23

Glycosaminoglycans (GAGs)

Answer 23

Large complexes of negatively charged heteropolysaccharide chains.

Formed by a repeating disaccharide unit of an acidic sugar and an N-acetylated amino sugar.

Attracts water via the N-acetylated sugar

6 major classes Sorted by composition, type of glycosidic linkage and degree/location of sulfate units.

Question 24

How is collagen synthesized

Answer 24

Synthesized in the cells of CT in their endoplasmic reticulum.

Ribosomes synthesize the individual chains of collagen fibers.

Move to the lumen of the ER and hydroxylation and glycosylation of the proline/lysine residues
Forms the procollagen

Moves to extracellular matrix via transport vesicles Where the terminals of procollagen are cleaved

Lysyl oxidase then binds procollagen fibers together to generate mature collagen

Question 25

Structures in proteoglycans aggregates

Answer 25

GAGs A core protein Hyaluronic acid A link protein

Question 25

Chondroitin 4-6 sulfate

Answer 25

Class of GAG Most abundant GAG in the body that is found in cartilage, tendons ligaments and aorta. From aggregates via noncovalent bonds with hyaluronic acid

Question 26

Keratan sulfates

Answer 26

Class of GAG Most heterogenous GAG containing additional monosaccharides Found in cornea (subtype 1) and loose connective tissue (subtype 2). Aggregates with non-covalent bonding with chondroitin sulfate

Question 27

Hyaluronic acid

Answer 27

Class of GAG NOT sulfates and not covalently bound to any protein. Found in bacteria as well as animal tissue Serves as lubricant and shock absorber Found in synovial fluid of joints, vitreous humor of the eye, loose CT and cartilage.

Question 28

Dermatan sulfate

Answer 28

Class of GAG Found in skin, blood vessels and heart valves

Question 29

Heparin

Answer 29

Class of GAG (A)-sulfur linkages joins disaccharides, only one to do so ONLY INTRACELLULAR GAG, in Mast cells exclusively Serves as an anticoagulant

Question 30

Heparan sulfate

Answer 30

Class of GAG Found in basement membrane and as a ubiquitous component of cell surfaces.

Question 31

Metabolism of GAGs

Answer 31

Synthesized in this order - core protein - carb chains - sulfonation post-modification in carb chains Degradation: By endocytosis and Lysosomes

Question 32

Chondrosytrophies

Answer 32

Defects in the sulfonation of GAGs (affects synthesis) Autosomal recessive Causes dwarfism

Question 33

Mucopolysaccharidoses

Answer 33

Deficiency of lysosomal hydrolysis in heparan sulfate or dermatan sulfate (affects degradation) Autosomal recessive -except for Hunter syndrome subtype (X-linked recessive) Progressive disorder with GAGs accumulating in lysosomes Oligosaccharides in the urine is present Causes skeletal and ECM deformities and mental retardation.

Question 34

Hurler syndrome (MPS 1)

Answer 34

Subtype of mucopolysaccharidoses Deficient of L-iduronidase (cant degrade dermatan and heparan sulfate) Affects corneas of eyes and coronary arteries leading to ischemia. Coronal clouding Treated by bone marrow transplants and enzyme replacement therapy Most severe form and one of the most common types

Question 35

Hunter syndrome (MPS 2)

Answer 35

Subtype of mucopolysaccharidoses iduronate sulfatase deficiency (cant degrade dermatan and heparan sulfate) X-linked recessive Mild-severe physical deformities (specifically rashes) No coronal clouding. Treated via enzyme replacement therapy One of the most common types

Question 36

Sanfilippo Syndrome (MPS 3)

Answer 36

Affects various steps of removing sulfate residues from heparan sulfate Severe nervous system disorders and developmental disorders No coronal clouding

Question 37

Sly syndrome (MPS 7)

Answer 37

Glucuronidase deficiency (impairs degradation of dermatan and heparan sulfate) Hepatosplenomegaly, Skeletal deformity, short store and corneal clouding