12. • Those containing an O-
glycosidic linkage (O-
linked), involving the
hydroxyl side chain of
serine or threonine
(and sometimes also
tyrosine) and a sugar
such as N-
acetylgalactosamine
(GalNAc-Ser[Thr])
13. • Those containing an N-
glycosidic linkage (N-
linked), involving the
amide nitrogen of
asparagine and N-
acetylglucosamine
(GlcNAc-Asn)
14. • Those linked to the
carboxyl terminal amino
acid of a protein via a
phosphoryl-
ethanolamine moiety
joined to an
oligosaccharide (glycan),
which in turn is linked via
glucosamine to
phosphatidylinositol (PI)
15.
16.
17.
18. • Lectins are carbohydrate-binding proteins that
agglutinate cells or precipitate
glycoconjugates; a number of lectins are
themselves glycoproteins.
• The specificity of a lectin is usually defined by
the sugars that are best able to inhibit its
ability to cause agglutination or precipitation
19.
20. • Mucins have a high Content of O-Linked
Oligosaccharides & Exhibit repeating amino
acid Sequence
• Both secretory and membrane-bound mucins
occur
21. • Mucus secreted by the gastrointestinal,
respiratory, and reproductive tracts is a
solution containing about 5% mucins
• Mucus has a high viscosity and often forms a
gel because of its content of mucins
• The high content of NeuAc and sulfate
residues found in many mucins gives them a
negative charge
22. • Mucins help to lubricate and form a protective
physical barrier on epithelial surfaces
• They are highly resistant to proteolysis
because the density of oligosaccharide chains
makes it difficult for proteases to access their
polypeptide backbones.
23. • Membrane-bound mucins participate in cell-cell
interactions. They may also mask cell surface
antigens.
• Many cancer cells form large amounts of mucins
that mask surface antigens and protect the
cancer cells from immune surveillance.
• Mucins also carry cancer-specific peptide and
carbohydrate epitopes. Some of these have been
used to stimulate an immune response against
cancer cells.
24.
25.
26. • N-Linked glycoproteins are the major class of
glycoproteins, including both membrane-
bound and circulating glycoproteins.
• They are distinguished by the presence of the
asparagine— N-acetylglucosamine linkage
27. There are three major
classes of N-linked
oligosaccharides:
complex,
highmannose, and
hybrid. All three
classes have the same
branched
pentasaccharide,
Man3GlcNAc2, bound
to asparagine, but
differ in their outer
branches
28.
29. The presence of the common
pentasaccharide in N-linked glycoproteins
is explained by the fact they share an initial
common mechanism of biosynthesis, in
which a branched oligosaccharide is
synthesized attached to dolichol
pyrophosphate
30.
31. GLYCANS ARE INVOLVED IN THE BINDING
OF VIRUSES, BACTERIA, & SOME PARASITES
TO HUMAN CELLS
• Influenza virus A binds to cell surface glycoprotein receptor
molecules containing N-acetylneuraminic acid via a
hemagglutinin protein. The virus also has a neuraminidase
that plays a key role in allowing elution of newly
synthesized progeny from infected cells. If this process is
inhibited, spread of the viruses is markedly diminished.
Inhibitors of this enzyme (eg, zanamivir, oseltamivir) are
now available for use in treating patients with influenza.
Influenza viruses are classified according to the type of
hemagglutinin (H) and neuraminidase (N) that they
possess. There are at least 16 types of hemagglutinin and
nine types of neuraminidase. Thus, avian influenza virus is
classified as H5N1
32. • Human immunodeficiency virus type 1 (HIV-
1), the cause of AIDS, attaches to cells via one
of its surface glycoproteins (gp 120) and uses
another surface glycoprotein (gp 41) to fuse
with the host cell membrane
33. • Helicobacter pylori is the major cause of
peptic ulcers. It binds to at least two different
glycans present on the surfaces of epithelial
cells in the stomach allowing it to establish a
stable attachment site to the stomach lining.
34. • To reach the plasma membrane of an oocyte,
a sperm has to traverse the zona pellucida
(ZP), a thick, transparent, noncellular
envelope that surrounds the oocyte. The
glycoprotein ZP3 is an O-linked glycoprotein
that functions as a sperm receptor
35. • Rheumatoid arthritis is associated with an
alteration in the glycosylation of circulating
immunoglobulin G (IgG) molecules
36. • Mannose-binding protein can also bind sugars
when they are present on the surfaces of
bacteria, fungi, and viruses, preparing these
pathogens for opsonization or for destruction
by the complement system
37. OVERVIEW OF GLYCOSAMINOGLYCANS
• Glycosaminoglycans are large complexes of
negatively charged hetero polysaccharide
chains
• They are generally associated with a small
amount of protein, forming proteoglycans,
which typically consist of over 95%
carbohydrate.
38. • Glycosaminoglycans have the special ability to
bind large amounts of water, thereby
producing the gel-like matrix that forms the
basis of the body’s ground substance, which,
along with fibrous structural proteins such as
collagen and elastin, and adhesive proteins
such as fibronectin, make up the extracellular
matrix (ECM
39. • The hydrated glycosaminoglycans serve as a
flexible support for the ECM, interacting with
the structural and adhesive proteins, and as a
molecular sieve, influencing movement of
materials through the ECM
40. • The viscous, lubricating properties of mucous
secretions also result from the presence of
glycosaminoglycans, which led to the original
naming of these compounds as
mucopolysaccharides
