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Medical Biochemistry > GAGs and Proteoglycans > Flashcards

GAGs and Proteoglycans Flashcards

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USMLE® Step 1 flashcards
1
Q

What are glycosaminoglycans (GAGs)?

A

Heteropolysaccharides made up up repeating disaccharide units

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2
Q

What type of matrix do GAGs have?

A

Gel- like

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3
Q

What causes GAGs to have a Gel- like matrix?

A

H20 binding properties

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4
Q

What general part of the body do GAGs form?

A

Body’s ground substance

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5
Q

What type of properties do GAGs have?

A

lubricating properties

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6
Q

What do GAGs stabilize and support?

A

cellular and fibrous components of tissues

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7
Q

What do GAGs help to maintain in the body?

A

Water and salt balance

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8
Q

What causes GAG molecules to fan outwards and repel adjacent molecules?

A

Strong negative charges

-COO and -OSO3

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9
Q

What type of shell surrounds each GAG molecule?

A

hydrated shell

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10
Q

What are the functions of GAGs?

A 
cell-shape maintenance
adhesion
migration
cell-cell communication
source of growth factors
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11
Q

Where are GAGs found?

A

Extracellular (most)

except Heparin

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12
Q

What property of GAGs accounts for the resilience of synovial fluid and vitreous humor of the eye?

A

Reverse compressibility

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13
Q

GAGs are also named what?

A

mucopolysaccharides.

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14
Q

What are proteoglycans?

A

Proteoglycans contain many GAGs linked to a protein chain

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15
Q

Do proteoglycans mainly contain sugars or protein?

A

They contain mainly

sugars (95%) and a small amount of protein.

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16
Q

What is the structure of a proteoglycan monomer?

A

Has a central core protein and via a trihexoside, many disaccharide units are linked.

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17
Q

What is Hyaluronic acid synthesized by?

A

Integral membrane protein

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18
Q

The integral membrane protein in hyaluronic acid synthesis does what?

A

elongates the GAG as it is released via ABC-transporters into the extracellular space

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19
Q

What repeating disaccharide units make up GAGs?

A

[acidic sugar - amino sugar]

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20
Q

What are the amino sugars that can make up GAGs?

A

D-glucosamine or

D-galactosamine

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21
Q

What are the acidic sugars that make up GAGs?

A

D-glucuronic acid or C-5 empimer: L-iduronic acid exception is Keratin Sulfate)

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22
Q

Why is Keratin Sulfate an exception when it comes to the acidic sugar unit?

A

Galactose instead of acidic sugar

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23
Q

What makes up Hyaluronic acid?

A

D-glucuronic acid + N-acetyl-D-glucosamine

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24
Q

Where is Hyaluronic acid found?

A

Synovial fluid
vitreous humor
ECM of loose connective tissue

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25
Q

Is Hyaluronic acid sulfated?

A

No (only GAG without sulfate)

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26
Q

Is Hyaluronic acid covalently attached to proteins in proteoglycans?

A

No (only GAG not)

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27
Q

What makes up Chondroitin Sulfate?

A

D-glucuronic acid + N-acetyl-D-galactosamine

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28
Q

Where is chondroitin sulfate found?

A

Cartilage
Bone
heart valves

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29
Q

What is the most abundant GAG?

A

Chondrotin Sulfate

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30
Q

What makes up Keratin Sulfate?

A

D-Galactose + N-Acetyl-D-Glucosamine

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31
Q

Where is Keratin Sulfate found?

A

Cornea
Bone
Cartilage

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32
Q

Typically, Keratin Sulfate is found aggregated with what?

A

Chondroitin sulfates

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33
Q

What makes up Dermatan Sulfate?

A

L-iduronic acid + N-acetyl-D-galactosamine

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34
Q

Where is Dermatan Sulfate found?

A

Skin
Blood vessels
heart valves

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35
Q

Which GAGs are found in heart valves?

A

Dermatan Sulfate

Chondroitin Sulfate

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36
Q

What releases Hyluronic acid (during synthesis) into the extracellular space?

A

ABC transporters

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37
Q

What makes up Heparin and Heparan sulfate?

A

D-glucoronic/L-iduronic acid
+
N-acetyl/N-sulfo - D-glucosamine

38
Q

Where is Heparin found?

A

Intracellular granules of mast cell lining the arteries of lungs;
Liver and skin

39
Q

Which is more sulfated, Heparin or Heparan Sulfates?

A

Heparin

40
Q

Where are Heparan Sulfates found?

A
  • Basement membranes

- components of cell surfaces

41
Q

Which contains more acetylated glucosamine, Heparin or Heparan Sulfates?

A

Heparan Sulfates

42
Q

What makes up the tri-hexoside which links the GAG and protein?

A

Xylose-Galactose-Galactose

43
Q

What links the linkage region of a GAG to the core protein?

A

Serine side chain

44
Q

What makes up proteoglycans in cartilage?

A

Chondroitin Sulfate and Keratan Sulfate attached to a protein core

45
Q

Where are GAGs synthesized?

A

ER and Golgi

46
Q

What catalyzes elongation of GAGs in the Golgi?

A

glycosyl transferases

47
Q

What are the steps in proteoglycan synthesis?

A

1) Synthesis of amino sugar
2) Synthesis of acidic sugar
3) Synthesis of core protein
4) Synthesis of carbohydrate chain
5) Addition of sulfate group

48
Q

During proteoglycan synthesis, what is the sulfate donor?

A

PAPS

3-Phosphoadenosine 5-Phosphate

49
Q

What enzyme is required for the addition of sulfates during proteogylcan synthesis?

A

Sulfotransferase

50
Q

What is TFPI?

A

Tissue Factor Pathway Inhibitor
aka
Anti-thrombin III

51
Q

What is the main source of TFPI?

A

Endothelial cells

52
Q

When is TFPI activated?

A

When limited quantities of factor Xa are generated

53
Q

How does TFPI exhibit its effect?

A

TFPI first binds to factor Xa, and then to tissue factor VIIa, thus forming an inactive quaternary complex.

54
Q

What induces the release of cell surface associated TFPI?

A

Heparin

55
Q

What does hyarluronic acid protect during ocular surgery?

A

Corneal endothelium

56
Q

How is hyaluronic acid used to treat patients with Osteoarthritis?

A

Intra-articluar injects = pallative effect

57
Q

How is hyaluronic acid useful postoperatively?

A

wound healing

anti-adhesive

58
Q

What can a defect in sulfation of GAGs lead to?

A

Chondodystrophy

59
Q

What is Chondodystrophy?

A

Disorder of the development and maintenance of the skeletal system

60
Q

Which GAG permits cell migration in the ECM?

A

hyaluronic acid in the ECM

61
Q

Describe glycoproteins

A

Mainly protein with some, often branched, sugars attached in O- or N-glycosylation. The amounts of carbohydrate is however very variable.

62
Q

What do glycoproteins function as?

A

Cell surface receptors
Blood group determinants
Collagen, Fibronectin
Protective Barrier

63
Q
  1. Are the sugars in blood group proteins linked in O-linkage or are they linked in N-linkage?
A

linked via O-linkage to proteins at their serine or threonine residues

64
Q

Is albumin a glycoprotein?

A

No, it is the exception

most other plasma proteins are glycoproteins

65
Q

What are mucins?

A

Large glycoproteins with negatively charged sialic acid

66
Q

What are other names for Salic Acid?

A

N-acetyl neuraminic acid

NANA

67
Q

What are the functions of mucins?

A
  • Trap water

- Serve as protective barriers

68
Q

What is the structure of mucins?

A

They have a long protein core and contain often negatively charged NANA
(N-acetylneuraminic acid or sialic acid) linked to single amino sugars

69
Q

What is the structure of Glycoproteins?

A

Oligosaccharide part (mixture of D-hexoses, NANA) + L-fucose (6-deoxy-L-galactose) (C6 has a methyl group)

70
Q

How are the oligosaccharides of glycoproteins attached to the protein?

A

N-glycosidic link

O-glycosidic link

71
Q

What amino acid makes up N-glycosidic link?

A

Asparagine

72
Q

What amino acids make up O-glycosidic link?

A

-OH group of Serine or Threonine

73
Q

What is the concept of O-glycosylation?

A

O-glycosylation is performed in the RER/Golgi and includes step by step linkage of activated sugars in an individual way.

74
Q

What is the concept of N-glycosylation?

A

N-glycosylation does not individually link sugars directly to the protein chain. Instead it uses a lipid bound in the ER membrane to form a precursor with several sugars that will be given in one step to proteins that are N-glycosylated

75
Q

What are two broad classes of N-linked Oligosaccharides?

A
  • Complex

- High Mannose

76
Q

What makes up complex N-linked oligosaccharides?

A

Diverse group of additional sugars:

  • N-acetylglucosamine (GlcNAc)
  • L-frucose (Fuc)
  • NANA
77
Q

To what region of Asparagine (Asn) are N-linked oligosaccharides attached?

A

Amide Nitrogen

78
Q

Glycosylation of O-linked glycoproteins occur where?

A

Golgi

79
Q

What is the main difference between N-linked glycosylation and O-linked glycosylation of glycoprotein synthesis?

A

N-linked glycoside biosynthesis uses lipid (dolichol) and phosphorylated lipid (dolichol phosphate)

80
Q

What’s special about the activated form of mannose in N-glycosylated glycoproteins?

A

Activated mannose is GDP-mannose, most other sugars are activated using UTP leading to UDP-sugars

81
Q

Regarding the biosynthesis of N-linked glycosides, what is the first step?

A

Protein in synthesized int he rER and enters lumen

82
Q

Regarding the biosynthesis of N-linked glycosides, what happens once the synthesized protein enters the lumen?

A

A lipid-linked oligosaccharide is constructed with dolichol

83
Q

Regarding the biosynthesis of N-linked glycosides, how is dolichol attached?

A

Through pyrophosphate linkage to oligosaccharide with N-acetylglucosamine, mannose and glucose

84
Q

Regarding the biosynthesis of N-linked glycosides, how are sugars added to dolichol?

A

By membrane bound glycosyltransferases

first N-acetylglucosamine, then mannose then glucose

85
Q

Regarding the biosynthesis of N-linked glycosides, how is the oligosaccharide transferred to protein?

A

Protein-oligosaccharide transferase present in ER

86
Q

Regarding the biosynthesis of N-linked glycosides, what happens after the N-linked Oligosaccharide is linked to the protein via Asn?

A

Processed by removal of specific mannosyl and glucosyl residues as glycoprotein moves through ER

87
Q

Regarding the biosynthesis of N-linked glycosides, where are oligosaccharide chains completed?

A

Golgi

88
Q

Regarding the biosynthesis of N-linked glycosides, how is it finally processed?

A

O-linked

89
Q

N-linked glycoproteins targeted to lysosomes are typically what?

A 
Hydrolytic enzymes such as:
Proteases
Lipases
Glucosidases
Nucleases
90
Q

What is I-cell disease?

A

Rare syndrome in which hydrolytic enzymes normally found lysosomes are absent.

91
Q

Individuals with I-cell disease lack what ability?

A

Enzymatic ability to phosphorylate mannose residues

92
Q

Are the enzymes needed for lysosomes made in patients with I-cell disease?

A

Yes, enzymes made but translocation ability deficient

enzyme ends up in plasma

Medical Biochemistry (35 decks)

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