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Medical Biochemistry > GAGs and glycoproteins > Flashcards

GAGs and glycoproteins Flashcards

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USMLE® Step 1 flashcards
1
Q

Other names for GAGs

A

Glycosaminoglycans, mucopolysaccharides, proteoglycans (I think that has a slightly more specific meaning but it doens’t matter for us so use it interchangably)

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2
Q

Basic properties of GAGs

A

repeating disaccharide units (amino sugar, acid sugar)
gel-like matrix, H2O binding, form ground substance, lubricating, stabilize and support cellular and fibrous components of tissue, maintain H2O and salt balance

stong negative charges, hydrated shell, compressible

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3
Q

Fxns of GAGs

A

cell shape maintenance, adhesion, migration, cell-cell communication, source of growth factors

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4
Q

Sugars in GAGs

A

Amino: D-glucosamine or D-Galactosamine
Acidic: D-glucuronic acid or L-iduronic acid
Keratan sulfate uses galactose

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5
Q

Major GAGs

A

Hyaluron (ic acid), Chondroitin sulfate, Keratan sulfate, Heparin, Heparan sulfate

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6
Q

Hyaluron

A

Hyaluronic acid, HA

No sulfates, not covalently linked to proteins

synovial fluid, vitreous humor, loose CT

large polymers, shock absorbing

D-glucuronic acid, N-Ac-D-glucosamine

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7
Q

Chondroitin sulfate

A

Most abundant GAG

cartilage, bone, heart valves

D-glucuronic acid, N-Acetyl-D-galactosamine (sulfated)

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8
Q

Keratan sulfate

A

aggregated with chondroitin sulfates

cornea, bone, cartilage

D-galactose, N-acetyl-D-glucosamine (sulfated)

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9
Q

Dermatan sulfate

A

Found in skin, blood vessels, heart valves

L-iduronic acid (sulfated), N-Ac-D-galactosamine (sulfated)

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10
Q

Heparin

A

component of intracellular granules in Mast cells lining arteries of lungs, liver and skin

More sulfated than heparan sulfates

D-Glucuronic or L-Iduronic acid (sulfated), N-Acetyl or N-sulfo-DGlucosamine

Anti-coagulent: Induces release of cell surface-associated TFPI (tissue factor pathyway inhibitor, anti-thrombin III)

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11
Q

Heparan sulfate

A

higher acetylated glucosamine than heparin

basement membranes, component of cell surfaces

D-Glucuronic or L-Iduronic acid (sulfated), N-Acetyl or N-sulfo-DGlucosamine

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12
Q

Strucutre of proteoglycans

A

attached to proteins (excpet HA) covallently attaced to protein to form proteoglycan monomers

≥100 monosaccharides

bottle brush

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13
Q

proteoglycan aggregates

A

chondroitin and keratin sulfates (i.e.: in cartilage) attached to protein core bound nonvovalently to HA (link proteins)

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14
Q

Linking sugars of proteoglycans

A

Gal-Gal-Xyl usually bound to Ser (Thr most likely alternative)

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15
Q

Steps of proteoglycan synthesis

A

synthesis of: amino sugars, acidic sugars, core protein, carbohydrate chain; addition of sulfate groups

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16
Q

Addition of sufate groups

A

ATP-sulfurase: ATP + SO42- –>Adenosine 5;-phosphosulfate (APS) + PPi
APS-kinase: APS + ATP –> 3’-phosphoadenoside 5’-phosphosulfate (PAPS) + ADP

Sulfotransferase: PAPS + sugar –> sulfated sugar + adenosine-5’, 3’-bisphosposphate

17
Q

Locations for proteoglycan synthesis

A

protein: cytosol/rER
Linker sugars added: ER (UDP-xyl, then 2x UDP-Gal)
Everything else: Golgi

18
Q

Warfarin

A

Vitamin K analog, anti-coagulent. Inhibits modification of several coagulation factors

slower acting than heparin, usually adminstered after

19
Q

TFPI

A

tissue factor pathway inhibitor, anti-thrombin III

binds factor Xa and VIIa forming inactive quaternary complex

20
Q

Applications of HA

A

used as lubricant to protect corneal endothelium in ocular surgery, god for patients with osteoarthritis (OA), anti-adhesive may be good for postsurgical wound healing

21
Q

Functions of glycoproteins

A

membrane bound: 1. cell surface recognition; 2. cell surface antigenicity; 3. componets of ECM; 4. contribute to glycocalyx and cellular protection

secreted glycoproteins: part of ECM, lubricants

intracellular: lysosomal enzymes

22
Q

Glycoprotein definition

A

protein with short oligosaccharide chain (2-10 residues), may or may not be branched or negatively charged

23
Q

Glycoproteins and cellular infections

A

E. coli –> adhere to mannose residues on plasma membrane of human cheek cells

H. pylori –> interact with blood group antigen on gastric endothelium (ulcers)

24
Q

Blood types

A

O-linked surgars (H substance) to protein (band 3?) or ceramide

25
Q

Mucins

A

Large, negatively charged, NANA (N-acetyl neuraminic acid), trap H2O, protective barriers

26
Q

N-Linked oligosaccharides

A

linked to amino group of Asn

Complex: N-acetylglucosamine (GlcNAc), L-Fucose (Fuc) and NANA

High mannose: mostly just mannose

27
Q

O-linked oligosaccharides

A

linked to Ser or The (Hyl in collagen)
often GalNAc
collagen has glucose-galactose dimer

28
Q

Synthesis of Glycoproteins: prep of sugars

A

Glucoseamine–>uses UDP-glucosamine
NANA–>uses CMP-NANA
Amine groups come from Gln

29
Q

Synthesis of O-linked glycoproteins

A

protein synthesized in rER

glycosylation in golgi, use specific

glycosyltransferases, add sugars sequentially
begins with transfer of GlcNAc (from UDP-GlcNAc) to Ser or Thr

intracellular are free within golgi, for cell membrane become part of golgi membrane with carb on outside

30
Q

Synthesis of N-linked glycoproteins

A
  1. protein synthesized in rER

2 & 3. ER: oligosaccharide constructed onto dolichol through pyrophosphate linkage (use membrane bound glycosyltransferases, 1)GlcNAc 2)Man 3)glu

  1. oligosaccharide transfered by protein-oligosaccharide tranferase in ER (to Asn)
  2. processed by removal of specific mannosyl and glucosyl resudues (ER)

6-7. Final processing in golgi: complex-add other sugars; final processing like O-linked

31
Q

Degredation of GAGs and Glycoproteins

A

Occurs in lysosomes following endocytosis

32
Q

Mucopolysaccaridosis

A

inability to degrade GAGs or glycoproteins

33
Q

Shingolipidosis

A

inability to degrade sphingolipids

34
Q

Enzyme transport to lysosomes

A

lysosomal enzymes tagged with N-linked mannose 6 phosphate

inability to tag leads to I-cell disease

Medical Biochemistry (24 decks)

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