Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BPM DLA1 > Lecture 27 > Flashcards

Lecture 27 Flashcards

1
Q

What is extracellular matrix (ECM)?

A

Spaces in connetive tissue + interstitial matrix (space between cells) + basement membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Components of ECM

A

Fibers such as collagen and elastin

Ground substance - space-filler gluethat hold cells and fibers together

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Function of ECM

A
  1. Supporting framework
  2. Provide organized environment within which migratory cells can move and interact with one another
  3. Complex role in regulating the behavior of the cells it contacts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What does mechanical property of ECM depend on?

A

Amount of fibers
Type of fibers
Orientation of fiber

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is responsible for constant remodeling of ECM?

A

Matrix metalloproteinases (MMP) which need zinc and collagenases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Relationship between spread of cancer and matrix metalloproteinases

A

MMP is responsible for remodelling of ECM, so dysregulation of MMP can lead to spread of cancer cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

General characteristics of fibrous protein (4)

A

low water solubility
contain large amounts of repetitive secondary structure
long cylindrical shape for support
structural rather than dynamic role

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Characteristic of collagen (3)

A
  • insoluble proteins secreted from cell
  • found in all tissue and organs (but soft tissues have lower amount while structural organs have high)
  • major ECM protein
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Structure of collagen

A

triple-helix structure, composed of 3 long individual polypeptides (alpha-chains) organized parallel to a single axis

  • All 3 alpha chains are different (same length but different aa seq)&raquo_space; different mechanical properties
  • homotrimeric : 3 identical alpha chain
  • heterotrimeric : consisting of 2 or 3 distinct alpha chain
  • Alpha chain not same as alpha helix
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How is variation of alpha chains possible?

A

each alpha chain is encoded by separate gene, and different combinations of genes are expressed in different tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Primary structure of triple helix of collagen

A

1) repetitive primary structure rich in proline and lysine
- conserved sequence : Gly-X-Y-Gly-X-Y
Glycine :every 3rd position of chain which allow 3 helices to pack tightly together since it is small.
X: frequently proline which cause kinks in peptide chain, thus helps in forming helical structure (more proline, more kink, more strength)
Y: proline or lysine

  • End of alpha chains do not have conserved sequences
    2) Hydroxylation of proline and lysine by prolyl hydroxylase with its cofactor ‘ascorbate’ (occurs post-translationally prior to triple helix formation)
    3) Glycosylation of hydroxylysine by galactose or glucose (allow mineralization in bone)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Why are proline and lysine hydroxylated in collagen?

A

It increases stability of triple helix by maximizing interchain hydrogen bonding (more OH, more H-bond, more structural support)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Collagen biosynthesis

A
  1. Pre-pro-alpha-chain with ER signal sequence produced from translation
  2. Once inside ER, ER signal is removed and proline and lysine residues are hydroxylated.
  3. Sugars are added to selected hydroxylysine residues by glucose or galactose, forming pro-alpha-chains
  4. Intra and interchain disulfide bridges form between 3 pro-alpha-chains, facilitating helix formation., forming pro-collagen.
    * End of triple helix is nonhelical since it doesn’t have conserved seq, and they are called terminal extensions or propeptides
  5. Pro-collagen is contained vesicle and bud off from ER to golgi
  6. Pro-collagen is packaged and secreted to cell wall where it fuses and released into extracellular space.
  7. terminal extensions or propeptides are cleaved by C- or N-pro-collagen peptidases, forming tropocollagen. (still soluble in water and needs more modification)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Steps of fibillogenesis

A
  1. Synthesized collagens align in a staggered fashion each over-lapping its neighbors.
  2. Crosslinking takes place by action of lysyl oxidase, forming collagen fibrills
    - Lysyl oxidase react with amino group of lysine residue to change it into aldehyde group making it into allysine residue. Then, unmodified amino group of other lysine will react with aldehyde group of allysine to form a covalent bond = cross link (nucleophilic addition rxn)
    * Lysyl oxidase is copper-dependent
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Effect of copper deficiency on collagen fibril formation

A

lysyl oxidase which is responsible for crosslinking of collagen molecule is dependent on copper, so low copper supply leads to reduced cross-linking which leads to weaker stability and structural support of collagen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is gap between adjacent collagen molecule along fibril involved

A

Bone formation; site of bone mineralization (e.g. collagen in teeth and bone is impregnated with calcium phosphate)

Sugar attached to 5’-hydroxylysyl residues in the hole region may be involved in organization of fibril assembly.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Causes of collagenopathies

A
  1. Genetic defect in collagen genes
  2. Genetic defect in genes encoding enzymes involved in collagen biosynthesis (eg. prolyl hydroxylase)
  3. dietary deficiency of vitamin C
  4. Deficiency in copper i.e. Menkes disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What does vitamin C deficiency lead to in collagen fibril synthesis?

A

inibited hydroxylation of lysine and proline, leading to reduced interchain hydrogen bonding, leading to unstable collagen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Major characterization of scurvy

A

bone disease (children), haemorrhages, healing defects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Ehlers-Danlos Syndrome (EDS)

A

Disorder that disrupt collagen synthesis caused by defects in processing enzymes (e.g. lysyl hydroxylase or mutations in aa seq of collagen alpha chain)
- Affect connective tissue (skin, joint, blood vessel)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

2 Major forms of Ehlers-Danlos Syndrome (EDS)

A

Type I and II (Classical EDS) caused by mutation in genes COL5A1 and COL5A1 encoding type V collagen.
Charaterized by
- fragile hyperextensible skin
- joint hypermobility (dislocations)
- delayed wound healing
- hypotonia with delayer motor development
* Also caused by mutation in gene for type III collagen which leads to mutant chain that gets degraded or accumulated causing vascular problems.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Osteogenesis imperfecta

A 
8 different types
Type 1 (mildest) Type 2 (severest)
caused by mutation in COL1A1 and COL1A2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Osteogenesis imperfecta Type1

A

OI tarda

  • caused by mutation in COL1A1 which leads to reduced –synthesis of Type 1 collagen (alpha 1 &2 chains)(quantitative alterations)
  • often misdiagnosed as child abuse
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

menifestation of Osteogenesis imperfecta Type1

A
  • bone fractures during childhood & adolescence due to minor trauma
  • blue or grey tint to sclera
  • hearing loss in adulthood
  • retarded wound healing
  • rotation / twisting of spine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Osteogenesis imperfecta Type2

A

Congenita (Severe form)
mutation in either COL1A1 or COL1A2 gene (point mutation or exon rearrangements in regions coding for triple helical region)
- Glycine replaced by amino acid with bulky side chain which preventing triple helix formation
- deletion mutation of amino acids, leading to shortened chains that gets degraded (protein suicide) (qualitative defect)&raquo_space;> reduced level of type I collagen
- usually lethal in utero or after birth from pulmonary hypoplasia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Menifestation of Osteogenesis imperfecta Type2

A
  • multiple fracture
  • severe bone deformity
  • dark blue sclera
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What composes elastin fiber?

A

a central core of elastin

surrounding network of fibrillin micWhirofibril sheaths

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Which cell type produce elastin?

A

fibroblasts and smooth muscle cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Structure of elastin

A
  • a single polypeptide (long, fibrous, water-insoluble)
  • enriched in nonpolar amino acid (eg. glycine, alanine, valine)
  • not glycosylated, little hydroxyproline, no hydroxylysine
  • elastic fibers slide over one another for flexibility
  • associated with lungs, skin, uterus, blood vessels
  • dominant ECM protein in arteries
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Biosynthesis of elastin

A
  1. Produced as a tropoelastin from cell (precursor), then secreted into ECM
  2. Lysyl oxidase converts some amino group of lysines to aldehydes (allysine).
  3. 3 aldehyde groups of allysine react with 1 amino group of lysine to crosslink (aldol condensation rxn)&raquo_space; called desmosine cross-links which gives elastin a yellow color
  4. It links 4 elastin molecules forming extensive rubbery network of fibers
  5. Elastin fibers are deposited onto microfibil sheath which is made up of fibrillin (glycoprotein).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is microfibril sheath made up of

A

fibrillin 1 and 2 encoded by FBN-1 and -2 gene respectively

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Marfan syndrome cause and results

A

Disorder caused by defect in fibrillin 1 gene,
Results in
- changes in mechanical properties of ECM
- Loss of control of bioavailability of substances (eg. transforming growth factor beta which leads to excessive signaling that leads to excessive connective tissue growth, thus long limb formation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Manifestation of marfan syndrome

A
  • skeletal abnormalities (overgrowth of longbones, scoliosis)
  • ocular changes (dislocation, bilateral subluxation)
  • cardiovascular lesions (mitral valve prolapse, dilation of ascending aorta)
  • aortic haemorrhage
34
Q

Which amino acid is involved in N-linked glycosylation of protein?

A

asparagine

35
Q

What is lipid dolichol-PP? where is it located and how?

A

lipid that is bound in RER membrane, and it has many isoprene units which anchor it in RER membrane. A mannose-rich oligosaccharide is synthesized bound to lipid dolichol-PP.

36
Q

Step of N-glycosylation of protein

A
  1. protein polypeptide is extruded into rER,
  2. mannose-rich oligosaccharide is synthesized on dolichol-PP which is anchored in RER membrane.
  3. oligosaccharide is transferred in one step to a asparagine of protein.
  4. Trimming of sugar occurs in RER and golgi
  5. At golgi, further trimming at golgi makes high-mannose glycoproteins while addition of monosaccharide at golgi make complex glycoprotein.
37
Q

3 Targets of N-glycosylated glycoproteins

A
  1. Lysosome,
    2 secreted into blood
    3 incorporated into cell plasma membrane
38
Q

How is N-glycosylated glycoproteins incorporated into cell plasma membrane?

A

After synthesis, it is packaged into vesicle for delivery to membrane. In vesicle, N-glycosylated glycoproteins get integrated into vesicle’s membrane which then fuse with the cell membrane.

39
Q

Describe transport of N-glycosylated glycoproteins into lysosome

A

N-glycosylated glycoproteins in cis golgi is phosphorylated on mannose, receiving mannose 6-P marker by phosphotransferase. Then at trans golgi, the marker binds to mannose6-P receptor which gets packaged into vesicle for transport into lysosome. Then as N-glycosylated glycoproteins reaches lysosome, receptor gets recycled and cleavage of phosphate of marker activates enzyme inside the lysosome.

40
Q

What is I-cell disease?

A

Deficiency of phosphotransferase leads to lack of mannose6-P marker on N-glycosylated glycoproteins, thus lysosomal enzymes are lacking in lysosomes, leading to lack of degradation and accumulation of different molecules forming inclusion bodies. N-glycosylated glycoproteins is instead secreted and found in plasma and urine.

41
Q

How can I cell disease be diagnosed?

A

made by detection of inclusions in lymphocyte or cultured skin fibroblasts which is confirmed by lysosomal enzyme activity in blood plasma.

42
Q

Children who have I-cell disease have common features with those who have mucopolysaccharidoses or sphingolipidoses. So I-cell is grouped as…..?

A

mucolipidosis type III

43
Q

Difference between proteoglycan and glycoprotein

A

proteoglycan

  • mainly special sugars (GAGs) and small protein
  • O-glycosyltaion of core protein

Glycoprotein

  • mainly protein and small sugars which are branched
  • O- and N-glycosylation
44
Q

Which amino acid is involved in O-linked glycosylation? (3)

A

serine, threonine , hydroxylysine (in collagen)

45
Q

Describe O-glycosylation of protein

A
  1. protein is synthesized and extrudes into RER’s lumen.
  2. First sugar is transferred and linked directly to OH-group of serine, threonine, or hydroxylysine residues by glycosyl transferases which are bound to Golgi membrane (happens in golgi)
  3. Activated sugars are then individually linked to glycoprotein by enzymes that act in a specific order.
    (glycosyltransferase recognize the actual structure of growing oligosaccharide as their substrate and link the correct sugar to glycoproteins)
46
Q

Use of O-glycosylation (4)

A

synthesis of proteoglycans
glycocalyx
blood group substances
mucins

47
Q

Which sugar is linked to blood Type O Gal of H substance ?

A

No sugar is linked,

48
Q

Which sugar is linked to blood type A gal of H substance?

A

GalNAc linked

49
Q

What is H substance in blood type?

A

Basic glycoprotein structure which is made up of Fuc, Gal, GlcNAc and R (protein or lipid)

50
Q

Which sugar is linked to blood type B gal of H substance?

A

Galactose

51
Q

Is mucin glycoprotein or proteoglycan? what is its composition?

A

It is glycoprotein even though 50% is carbohydrate. It is a special glycoprotein that contain more carbohydrate than other glycoproteins.

52
Q

Is mucin O-linkage or N-linkage?

A

O-linkage, this protein is rich in serine, threonine.

53
Q

What is salivary mucins?

A

It contain mainly only one N-acetylglucosamine linked to serine or threonine residues. Then this sugar binds to NANA (sialic acid) which results in mucins with many negative charges.

54
Q

Use of mucin

A

Mucin combines with water to form mucus which protects and lubricates many internal body surface

55
Q

What makes up glycocalyx?

A

glycoproteins and glycolipids

56
Q

Function of glycocalyx

A

cell-cell recognition
sieving barrier
inhibition of platelet adherence
prevention of leukocyte adhesion

57
Q

Disadvantage of glycocalyx

A

It provides unwanted binding and adhesion at the cell surface with viruses and bacteria, allowing first step of infection.

  • virus bind to glycoprotein
  • bacterial toxin bind to surface glycolipid
    ex) e.coli and helicobacter pylori
58
Q

Interaction between ecoli and glycocalyx

A

E.coli attaches to mannose residues that are incorporated into plasma membrane of human cheek cells, causing bacterial infection

59
Q

Interaction between helicobacter pylori and glycocalyx

A

It attaches to gastric surface, which leads to ulcers by interacting with specific blood group antigen of gastric epithelium.

60
Q

Difference between glycosaminoglycan (GAG) and proteoglycan

A

GAG are long, unbranched chains of negatively charged sugars and are often surfated. Proteoglycan contains these GAGs (90%) and they are part of ECM.

61
Q

Structure of Glycosaminoglycan (GAG)

A

Repeating disaccharide unit made up of acidic sugar (glucuronic acid or iduronic acid) and amino sugar (glucosamine or galactosamine) which can be acetylated.

  • 1st posistion : acidic sugar
  • 2nd position : amino sugar
62
Q

How does structure of GAG contribute to its resilience?

A

GAG have strong negative charge from carboxyl and sulfate groups. It can bind large amounts of water producing a gel-like matrix which is part of ECM.
So it reacts to compression with squeezing water out of itself and to relaxation with absorbing the water.

63
Q

Function of hydrated GAGs(4)

A
  1. flexible support of ECM
  2. Molecular sieve
  3. Lubricants
  4. Shock absorber
64
Q

Different types of GAGs (6)

A
  1. Chondroitin sulfate
  2. Keratin sulfate
  3. Dermatan sulfates
  4. Heparan sulfate
    5 Heparin
  5. Hyaluronic acid
65
Q

What is chondroitin sulfate? Where can it be found?

A

A type of GAG which is the most abundant GAG in the body.
Chondroitin is sulfated in position 4 or 6 (Chondroitin 6-sulfate or chondroitin 4-sulfate)
Found in cartilage, bone, ligaments, aorta

66
Q

Why is keratin sulfate special GAG?

A
  • it contain a sulfated galactose in position-1 (usually acidic sugar such as glucuronic acid or iduronic acid).
  • This is the most heterogenous regarding their sugars.
67
Q

Where is keratin sulfate found?

A

cartilage and cornea

68
Q

Composition of chondroitin sulfate

A

1st position : glucuronic acid

2nd position : N-acetyl galactosamine (sulfated)

69
Q

Composition of keratin sulfate

A

1st position : sulfated galactose

2nd position : N-acetyl glucosamine (sulfated)

70
Q

composition of dermatan sulfate

A

1st position : iduronic acid

2nd position : N-acetyl galactosamine (sulfated)

71
Q

Where can dermatan sulfate found?

A

skin, blood vessel, heart valve

72
Q

Composition of heparan sulfate

A

1st : glucuronic acid or iduronic acid (sulfated)

2nd : N-sulfate glucosamine (2 sulfate) - no acetyl

73
Q

Where is heparan sulfate found?

A

in base membrane or on cell surfaces for cell-cell recognition

74
Q

Composition of heparin

What is special about it?

A

contain many iduronyl sulfates
1st iduronyl sulfate
2nd : N-sulfate glucosamine (sulfate) no acetyl
* GAG with largest amount of sulfate and negative charges

75
Q

Where can heparin be found?

A

It is not extracellular but it is found in mast cells that line arteries of lung, liver and spleen.

76
Q

Function of heparin

A

Anticoagulant, ending blood clotting by facilitating inhibition of thrombin.

77
Q

Composition of hyaluronic acid

What is special about it

A

1st: hlucuronic acid
2nd: N-acetyl glucosamine
* Not sulfated
* Not covalently attached to a protein, but connected to the core proteins via link proteins

78
Q

How is hyaluronic acid synthesized unlike other GAGs

A

it is synthesized step by step directly into extracellular space, providing extracellularly the central strand in proteoglycan aggregates.

79
Q

Where is hyaluronic acid found? (4)

A

Vitreous humor of eye
Synovial fluid of joint
Cartilage
Loose connective tissues

80
Q

Roles of hyaluronic acid (3)

A

It facilitates cell migration in :
embryogenesis (neural tube closure)
morphogenesis
wound repair

  • a central strand in proteoglycan aggregates in ECM where all central protein of proteoglycan monomer linked to hyaluronic acid via link protein
    (these proteoglycan are formed intracellularly by O-glycosylation of core protein and then released into ECM)
81
Q

What is the GAG linkage region that links Serine or threonine side chain of core proteins with repeating disaccharide unit?

A

trihexoside linker region (xylose-galactose-galactose)

82
Q

Role of proteoglycan aggregates in ECM

A

The aggregates have hyaluronic acid as central GAG strand and serve as shock absorber and lubricant.

BPM DLA1 (47 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions