10 Glycosaminoglycans, Proteoglycans, and Glycoproteins

Glycosaminoglycans (GAGs)

Large complexes of negatively charged heteropolysaccharides.

Proteoglycans

Formed by GAGs associated with a small amount of core protein.

Water

Large amounts are bound by GAGs

Extracellular matrix components

Contains collagen

Basic structure of GAGs

A repeating acidic sugar-amino sugar polymer.

Keratan sulfate

The only GAG that contains galactose instead of an acidic sugar.

Amino sugars in GAGs

D-glucosamine and D-galactosamine.

Amino sugars

Usually acetylated in GAGs.

Sulfation of amino sugars

May occur at carbon C-4 or C-6.

Acidic sugar in GAGs

Can be D-glucuronic acid or its epimer L-iduronic acid.

Strongly negative charge of GAGs

Comes from carboxyl and sulfate groups.

GAG chains

Repel each other due to their charge.

Shell of water

GAGs are surrounded by a shell of water.

Slippery nature of mucous secretions

Due to GAGs.

Resilience of GAGs

Allows them to return to their original hydrated volume when compressed.

Chondroitin sulfate

The most abundant GAG in cartilage.

Hyaluronic acid

Unique because it has no sulfate and is not protein-bound.

Hyaluronic acid in bacteria

Also found in bacteria.

Chondroitin sulfate sugars

Contains N-acetylgalactosamine and glucuronic acid.

Dermatan sulfate

Found in skin and blood vessels.

Acidic sugar in dermatan sulfate

L-iduronic acid.

Heparan sulfate

Found in basement membranes.

Heparin

Synthesized and stored in mast cells.

Highly sulfated GAG

Heparin

Keratan sulfate uniqueness

Contains galactose instead of uronic acid.

Keratan sulfate locations

Found in the cornea and cartilage.

Hyaluronic acid injections

Used as dermal fillers.

High molecular weight hyaluronic acid

Remains on the surface and provides surface hydration.

Low molecular weight hyaluronic acid

Penetrates deeper and improves plumping and elasticity.

Cross-linked hyaluronic acid

Used as injectable dermal fillers.

Proteoglycan

A molecule consisting of a protein core with covalently attached GAG chains.

Compression

A force that proteoglycans can resist.

Glycoproteins

Molecules that contain protein plus short

Sugar content comparison

The sugar content of glycoproteins is less than that of proteoglycans.

Cell recognition

One of the important functions of glycoproteins.

Signaling

Another important function of glycoproteins.

ABO blood group antigens

Glycoproteins are part of these antigens.

Blood group A

Has a terminal GalNAc sugar.

Blood group B

Has a terminal Galactose sugar.

Blood group O

Has neither GalNAc nor galactose terminal sugar.

Unbranched

The type of chains of disaccharide units found in proteoglycans.

Branched

The type of sugar chains found in glycoproteins with no repeating units.

GAGs

Molecules characterized by a repeating disaccharide structure.

ECM

A location where GAGs are mainly found.

Cartilage

Another location where GAGs are mainly found.

Membranes

One of the main locations for glycoproteins.

Secretions

Another main location for glycoproteins.

Structure

One of the functions provided by GAGs to tissues.

Hydration

Another function provided by GAGs to tissues.

Cushioning

One of the functions provided by proteoglycans.

Cell signaling

One of the functions of glycoproteins.

Recognition

Another function of glycoproteins.

Golgi

The organelle where GAGs are synthesized.

ER

One of the organelles where proteoglycans and glycoproteins are synthesized.

Lysosomes

The organelles where GAGs

Hurler syndrome

A condition caused by a deficiency in α-L-iduronidase.

Hunter syndrome

A condition caused by a deficiency in iduronate sulfatase.

X-linked

The inheritance pattern of Hunter syndrome.

Sly syndrome

A condition caused by a deficiency in β-glucuronidase.

Multiple GAGs

The substances that accumulate in Sly syndrome.

Sanfilippo syndrome

A condition caused by a deficiency in N-acetylglucosaminidase.

Tetrasaccharide

A linker added in GAG synthesis.

Xylosyltransferase

The enzyme that adds the linker tetrasaccharide.

Repeating disaccharide units

Added during GAG synthesis.

Glycosyl transferases

Add the repeating disaccharide units during GAG synthesis.

Sulfotransferases

Add sulfate groups using PAPS as a donor.

Fructose-6-phosphate

The precursor of GlcNAc and GalNAc.

Glutamine

The amine donor in amino sugar synthesis.

UDP-GlcNAc

An activated form of amino sugars.

UDP-GalNAc

An activated form of amino sugars.

N-acetylneuraminic acid (NANA)

The 9-carbon acidic monosaccharide in sialic acids.

CMP-NANA

The activated form of NANA in human metabolism.

C-5

L-iduronic acid is a C-5 epimer of D-glucuronic acid.

Uronosyl 5-epimerase

The enzyme that converts D-glucuronic acid to L-iduronic acid.

Lysosomal degradation of GAGs

One source of glucuronic acid.

D-xylulose 5-phosphate

The end-product of glucuronic acid metabolism.

5

The optimal pH for lysosomal hydrolases.

Asparagine

One of the amino acids sugars in glycoproteins can be added to (N-linked).

serine/threonine

One of the amino acids sugars in glycoproteins can be added to (O-linked).

Dolichol phosphate

N-linked sugars are first built on this in the ER.

Protein

N-linked oligosaccharides are transferred to this during protein synthesis.

Mucopolysaccharidoses (MPS)

Result from defective degradation of GAGs.

Very high

The sugar content of GAGs.

High

The sugar content of proteoglycans.

Low

The sugar content of glycoproteins.

Linear

The structure of GAGs.

Core protein with GAG chains

The structure of proteoglycans.

Branched sugars

The structure of glycoproteins.

Structural support

One of the functions of GAGs.

Elasticity

Hyaluronic acid contributes to tissue elasticity and repair.

Anticoagulant

Heparin is clinically important as this.

ABO

Glycoproteins are involved in immune recognition and blood group determination