CLINICAL CASES
265
Glycosaminoglycan (GAG): Formerly known as mucopolysaccharide;
a heteropolysaccharide composed of a repeating disaccharide of an
N-acetylated hexosamine (glucosamine or galactosamine) and an acidic
hexose (glucuronic acid or iduronic acid); this repeating disaccharide
unit is frequently sulfated in one or more positions; most glycosamino-
glycans are covalently linked to a core protein in structures known as
proteoglycans.
Hyaluronan: Formerly known as hyaluronic acid; a glycosaminoglycan
composed
of
alternating
residues
of glucuronic
acid
and
N-
acetylglucosamine. Hyaluronan is not sulfated nor is it covalently linked
to a protein.
Mucopolysaccharidosis: A genetic disorder involving a lack of a lysoso-
mal enzyme required for the degradation of glycosaminoglycans leading
to buildup of glycosaminoglycans in the lysosome and increased excre-
tion of glycosaminoglycan fragments in urine.
Sulfatase: An enzyme that catalyzes the hydrolysis of sulfate ester bond
releasing free inorganic sulfate from the substrate.
D ISC U SSIO N
The extracellular matrix that surrounds and binds certain types of cells is com-
posed of a number of components including fibrous structural proteins such as
various collagens, adhesive proteins like laminin and fibronectin, and proteo-
glycans that form the gel into which the fibrous structural proteins are embed-
ded. Proteoglycans are very large macromolecules consisting of a core protein
to which many long polysaccharide chains called glycosaminoglycans are
covalently bound. Due to the high negative charge of the glycosaminoglycans,
the proteoglycans are very highly hydrated, a property that allows the proteo-
glycans to form a gel-like matrix that can expand and contract. The proteo-
glycans are also effective lubricants.
The glycosaminoglycans (GAGs, formerly called mucopolysaccharides) are
long, linear polymers of repeating disaccharide units containing an acidic sugar
(glucuronic acid or iduronic acid) and a hexosamine (glucosamine or galac-
tosamine, both usually N-acetylated). The exception to this general structure is
keratan sulfate, which has galactose in place of the acidic hexose. Table 29-1
lists the various types of GAGs and the structures of their repeating disaccha-
ride units. The GAGs are often highly sulfated, which increases their negative
charge and their ability to bind water molecules. All of the GAGs except
hyaluronan are covalently linked to one of approximately 30 different core
proteins to form proteoglycans. The core protein is synthesized on the rough
endoplasmic reticulum and transferred to the Golgi where nucleoside
diphosphate-activated acidic and amino sugars are alternately added to the
nonreducing end of the growing polysaccharide by glycosyltransferases,
resulting in the characteristic repeating disaccharide structure common to the
GAGs. Hyaluronan, which is not sulfated nor covalently linked to a core protein,
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