Biochemistry - Extracellular Matrix And Lysosomal Diseases

Front 1

What is the central role of the ECM?

Back 1

regulating basic cellular processes like proliferation, differentiation, migration and cell-cell recognition

Front 2

Changes in the composition of the ECM can lead to what?

Back 2

chronic diseases such as arthritis, atherosclerosis, fibrosis and cancer

Front 3

What does the ECM contain?

Back 3

fibrous, structural proteins (collagen and elastin), specialized proteins (fibrillin, fibronectin and laminin) and the gel-forming group of proteoglycans

Front 4

The ECM prevents the movement of what?

Back 4

microorganisms and cancer cells

Front 5

What is the most abundant fibrous protein

Back 5

collagen, which represent 30% of total body protein mass

Front 6

What is elastin?

Back 6

Elastin is a network of elastic fibers that allows the flexibility for blood vessels, lungs, ligaments and skin. It has a long half-life

Front 7

Lysosomal enzyme deficiencis in the degradation of GAGs leads to what? Glycoproteins? Glycogen? Glycolipids?

Back 7

mucopolysaccharidoses, oligosaccharidoses, Pompe's disease, sphingolipidoses

Front 8

How many genes transcribe collagen?

Back 8

Two genes are transcribed to eventually form three pro-alpha chains

Front 9

Three pro-alpha chains will be used to form what?

Back 9

procollagen

Front 10

What is found in each third position of collagen?

Back 10

glycine

Front 11

Besides glycine, what other amino acid is found in collagen?

Back 11

proline. Proline leads to "kinks" in the protein chain

Front 12

What gives collagen stability?

Back 12

hydroxyproline

Front 13

The hydroxylation of lysine residues can be used for what?

Back 13

glycosylation with glucose or galactose or both

Front 14

Collagen is translated to mRNA in the cytosol into what?

Back 14

prepro-alpha polypeptide chains

Front 15

What is the next step after formation of prepro-alpha polypeptide chains?

Back 15

Selected proline and lysine residues are hydroxylated

Front 16

What is the next step after hydroxylation?

Back 16

Selected hydroxylysine residues are glycosylated with glucose and galactose

Front 17

Glycosylation is followed by what?

Back 17

Three pro-alpha chains assemble. Intrachain and interchain disulfide bonds form at the C-terminal propeptide extension

Front 18

How is the triple helix formed?

Back 18

A triple helix is formed by zipper-like folding

Front 19

After the triple helix is formed, what happens next?

Back 19

The procollagen molecule is secreted from a Golgi vacuole into the extracellular matrix

Front 20

What cleaves the N-terminal and C-terminal ends of procollagen?

Back 20

procollagen peptidases

Front 21

What enzyme hyroxlates proline and lysine residues?

Back 21

prolyl and lysyl hydroxylases

Front 22

What is required by prolyl and lysyl hydroxylases?

Back 22

molecular oxygen and Vitamin C as coenzyme

Front 23

What stabilizes the three strands?

Back 23

Hydroxy prolyl groups stabilize the three strands by hydrogen bonds

Front 24

Deficiency of Vitamin C can lead to what?

Back 24

Scurvy: bleeding gums, hemorrhages, poor wound healing

Front 25

Self-assembly of collagen fibrils in the extracellular space is followed by what?

Back 25

covalent cross-linking using lysyl and modified lysyl residues

Front 26

What is needed for cross-linkage?

Back 26

lysyl oxidase

Front 27

Lysyl oxidase forms what in collagen?

Back 27

allysine or hydroxy-allysine residues

Front 28

What cofactor is needed for lysyl oxidase?

Back 28

copper

Front 29

Copper deficiency can lead to what?

Back 29

aneurysms

Front 30

What is Ehlers-Danlos Syndrome and what are the characteristics?

Back 30

Group of more than 20 genetic defects in collagen synthesis. It can lead to hypermobility of the joints, fragility of skin and vascular vessel walls (rupture) and hyperextensibility of skin

Front 31

What are some possible causes of Ehlers-Danlos Syndrome?

Back 31

defective hydroxylations, defective cross-linking or defective cleavage of the propeptides

Front 32

What is osteogenesis Imperfecta (OI)?

Back 32

Genetic defect in collagen synthesis

Front 33

What is Type I OI?

Back 33

osteogenesis imperfecta tarda: early infancy, long bone fractures, blue sclera

Front 34

What is Type II OI?

Back 34

osteogenesis imperfecta congenita: death in utero or neonatal

Front 35

What is elastin?

Back 35

Elastin is a protein with rubber-like properties in lungs, walls of large arteries, and elastic ligaments

Front 36

How many genes are used to form tropoelastin?

Back 36

One gene is used to form tropoelastin which is a linear polypeptide

Front 37

Cross-links of elastin include what?

Back 37

desmosine

Front 38

One third of the amino acids in elastin is what? What other amino acids does it contain?

Back 38

glycine. alanine and valine

Front 39

What are the similarities and differences between elastin and collagen?

Back 39

It is also rich in proline and lysine but it contains only a little hydroxy-proline and no hydroxy-lysine

Front 40

Tropoelastin contains two types of alternating domains. What are they?

Back 40

hydrophilic and hydrophobic regions which seem to alow stretching and relaxing especially in lung tissue

Front 41

Marfan's Syndrome is a genetic defect related to what?

Back 41

fibrillin-1 protein which leads to defective structures in the skeleton, eye and cardiovascular system

Front 42

Desmosine is formed by what?

Back 42

three allysine and one lysine residue. It leads to the yellow color of elastin

Front 43

What protein protects elastin?

Back 43

alpha 1 antitrypsin (AAT)

Front 44

What is the function of AAT?

Back 44

Mostly synthesized by the liver and is released into the blood to inhibit neutrophil elastase that is found in low levels (released from neutrophils) in the alveoli of the lung

Front 45

A genetic defect of the release of AAT (N-glycosylation) from the liver can lead to what?

Back 45

liver cirrhosis and emphysema, especially in smokers

Front 46

Where does the degradations of GAGs, glycoproteins and sphingolipids take place?

Back 46

In lysosomes where specific enzymes remove the groups in sequence of the reverse order of synthesis, "last on, first off"

Front 47

Tay-Sachs' disease, Gaucher's disease, and Niemann-Pick disease are examples of what?

Back 47

Sphingolipidoses

Front 48

What is Tay-Sachs' Disease?

Back 48

Hexosaminidase A deficiency. Cherry-red macula and accumulation of ganglisode GM2 with onion-shell inclusions. Mental retardation, blindness, seizures, fatal

Front 49

What is Gaucher's Disease?

Back 49

Glucocerebrosidase deficiency, glucocerebrosides fill enlarged lysosomes. "Crumpled tissue paper"
Infantile form; mental retardation
Adult form (99%): tratable by IV enzyme infusion, no brain damage, but damage of liver, osteoporosis and sever splenomegaly

Front 50

What is Niemann-Pick Disease?

Back 50

Deficiency of sphinomyelinase.
Type A: severe infantile form with rapid neurodegeneration and severe mental retardation leading to death early in childhood
Type B: chronic form that causes mostly damage to lungs, spleen, liver, bone marrow. Life-expectancy only to early adulthood