section ii.i
Protein Fibers and Proteoglycans
183
Hyaluronic Acid
CH,OH
io
[glucuronate-ß 1, 3-NacetyIgIucosamine-ß 1,4]-
NH
I
Ac
Os
Dermatan Sulfate
[iduronate-a 1 ,3 .
.
Ac
fglucuronate-ß I, 3-NacetyIgIucosamine-ß 1, 4]-
4 or 6 sulfate
Keratan Sulfate
-
0
.
OH(SO,©)
/
C H 2
^J-o
HO
NH
I
Àc
OH
oso©
/
3
? H2
C J -
o
[Nacetylglucosamine-ß 1, 3-galactose-ß 1,4]-
(or Ac)
-|glucuronate-ß 1,3-.
. .]-
-fiduronate-a 1, 4-Nsulfate glucosamine-a 1,4]-
I
(acetate)
J
2-sulfate
6-sulfate
FIGURE 11-7
Basic repeating disaccharide units of six classes of glycosaminoglycans.
Chondroitin sulfate and dermatan sulfate differ in type of principal uronic
acid residue; the former contains glucuronate and the latter iduronate.
Heparin and heparan sulfate differ in that heparin contains more iduronate
2-sulfate and N-sulfated glucosamine residues than heparan sulfate. In the
sulfate-containing glycosaminoglycans, the extent of sulfation is variable.
All of these molecules have a high negative charge density and are
extremely hydrophilic. [Reproduced with permission from V. C. Hascall
and J. H. Kimura; Proteoglycans: Isolation and characterization. In
M eth.
E n zym o l.
82(A), L. W. Cunningham and D. W. Frederiksen. Eds.
Academic Press, San Diego (1982).]
disaccharide units consist of amino sugars
(usually
D-galactosamine) alternating with uronic acids. In one
type, keratan sulfate, the uronic acid is replaced by galac-
tose. The amino sugars are usually present as N-acetyl
derivatives. In heparin and heparan sulfate, however, most
amino sugars are found as N-sulfates in sulfamide link-
age, with a small number of glucosamine residues as
N-acetyl derivatives. With the exception of hyaluronate,
all glycosaminoglycans contain sulfate groups in ester
linkages with the hydroxyl groups of the amino sugar
residues.
The presence of carboxylate and sulfate groups provides
the glycosaminoglycans with a high negative charge den-
sity and makes them extremely hydrophilic. Almost all
water in the intercellular matrix is bound to glycosamino-
glycans, which assume a random conformation in solu-
tion, occupying as much solvent space as is available by
entrapping the surrounding solvent molecules. In solu-
tion, glycosaminoglycans also undergo aggregation and
impart a high viscosity. In order to maintain electrical
neutrality, negatively charged (anionic) groups of gly-
cosaminoglycans, fixed to the matrix of the connective
tissue, are neutralized by positively charged (cationic)
groups (e.g., Na+). Osmotic pressure within the matrix
is thereby elevated, contributing turgor to the tissue. Thus,
proteoglycans, because they contain glycosaminoglycans,
are polyanionic and usually occupy large hydrodynamic
volumes relative to glycoproteins or globular proteins of
equivalent molecular mass. Usually, they have high buoy-
ant densities, and this property has been utilized in their
isolation and characterization. The physical properties of
connective tissue also depend on collagen or elastin fibers.
Collagen fibers resist stretching and provide shape and
tensile strength; the hydrated network of proteoglycans
resists compression and provides both swelling and pres-
sure to maintain volume (Figure 11-8). Thus, the proper-
ties of these different macromolecules are complemen-
tary, and their relative compositions vary according to
tissue function.
For example,
sulfated glycosamino-
glycans tend to provide a solid consistency, whereas
hyaluronate provides a softer, more fluid consistency. The
vitreous space behind the lens of the eye is filled with
a viscous, gelatinous solution of hyaluronate free of fi-
brous proteins and transparent to light. Hyaluronate is not
sulfated, and there is no evidence that it is linked to a
protein molecule, as are the other glycosaminoglycans.
Hyaluronate is also present in synovial fluid in joint cavi-
ties that unite long bones, bursae, and tendon sheaths. The
viscous and elastic properties of hyaluronate contribute to
the functioning of synovial fluid as a lubricant and shock
absorber.
Hyaluronate is depolymerized by hyaluronidase, which
hydrolyzes the /3(1 —»■
4) glycosidic linkages between
N-acetylglucosamine and glucuronate. Some pathogenic
bacteria secrete hyaluronidase, which breaks down the
protective barrier of hyaluronate and renders the tissue
more susceptible to infection. Hyaluronidase, found in
spermatozoa, may facilitate fertilization by hydrolyzing
the outer mucopolysaccharide layer of the ovum, thereby
enabling the sperm to penetrate it. Hyaluronidase (pre-
pared from mammalian testes) is used therapeutically to
enhance dispersion of drugs administrated in various parts
of the body.
