GlycoBio: Proteoglycans/GAGs

Question 1

Proteoglycans (general)

Answer 1

Major component of the ECM

Also found on the surface of cells

Consist of a core protein with 1+ covalently attached glycosaminoglycans (GAGs)

Question 2

Condroitin sulfate-proteoglycan

Answer 2

Also referred to as Aggrecan

Most important proteoglycan in ECM

Components:

1. Core protein
2. ~100 chondroitin sulfate GAGs
3. ~30-50 keratan sulfate GAGs

Question 3

What consensus sequence does each GAG attach to on the core protein?

Answer 3

Serine-xylose-Gal-Gal

Question 4

In the presence of link protein,

Aggrecans can attach to ???

Answer 4

Hyaluronic acid

…to form an aggregate

Many aggrecans can attach to 1 HA

Question 5

Glycosaminoglycans (GAGs)

Answer 5

‘Mucopolysaccharides’

Long un-branched heteropolysaccs

Generally composed of a repeating disaccharide unit (hexose + hexosamine)

I.e. repeating unit = [acidic sugar-amino sugar]

All EXCEPT HA…attach to core proteins to form proteoglycans

Question 6

Types of GAGs

Answer 6

1. HA
2. Chondroitin sulfates (CSs)
3. Dermatan sulfate (DS)
4. Keratan sulfate (KS)
5. Heparin
6. Heparan sulfate (HS)

Question 7

Structure of Hyaluronic acid (HA)

Answer 7

Repeat: GlcA + GlcNAc

GlcA links to GlcNAc via beta-1,3

GlcNAc links to next GlcA via beta-1,4

LOCATIONS:

Vitreous humor in eye, synovial fluid in joints, and loose CT

Question 8

Chondroitin-4-sulfate

Or …6-sulfate

Answer 8

REPEAT: GlcA + GalNAc**

**difference from HA

C4/6 of GalNAc = sulfated (look at name)

Beta-1,3 …. then beta-1,4 linkages

LOCATION: cartilage, tendons, and ligaments

Question 9

Dermatan sulfate (DS)

Answer 9

REPEAT: L-IdoA** + GalNAc4S

**difference from CS

LINKAGES: alpha-1,3….beta-1,4

C2 of L-IdoA is usually sulfated

C4 of GalNAc is usually sulfated

LOCATION:

Skin, blood vessels, and heart valves

Question 10

Keratan sulfate (KS)

Answer 10

Repeat: Gal + GlcNAc
(N-acetyllactosamine)

LINKAGES: beta-1,4….beta-1,3

C6 of both usually sulfated***

How can tell the repeat from regular lactose

LOCATION:

Cartilage and cornea

Question 11

Heparin (HP) & Heparan sulfate (HS)

Answer 11

HP = intracellular component of mast cells (liver, lung, and vessel wall)

HS = extracellular component of cell surfaces

REPEAT (both same):

(L-IdoA or D-GlcA) + (D-GlcN)

LINKAGES:

L-IdoA + D-GlcN = alpha-1,4

D-GlcA + D-GlcN = beta-1,4

D-GlcN + ‘either’ = alpha-1,4

**Note: all linkages are 1,4 —> unique amongst GAGs

BOTH:

C2 of I-IdoA = sulfated (like DS)

C3/C6 GlcN OH groups = sulfated

GlcN Amino groups (in HP) = most N-sulfated/acetylated

General:

HP contains more L-IdoA and more N/O-sulfated GlcN

Question 12

Clinical use for Heparin (HP)

Answer 12

Anticoagulant

HP binds to and activates antithrombin III —> thrombin inactivation

Antithrombin binds to specific 5 sugar sequence found in both HP and HS

Question 13

The 3 GAGs associated with mucopolysaccharidosis

Answer 13

DS

HS

KS