GLYCOSAMINOGLYCANS, PROTEOGLYCANS, AND GLYCOPROTEINS Flashcards
long chains of sugar molecules that are found in the extracellular matrix (ECM) of all tissues throughout the body.
Glycosaminoglycans (GAGs)
Found in: cartilage, bone, skin, tendons, ligaments, blood vessels, synovial fluid, vitreous humor of the eye
GLYCOSAMINOGLYCANS
natural anticoagulant that helps to prevent blood clot
GAG heparin
are long, unbranched, heteropolysaccharide chains composed of a repeating disaccharide unit [acidic sugar–amino sugar]n
GAGs
[Acidic sugar can be either D-glucuronic acid or its C-5 epimer L-iduronic acid, and the amino sugar can be either ___
glucosamine or galactosamine.]
are strongly negative charged, due to the presence of carboxyl groups that the acidic sugars contain, and sulfate groups.
GAGs
6 TYPES GLYCOSAMINOGLYCANS
:
Hyaluronic acid (HA)
Chondroitin sulfate (CS)
Dermatan sulfate (DS)
Heparan sulfate (HS)
Heparin
Keratan sulfate (KS)
the only GAG that is not sulfated. It is composed of repeating disaccharide units of N-acetylglucosamine and D-glucuronic acid.
found in all tissues throughout the body, but it is particularly abundant in the synovial fluid of joints and the vitreous humor of the eye.
Hyaluronic acid (HA)
composed of repeating disaccharide units of Nacetylglucosamine and D-glucuronic acid or L-iduronic acid. (in cartilage, bone, skin, and other tissues throughout the body)
Chondroitin sulfate (CS)
is a type of CS that is distinguished by its high degree of sulfation. (found in skin, tendons, and other tissues.)
Dermatan sulfate (DS)
composed of repeating disaccharide units of Nsulfoglucosamine and D-glucuronic acid or L-iduronic acid. (found in the cell membrane and extracellular matrix of all tissues throughout the body.)
Heparan sulfate (HS
is a type of HS that is highly sulfated. (found in mast cells and basophils, and it plays a role in blood coagulation.)
Heparin
composed of repeating disaccharide units of galactose and N-acetylglucosamine. (found in the cornea, cartilage, and other tissues.)
Keratan sulfate (KS)
are the activated forms of the monosaccharides that can be used to elongate the carbohydrate chains
N-acetylglucosamine (GlcNAc)
N-acetylgalactosamine (GalNAc)
is synthesized from N-acetylmannosamine and phosphoenolpyruvate.
N-acetylneuraminic acid (NANA)
is the only nucleotide sugar in human metabolism in which the carrier nucleotide is a monophosphate.
NANA
: can be obtained from the a.) lysosomal degradation of GAGs, or from b.) glucose 6- phosphate via the uronic acid pathway.
Glucuronic acid
The end product of glucuronic acid metabolism in humans
D-xylulose 5- phosphate.
The source of the sulfate is _____. The sulfation reaction is catalyzed by sulfotransferases.
3’- phosphoadenosyl-5’-phosphosulfate (PAPS)
defect in the sulfation of the growing glycosaminoglycan chains where the proper development and maintenance
Chondrodystrophies
is a rare lysosomal storage disease in which all sulfatases are nonfunctional due to a defect in the formation of formylglycine, an amino acid derivative required at the active site for enzymic activity to occur
Multiple sulfatase deficiency
hereditary diseases caused by a deficiency of any one of the lysosomal hydrolases normally involved in the degradation of heparan sulfate and/or dermatan sulfate.
MUCOPOLYSACCHARIDOSES
α-L-iduronidase deficiency
most severe form of MPS
corneal clouding, developmental disability, dwarfing, coarse (dysmorphic) facial features, upper airway obstruction, hearing loss
degradation of dermatan sulfate and heparan sulfate affected
a.) Hurler Syndrome (MPS I H)
severe nervous system disorders; developmental disability
b.) San Filippo Syndrome Types A-D (MPS III)
Iduronate-sulfatase deficiency
no corneal clouding, but physical deformity and developmental disability are mild to severe
degradation of dermatan sulfate and heparan sulfate affected
c.) Hunter Syndrome (MPS II)
β-glucuronidase deficiency
hepatosplenomegaly, skeletal deformity, short stature, corneal clouding, developmental stability
degradation of dermatan sulfate and heparan sulfate affected
d.) Sly Syndrome (MPS VII)
are large molecules that are made up of a protein core and one or more GAG chains.
found in the extracellular matrix (ECM) of all tissues throughout the body.
PROTEOGLYCANS
are structured like a “bottle brush,” with the protein core at the center and the GAG chains extending out like bristles.
PROTEOGLYCANS
An ____ is formed between the xylose and the hydroxyl group of the serine.
O-glycosidic bond
are proteins with short chains of sugars (oligosaccharides) attached to them.
found all over the body, including on the surface of cells, in the blood, and in the extracellular matrix.
They differ from proteoglycans in that proteoglycans have very long chains of repeating sugars (GAGs).
Examples: hormones, enzymes, blood group antigens, mucin, collagen, elastin
GLYCOPROTEINS
are short chains of sugars that are attached to proteins to form glycoproteins.
Oligosaccharides
simple, with only a few sugar residues, or they can be quite complex, with many sugar residues and branching patterns.
For example, the ABO blood group antigens on the surface of red blood cells are determined by the structure of O-linked oligosaccharides.
O-linked oligosaccharides
more complex than O-linked oligosaccharides. They all contain a core pentasaccharide, which is a chain of five sugar residues.
N-linked oligosaccharides
the sugar chain is attached to the nitrogen atom of an asparagine amino acid
N-linked glycosylation
the sugar chain is attached to the oxygen atom of a serine or threonine amino acid residue.
O-linked glycosylation:
similar to that of the GAGs
if any one degradative enzyme is missing, degradation by the other exoenzymes cannot continue.
LYSOSOMAL DEGRADATION OF GLYCOPROTEINS
caused by a deficiency of any one of the degradative enzymes results in accumulation of partially degraded structures in the lysosomes
Oligosaccharidoses
