A Long unbranched polysaccharide A heterosaccharide sulfate group or carboxyl group.

(Campbell,2006) they are highly negative with extended conformation that imparts high viscosity to the solution their rigidity provides structural integrity to cells and provides passageways between cells, allowing for cell migration.

 N-acetylgalactosamine(GalNAc)

or N-acetylglucosamine(GlcNAc)
is an amino sugar derivative of galactose.

 Uronic acid: glucuronate or iduronate is a sugar acid with both a carbonyl and a carboxylic acid function

The majority of GAGs in the body are linked to core proteins, forming proteoglycans (mucopolysaccharides) The GAGs extend perpendicularly from the core in a brush-like structure. The linkage of GAGs to the protein core involves a specific trisaccharide composed of two galactose residues and a xylose residue (GAG-GalGalXyl-O-CH2-protein).

glycoproteins that are heavily glycosylated core protein with one or more covalently attached (GAG) chain(s). long, linear carbohydrate polymers that are negatively charged under physiological conditions,
 sulfate and uronic acid groups.  occur in the connective tissue

large proteoglycans are

 aggrecan the major proteoglycan in cartilage  versican present in many adult tissues including blood vessels and skin.

The small leucine-rich repeat proteoglycans (SLRPs) include decorin, biglycan, fibromodulin and lumican.

HEPARIN HEPARAN SULFATE HYALURONATE CHONDROITIN SULFATE DERMATAN SULFATES KERATAN SULFATES

 a highly-sulfated

glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule  Heparin is a naturallyoccurring anticoagulant produced by basophils and mast cells.

a linear polysaccharide found in all animal tissues. Basement membranes developmental processes, angiogenesis, blood coagulation and tumour metastasis. cellular receptor for viruses including the respiratory syncytial virus (Hallak et al. 2000)

an anionic, non-sulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues increase the viscosity Shock absorbent Tissue repair tissue hydrodynamics, movement and proliferation of cells, cell surface receptor interactions

composed of a chain of alternating sugars (Nacetylgalactosamine and glucuronic acid). A chondroitin chain can have over 100 individual sugars, each of which can be sulfated in variable positions and quantities

Chondroitin sulfate is an important structural component of cartilage and provides much of its resistance to compression As part of aggrecan,  a major component of cartilage electrostatic repulsion  resistance of cartilage to compression cause of osteoarthritis

mostly in skin, but also in blood vessels, heart valves, tendons, and lungs. coagulation Dermatan sulfate may have roles in coagulation, cardiovascular disease, carcinogenesis, infection, wound repair, and fibrosis.

found especially in the cornea, cartilage, and bone It is also synthesized in the central nervous system where it participates both in development and in the glial scar formation following an injury. large, highly hydrated molecules which in joints can act as a cushion to absorb mechanical shock

GAG
Hyaluronate Chondroitin sulfate Heparan sulfate

Localization
synovial fluid, vitreous humor, ECM of loose connective tissue cartilage, bone, heart valves basement membranes, components of cell surfaces component of intracellular granules of mast cells lining the arteries of the lungs, liver and skin skin, blood vessels, heart valves cornea, bone, cartilage aggregated with chondroitin sulfates

Comments
large polymers, shock absorbing most abundant GAG contains higher acetylated glucosamine than heparin more sulfated than heparan sulfates

Heparin

Dermatan sulfate

Keratan sulfate

are a group of metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down molecules called glycosaminoglycans - long chains of sugar carbohydrates in each of our cells that help build bone, cartilage, tendons, corneas, skin and connective tissue.

Hurler Scheie Hurler- Scheie Hunter Sanfilippo A/B/C/D Morquio A/B Maroteaux-Lamy Sly

Enzyme defect: -L-iduronidase Affected GAG: dermatan sulfate, heparan sulfate

corneal clouding dystosis multiplex Organomegaly heart disease dwarfism mental retardation early mortality

 s/s:

 Enzyme defect : -L-iduronidase  Affected GAG: dermatan sulfate, heparan sulfate  s/s: corneal clouding; aortic valve disease; joint stiffening; normal intelligence and life span

Enzyme defect: -L-iduronidase Affected GAG: dermatan sulfate, heparan sulfate s/s:
 intermediate between I H and I S

Enzyme defect: L-iduronate-2-sulfatase Affected GAG: dermatan sulfate, heparan sulfate s/s:

    

mild and severe forms only X-linked MPS dystosis multiplex organomegaly facial and physical deformities no corneal clouding mental retardation death before 15 except in mild form then survival to 20 - 60

Sanfilippo A
 Enzyme defect: heparan N-sulfatase  Affected GAG: heparan sulfate  s/s:  profound mental deterioration  Hyperactivity  skin, brain, lungs, heart and skeletal muscle are

affected in all 4 types of MPS-III

Sanfilippo B
 Enzyme defect: -N-acetyl-D-glucosaminidase  affected GAG: heparan sulfate  s/s: phenotype similar to III A

Sanfilippo C
 enzyme defect: acetylCoA: -glucosaminide-

acetyltransferase  affected GAG: heparan sulfate  s/s:

phenotype similar to III A

Sanfilippo D
 enzyme defect: N-acetylglucosamine-6-sulfatase  Affected GAG: heparan sulfate  s/s: phenotype similar to III A

Morquio A
 enzyme defect: galactose-6-sulfatase  Affected GAG: keratan sulfate, chondroitin 6-

sulfate  s/s:
corneal clouding, odontoid hypoplasia, aortic valve disease, distinctive skeletal abnormalities

Morquio B
 Enzyme defect: -galactosidase  Affected GAG : keratan sulfate  s/s: severity of disease similar to IV A

Enzyme defect: arylsulfatase B also called Nacetylgalactosamine-4-sulfatase Affected GAG: dermatan sulfate s/s:

     

3 distinct forms from mild to severe, aortic valve disease, dystosis multiplex, normal intelligence, corneal clouding, coarse facial features

Enzyme defect: -glucuronidase Affected GAG: heparan sulfate, dermatan sulfate, chondroitin 4-, 6-sulfates s/s:
 hepatosplenomegaly,  dystosis multiplex,  wide spectrum of severity,  hydrops fetalis

Type:Syndrome Hurler MPSIH (MPS1H)

Enzyme Defect

Affected GAG dermatan sulfate, heparan sulfate

-L-iduronidase

Symptoms corneal clouding, dystosis multiplex, organomegaly, heart disease, dwarfism, mental retardation; early mortality corneal clouding; aortic valve disease; joint stiffening; normal intelligence and life span intermediate between I H and I S mild and severe forms, only X-linked MPS, dystosis multiplex, organomegaly, facial and physical deformities, no corneal clouding, mental retardation, death before 15 except in mild form then survival to 20 - 60

Scheie MPSIS (MPS1S) Hurler-Scheie MPSIHS (MPS1HS)

-L-iduronidase

dermatan sulfate, heparan sulfate dermatan sulfate, heparan sulfate

-L-iduronidase

Hunter MPSII (MPS2)

L-iduronate-2-sulfatase

dermatan sulfate, heparan sulfate

MPS VIII, a designation no longer used

Sanfilippo A heparan N-sulfatase MPSIIIA (MPS3A)

heparan sulfate

Sanfilippo B MPSIIIB (MPS3B) Sanfilippo MPSIII (MPS3 ) Sanfilippo D MPSIIID (MPS3D)

-N-acetyl-Dglucosaminidase acetyl oA: glucosaminideacetyltransferase Nacetylglucosamine6-sulfatase

heparan sulfate heparan sulfate

profound mental deterioration, hyperactivity, skin, brain, lungs, heart and skeletal muscle are affected in all 4 types of MPS-III phenotype similar to III A phenotype similar to III A phenotype similar to III A

heparan sulfate

Morquio A MPSIVA (MPS4A)

galactose-6-sulfatase

keratan sulfate, chondroitin 6-sulfate

Morquio B -galactosidase MPSIVB (MPS4B) MPS V, a designation no longer used arylsulfatase Balso called Nacetylgalactosamine-4sulfatase

keratan sulfate

corneal clouding, odontoid hypoplasia, aortic valve disease, distinctive skeletal abnormalities severity of disease similar to IV A 3 distinct forms from mild to severe, aortic valve disease, dystosis multiplex, normal intelligence, corneal clouding, coarse facial features hepatosplenomegaly, dystosis multiplex, wide spectrum of severity, hydrops fetalis

Maroteaux-Lamy MPSVI (MPS6)

dermatan sulfate

Sly MPSVII (MPS7)

-glucuronidase

heparan sulfate, dermatan sulfate, chondroitin 4-, 6sulfates