Protein Fibers and Proteoglycans
0.3 g of hydroxyproline per day in urine, which corre-
sponds to about 2.25 g of hydroxyproline-containing pro-
teins, most of which is collagen. Total protein catabolism
in a normal well-fed adult is about 300 g; thus, collagen
catabolism constitutes only about
% of total protein
Collagen turnover has important clinical implications.
The location, amount, type, and form of collagen depend
on the coordinated control of its synthesis and degradation.
In tissue injury (physical, chemical, infectious, or radia-
tion), repair process comprises regeneration and fibrous
connective tissue formation. Regeneration is the most de-
sirable form of repair: a cut surface of an epidermis is
replaced with new epidermis; scattered dead liver cells
are replaced with new liver cells.
Degradation products of type I collagen, namely
N-telopeptides, C-telopeptides, hydroxyproline, and the
collagen cross-links pyridinolone and deoxypyridinolone,
have been used as markers of osteoclast activity in bone
resorption. Collagen metabolite markers used for bone
formation reflecting osteoblast activity are procollagen
type I carboxyterminal propeptide and procollagen type I
N-terminal propeptide. Both of these propeptides are
cleaved byproducts generated from the conversion of pro-
collagen to tropocollagen. Osteocalcin and bone-specific
alkaline phosphatase are also used as bone formation
markers. Biochemical markers of bone turnover are used
for assessing and monitoring therapy in a number of dis-
eases of bone including osteoporosis (Chapter 37).
The cells of the body fall into three groups according to
labile cells multiply throughout life and are maintained at
an optimal level by continual proliferation of reserve cells.
Labile cells are found in all epithelial surfaces, the spleen,
and lymphoid and hematopoietic tissues. Stable cells have
the potential to regenerate but do not normally undergo
replication. However, under appropriate stimuli, they can
proliferate rapidly. Stable cells include parenchymal cells
of all glandular organs of the body and mesenchymal
cells (e.g., fibroblasts, smooth muscle cells, osteoblasts,
chondroblasts, and vascular endothelial cells). Permanent
cells do not undergo significant replication postnatally.
Nerve cells, skeletal muscle, and cardiac muscle cells are
In fibrous tissue scar formation (a tough mass of colla-
gen), normal cells are permanently lost. Many tissue in-
juries are repaired partly by regeneration and partly by scar
formation (e.g., healing of dermal cut, improperly united
bone fracture, and damaged liver). In tissues with perma-
nent cells, injury and repair result in the formation of scar
tissue only (e.g., myocardium). Although the liver norm-
ally undergoes repair by regeneration, chronic liver disease
resulting from ethanol abuse, some forms of malnutrition,
viral infections, or exposure to chemicals can lead to hep-
atic fibrosis (cirrhosis) with distortion of the liver archi-
tecture by newly synthesized collagen fibers. In hepatic
fibrosis, decreased collagenolytic activity and increased
collagen synthesis may determine the net collagen deposi-
tion. A defect in the turnover of collagen may be responsi-
ble for the pathogenesis of
idiopathic pulmonary fibrosis.
This usually fatal disorder of the lungs is characterized
by chronic inflammation of alveolar structures (alveolitis)
and progressive interstitial fibrosis. An active collagenase
in the lower respiratory tract may be responsible for sus-
tained collagen lysis followed by disordered resynthesis.
In rheumatoid arthritis, collagenous tissues of the joint
(including articular cartilage) are eroded by collagenases
and neutral proteinases derived from proliferating cells of
the synovial membrane and leukocytes. Therapeutic ap-
proaches may depend on regulation of collagen synthesis,
breakdown, or both.
In a large family with osteoarthritis, which is a disorder
of progressive degeneration of joint cartilage, in all af-
fected members the a (II) collagen contained a single-base
mutation converting the codon for arginine at position 519
to a codon of cysteine, an amino acid not found in normal
a(II). In unaffected members of the family, this mutation
does not occur.
Other disorders of collagen metabolism, heritable or
acquired, are discussed in Chapter 25.
Structure and Function
Elastin is a fibrous, insoluble protein that is not a glyco-
protein but is present with collagen in the connective
tissues. Connective tissues rich in elastic fibers exhibit
a characteristic yellow color. Elastic fibers are highly
branched structures responsible for physiological elas-
ticity. They are capable of stretching in two dimensions
and are found most notably in tissues subjected to con-
tinual high-pressure differentials, tension, or physical de-
formation. Elastin imparts to these tissues the properties
of stretchability and subsequent recoil that depend only
on the application of some physical force. Tissues rich in
elastic fibers include the aorta and other vascular connec-
tive tissues, various ligaments (e.g., ligamentum nuchae),
and the lungs. Microscopically, elastic fibers are thinner
than collagen fibers and lack longitudinal striations.
Elastin fibers can be separated into amorphous and fib-
rillar components. The amorphous component consists of
elastin, which is characterized by having 95% nonpolar
amino acid residues and two unique lysine-derived amino
acid residues, desmosine and isodesmosine.