GAG's & Glycoproteins

Question 1

Dermatan Sulfate

Answer 1

IdUA:
Iduronic Acid

GalNAC:
N-acetylgalactosamine

B-1,3

Sulfation? Yes

Mostly in skin, blood vessels, heart valves

Hunter/Hurler
Sanfilippo
Sly

Question 2

Keratan Sulfate I & II

Answer 2

Gal:
Galactose

GlcNAC:
N-acetylglucosamine

B-1,4

Sulfation? Yes

KS I: mainly in cornea
KS II: mainly in connective tissues

Morquio Syndrome A + B

Question 3

Heparin

Answer 3

IdUA:
Iduronic Acid

GlcN:
Glucosamine

a-1,4

Sulfation? Yes

Heparin: anticoagulant
- Intracellular - mast cells lining arteries, especially liver, lungs, skin

Question 4

Heparin Sulfate

Answer 4

GlcUA:
Glucuronic Acid

GlcNAC:
N-acetylglucosamine

a-1,4

Sulfation? Yes

HepS: membranes + cell surfaces

Hunter/Hurler
Sanfilippo
Sly

Question 5

Hyaluronic Acid

Answer 5

GLcUA:
Glucuronic Acid

GlcNAC:
N-acetylglucosamine

B-1,3

Sulfation? NO

Lubricant, shock absorber, synovial fluid (joints), vitreous humor of eye, umblical cord, loose CT + cartilage

Question 6

Chondroitin 4-Sulfate; Chondroitin 6-Sulfate

Answer 6

GlcUA:
Glucuronic Acid

GalNAC:
N-acetylgalactosamine

B-1,3

Sulfation? Yes

Cartilage (binds collagen)

Question 7

O-linked Glycoprotein Synthesis

Answer 7

• First: proteins to which oligosaccharides are to be attached are synthesized in the RER –> extruded into RER lumen –> transported to the Golgi
  
  • Glycosylation begins with transfer of N-acetyl galactosamine (GalNAc) from UDP-GalNAc onto R group of Serine or Threonine residue of the core protein in the Golgi
    ○ GalNAC-transferases are located in the Golgi
  • Oligosaccharide chain extension involves specific Glycosyltransferases:
    ○ Glycosyltransferases are bound to the Golgi

RBC Antigens

Question 8

N-linked Glycoprotein Synthesis

Answer 8

1. Protein synthesis begins and the polypeptide chain is extruded into the RER
   
   2. Branched oligosaccharide is synthesized on Dolichol Pyrophosphate
      a. Dolichol PP binds the oligosaccharide to inner ER wall
   3. Oligosaccharide is transferred from Dolichol to amide N of an Asparagine residue of the growing polypeptide chain
   4. Trimming of the carbohydrate chain begins as the protein moves through the RER
      a. Then the protein-carb complex is moved to the Golgi Apparatus
   5. In the Golgi: further trimming and/or addition of monosaccharides occurs –> complex glycoprotein
      - Vesicles bud off from the Golgi and their contents are targeted to:
      ○ The cell membrane
      ○ Extracellular environment
      ○ LYSOSOMES

Question 9

Transport of N-linked Glycoproteins to Lysosomes

Answer 9

• Acid hydrolases are targeted for lysosome residency by a Golgi bound Phosphotransferase
  ○ Phosphotransferase: (P)’s mannose residues (mannose-6-phosphate) of N-linked oligosaccharide of the hydrolase protein
  
  • Now the (P)-Mannose attaches to Mannose 6-P Receptor on the inner leaflet of lysosome vesicle + stays anchored*