Page 61 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioChemistry

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Encyclopedia of Physical Science and Technology EN006P-81 June 29, 2001 21:48

Glycoconjugates and Carbohydrates 845

CH 2 OH
O
H HOCH 2 O C O
H O
COO H O
H NH C CH
O HO H H CH 2
H O ( 1 4) OH
H H NH H NH
OH H O H
H C O
( 1 3) H NH
H OH CH 3
GlcA GlcNAc C O
FIGURE 24 Repeating unit of hyaluronate. This polysaccharide CH 2
is distributed throughout connective tissue and is the only mam- GlcNAc Asn
malian polysaccharide not covalently attached to protein.
Examples:
osteoathritis of the knee (an injectable) and in eye sur-
gery as a viscoelastic. In addition, cell surface recep-
tors have been identified that recognize the saccharides Asn Asn Glc
GlcNAc
in hyaluronate, and interaction with specific proteins is Man
responsible for the aggregate properties of connective tis- Gal
sue proteoglycans (see below). This diversity illustrates Neu5Ac
Fuc
that a single polysaccharide may have both informational Asn GalNAc
and physical roles in nature.
FIGURE 25 Schematic of a typical N-linked oligosaccharide.
Note the core structure, which contains two N-acetylglucosamine
IV. GLYCOCONJUGATES and three mannosyl residues. This is present in all units of this
type.
Structural analysis of proteins has shown that up to
thesis wherein the amino acid sequence is controlled by
half of naturally occurring proteins are subject to post-
the genetic one, the final structure of saccharides is rarely
translational modifications with the vast majority glyco-
so conserved. Thus, a given protein with several glycosy-
sylated. These covalent linkages involve several amino
lation loci is quite likely to have differing saccharide struc-
acids and have distinct structrual characteristics. In ad-
tures, even at the same amino acid site—all of them will
dition, a large number of lipids have covalently attached
still contain the pentasaccharide core noted above. These
carbohydrate, necessary for their biological functions.
The glycoproteins may be classified into two broad cat- various glycoforms give rise to a type of heterogeneity
that is difficult to characterize completely and may have
egories: N-linked and O-linked.
implications for function.
Thebiosynthesisofthesemoleculesisalsounusual.The
A. N-Linked Glycoproteins
saccharide is preassembled, not as the final structure but as
N-linked glycoproteins have carbohydrate covalently at- a common, 14-sugar, lipid-linked precursor that is trans-
tached to asparagine residues that occur in the sequence ferred en bloc to the target asparagine in a cotranslational
Asn-X-Ser/Thr, where X is any residue except proline. manner (Fig. 26). This saccharide unit (GlcNAc 2 -Man 9 -
This is a necessary but not sufficient key for glycosyla- Glc 3 ) is trimmed to a GlcNAc 2 -Man 5 structure that is then
tion since there are many examples of such sequences modified by addition of either more mannosyl residues or
that are not glycosylated even when others on the same by several sugars, including GlcNAc, Gal, NANA, and L-
polypeptide are substituted with sugar. The linking sugar fucose. The latter category is generally termed complex
is invariably N-acetylglucosamine, which is the termi- as opposed to those which contain GlcNAc and Man only
nal saccharide of the attached unit (Fig. 25). The number (high mannose).
of saccharides present in N-linked structures varies from
about 7 to 20 or more; branching is universal with some
B. O-Linked Glycoconjugates
structures having four separate branches (antennae). All of
the saccharides have a common core structure: GlcNAc- O-linked glycoconjugates have substantial diversity in
GlcNAc-Man 3 . The first mannose is β-linked (unusual) that the saccharide units may be covalently attached to
and the other two mannoses are attached α-1-3 and α-1-6, serine, threonine, tyrosine, hydroxylysine, or hydroxypro-
thus forming the initial branch point. Unlike protein syn- line residues. In addition, the type of glycosyl substitution