section
11.1
Protein Fibers and Proteoglycans
185
FIGURE 11-9
Schematic representation of cartilage proteoglycan. The monomers,
consisting of glycosaminoglycan chains linked to a core protein by
covalent linkage, extend laterally at intervals from opposite sides of a very
long filament of hyaluronate. The interaction between the core protein and
hyaluronate is noncovalent and is aided by the link protein. The entire
structure is highly hydrated and occupies a large volume. [Reproduced
with permission from W. J. Lennarz,
T he B io ch em istry o f G lyco p ro tein s
a n d P ro teo g lyca n s,
Plenum Press, New York, 1980].
their longitudinal growth ceases. Its smooth surface pro-
vides for freely movable joints (e.g., knee and elbow). The
properties of cartilage depend on its content of collagen
(or collagen and elastin) and proteoglycans. Cells respon-
sible for the synthesis and maintenance of cartilage are
known as
chondrocytes.
The proteoglycan monomer of cartilage consists of
glycosaminoglycan chains of chondroitin sulfate and
keratan
sulfate
covalently
linked to
a core protein
(Figure 11-9) about 300 nm long with molecular weight
of 250,000. Each molecule of core protein contains about
80 chondroitin sulfate and
1 0 0
keratan sulfate chains.
The linkage between the oligosaccharides and the pro-
tein can be O-glycosidic between xylose and serine
residues, O-glycosidic between N-acetylgalactosamine
and serine or threonine residues, or N-glycosidic between
N-acetylglucosamine and the amide nitrogen of as-
paragine. The glycosaminoglycan chains with their nega-
tively charged groups extend out of the core protein to
occupy a large volume and to entrap surrounding sol-
vent. One end of the core protein has relatively few or
no attached glycosaminoglycan chains and resembles a
glycoprotein; at this end, the core protein possesses an ac-
tive site that binds to a very long filament of hyaluronate
by a noncovalent interaction at intervals of 30 nm. The in-
teraction between the core protein and the hyaluronate is
aided by a protein (M.W. 50,000) known as
link protein.
The macromolecular complex is negatively charged and
highly hydrated; it interacts electrostatically with basic
charges on collagen fibrils, which define tissue space and
provide tensile strength. The interspersed proteoglycan ag-
gregates provide a hydrated, viscous gel for resistance to
compressive loads. Proteoglycans originating in different
tissues and exhibiting differences in molecular structure
are presumed to be products of different genes. Synthesis
and secretion of proteoglycans consist of several differ-
ent phases of the internal membrane systems of the cell.
Synthesis of the protein component occurs on ribosomes
attached to the rough endoplasmic reticulum, with translo-
cation of the newly synthesized polypeptide chains to the
cisternal side of the membrane. The polypeptide chains
travel through the cistemae of the endoplasmic reticu-
lum to the Golgi apparatus, where the oligosaccharide
side chains are synthesized by the addition of one sugar
residue at a time. Further modification of the sugar residues
(the conversion of selected residues of D-glucuronate to L-
iduronate, and sulfation) takes place after completion of
the oligosaccharide (Chapter 16). The fully synthesized
proteoglycans are then transferred from the Golgi appara-
tus, in the form of vesicles, to the cell membrane for the
purpose of secretion into the extracellular spaces.
The proteoglycan content in animal tissues appears to
change with aging. Tissues rich in keratan sulfate show a
continual increase in amount of this proteoglycan through-
out life. The amounts of chondroitin sulfate in cartilage
and in nucleus pulposus (of intervertebral disk) and of
hyaluronic acid in skin decrease with age. Administra-
tion of growth hormone to an older animal appears to
reverse the pattern of proteoglycan synthesis, making it
similar to that of a younger animal. Some of the effects
of growth hormone are mediated indirectly by a group
of peptides known as somatomedins, which are secreted
by the liver (and possibly by the kidney) under the influ-
ence of growth hormone (Chapter 31). Somatomedin A
(formerly known as sulfation factor) exhibits cartilage-
stimulating activity, in part by affecting the incorpora-
tion of sulfate into proteoglycans. Testosterone, a steroid
hormone (Chapter 34), increases the rate of hyaluronate
synthesis. Insulin deficiency causes diminished synthe-
sis of proteoglycans in rats that are rendered diabetic
experimentally; synthesis is restored to normal follow-
ing insulin administration. Some chronic complications of
diabetes mellitus, namely, accelerated vascular degenera-
tion, poor wound healing, and increased susceptibility to
