chapter 11
Heteropolysaccharides II: Proteoglycans and Peptidoglycans
p- D-Glucosylhydroxylysy! residue
o-Glucosyl (a1—2)-0-p-D-galactosyIhydroxylysy! residue
Glycosides of the collagen polypeptide chain.
The individual genes are identified by both collagen type
and the polypeptide chain. For example, COL1A2 gene
codes for type I collagen (COL1) and
(A2) polypep-
tide chain. The tissue distribution of collagens also varies
(Table 11-1).
Type I collagen consists of two identical chains of
and one chain of
it is the major connective tissue pro-
tein of skin, bone, tendon, dentin, and some other tissues.
Type II collagen consists of three identical chains of a 1
it is found in cartilage, cornea, vitreous humor, and neural
retinal tissue. Type III collagen consists of three identical
chains of a 1
(III); it is present, along with type I collagen,
in skin, arteries, and uterine tissue. Type IV collagens are
composed of a 1 (IV) to a5(IV) and are found in the base-
ment membranes of various tissues. Unlike collagen types
I, II, III, V, and XI which are fibrillar, type IV collagen is
not fibrillar in structure.
The synthesis of collagens in cultured cells has aided
the understanding of collagen biochemistry. The tissue
specificity of various types of collagen is also reflected
in cultured cells obtained from appropriate tissues. For
example, human fibroblasts and smooth muscle cells
synthesize both types I and III collagens; epithelial and
endothelial cells synthesize type IV collagen; and chon-
droblasts synthesize type II collagen.
Structure and Function
Each collagen molecule contains three polypeptide
chains coiled around each other in a triple helix. These
chains are called a-chains and are designated by Roman
numerals according to the chronological order of their dis-
covery. The three polypeptide chains may be identical or
may consist of two identical chains and one dissimilar
Each a-polypeptide chain consists of about 1000 amino
acid residues, of which every third following a glycine
is also a glycine. Thus, the molecular formula of an
a-chain may be written as (Gly-X-Y)
3 3 3
, where X and
Y represent amino acid residues other than glycine. In
mammalian collagens, about 100 of the X-positions are
occupied by proline residues, and 100 of the Y-positions
are occupied by 4-hydroxyproline residues. At a few
X-positions, 3-hydroxyproline residues are present; how-
ever, they only occur next to 4-hydroxyproline. Most hy-
droxyproline residues are present as the trans isomers.
Although all collagen polypeptides have the general struc-
ture (Gly-X-Y)„, differences between the various colla-
gen types are associated with the particular sequences of
amino acid residues in the X and Y positions. Hydroxypro-
line residues are not common in proteins; other than the
collagens, hydroxyproline residues are found in elastin,
acetylcholinesterase, and the Clq subcomponent of the
complement system (Chapter 35).
Another unique amino acid residue found in collagen is
hydroxylysine, which occurs at the Y-position. The num-
ber of hydroxylysine residues per polypeptide chain lies
in the range of 5 to 50. The hydroxylysine residues pro-
vide the sites for /î-O-glycosidic linkage with galactose
or glucose o ra(l —> 2) glucosylgalactose. The collagens
differ in their ratio of monosaccharide to disaccharide
residues, as well as in their total carbohydrate content.
For example, the carbohydrate contents of collagen from
skin, cartilage, and basement membrane are about 0.5%,
4%, and more than 10%, respectively. Because collagen
biosynthesis involves intracellular and extracellular post-
translational modifications (e.g., hydroxylation, glycosy-
lation, fibril formation, and formation of cross-links), a
given genetically determined collagen may show a great
deal of heterogeneity. This is particularly true for type I
Collagen also contains alanine residues in relatively
high quantities. The only amino acid not found in collagen
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