Proteoglycans

-ECM
-form the hydrated polysaccharide gel that acts as a ground substance and allows diffusion of
substances such as nutrients and hormones, from the blood to tissue and vice versa. It is consist of a
core protein molecule to which chains of glycosaminoglycans (GAGs) are covalently attached.

 Glycosaminoglycans (GAGs)
- are unbranched polysaccharide chains of repeating disaccharide units (A-B-A-B where A and
B represent two different sugars)
repeating disaccharide consists of: 1.Amino sugar - N-Acetylglucosamine or N-
Acetylgalactosamine 2. Acidic sugar- Hyaluronic acid or Glucoronic acid
- Highly acidic- due to the presence of both sulfate and carboxyl group attached to the sugar
rings
- Very hydrophilic
- Has an extended coil structure which takes up extensive pace
- Polyanions: have a lot of negative charges because of huge number of carboxylic and sulfate
groups which attract polycations (Na+, K) bringing water into the matrix giving turgor
pressure able to withstand forces of many hundreds of times atm pressure

Proteoglycans function to:

-provide hydrated space: It binds huge number of cations which in turn bind large number of water
molecules which results to form a porous, hydrated gel that fills the extracellular space like packing
material that resists crushing (compression forces)
-bind secreted signaling molecules: a number of growth factors have been found to bind to
proteoglycans including fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF)
-act as sieves to regulate molecular trafficking: polyanions interact with polycations which traps water;
they act as molecular sieves that trap small molecules and does not allow these molecules to move from
one place to another place

Proteoglycans are formed in the Golgi apparatus where:

 the core protein is linked via a serine to a tetrasachharide

 glycosyl transferases add sugar residues
 ordered sulphation and epimerization reactions (conversion of some amino acids from their
natural L-isomer to the D-isomer) occur

Formed through:

1. O-type linkages

Ser- O- Xylose- gal-gal-repeating dissacharide (GAGs)

2. N-type linkages- synthesized in the Rough endoplasmic reticulum

Endoplasmic reticular membrane which has a lipid molecule, dolichal pyrophosphate with two
phosphates attached. To the dolichal pyrophosphate, olisaccharide unit will be attached and then
transferred to a protein molecule, asparagine. To its side chain nitrogen, the entire oligosachharide
chain are transferred. Further processing takes place in golgi complex.

Role of dolichal pyrophosphate: a lipid molecule with a phosphate attached to the RER and the
carbohydrate is built from it and added to nitrogen side of Asp

Main types of GAGs are:

1. Hyaluronic acid – has high negative charges and act as a lubricant in synovial fluid and shock absorber
in a joint; helps in cell migration during embryogenesis and morphogenesis and also in wound healing
process; Atherosclerosis

2. Chondroitin sulfate- found in ECM especially in cartilage which is involved in bone and cartilage
formation; hold tightly to ECM which make cartilage and bone

3. Dermatan sulfate- found in skin, heart, blood vessel and transparency of cornea

4. Heparin sulfate- found in the basement membrane; helps in the formation of stratified squamous
epthelium; important in glomerular filtration. Glomerulus has charge selectiveness and filters based on
the size and the charge because of the presence of heparin sulfate which are highly negative charge.
Heparin sulfate are present on basement membranes of kidney.

5. Heparin- only intracellular GAGs; acts as anticoagulant

6. Keratin sulfate- found in skin

Two types:

a) Keratin sulfate I- found in cornea; systematic arrangement resulting to the transparency of

cornea

b) Keratin sulfate II- found in loose connective tissue

Four leucine rich repeat proteoglycans are present in the extracellular matrix of corneal stroma:
1. decorin 2. lumican 3. mimecan and 4. keratocan
 The first is a dermatan sulfate proteoglycan and the last three are keratan sulfate
proteoglycan
 Dermatan sulfate proteoglycan- are involved in the regulation of collagen fibril diameter