(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
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
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
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-
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
Enzyme Defect
-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
-L-iduronidase
-L-iduronidase
L-iduronate-2-sulfatase
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
galactose-6-sulfatase
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
dermatan sulfate
-glucuronidase