Download RCT Chapter 7

RCT Chapter 7
Aldoses and Ketoses; Representative monosaccharides. (a)Two
trioses, an aldose and a ketose. The carbonyl group in each is shaded.
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An aldose contains an aldehyde functionality
A ketose contains a ketone functionality
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Formation of maltose. A disaccharide
is formed from two monosaccharides
(here, two molecules of D-glucose)
when an —OH (alcohol) of one glucose
molecule (right) condenses with the
intramolecular hemiacetal of the other
glucose molecule (left), with elimination
of H2O and formation of a glycosidic
bond. The reversal of this reaction is
hydrolysis—attack by H2O on the
glycosidic bond. The maltose molecule,
shown here as an illustration, retains a
reducing hemiacetal at the C-1 not
involved in the glycosidic bond.
Because mutarotation interconverts the
α and β forms of the hemiacetal, the
bonds at this position are sometimes
depicted with wavy lines, as shown
here, to indicate that the structure may
be either α or β.
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Two common disaccharides.
Like maltose in these are
shown as Haworth
perspectives. The
common name, full
systematic name, and
abbreviation are given for
each disaccharide. Formal
nomenclature for sucrose
names glucose as the
parent glycoside, although
it is typically depicted as
shown, with glucose on
the left.
Polysaccharides
• Natural carbohydrates are usually found as
polymers
• These polysaccharides can be
– homopolysaccharides
– heteropolysaccharides
– linear
– branched
• Polysaccharides do not have a defined molecular
weight.
– This is in contrast to proteins because unlike
proteins, no template is used to make
polysaccharides
Glycogen
• Glycogen is a branched homopolysaccharide of
glucose
– Glucose monomers form (1  4) linked chains
– Branch-points with (1  6) linkers every 8–12
residues
– Molecular weight reaches several millions
– Functions as the main storage polysaccharide in
animals
Starch
• Starch is a mixture of two homopolysaccharides of
glucose
• Amylose is an unbranched polymer of (1  4)
linked residues
• Amylopectin is branched like glycogen but the
branch-points with (1  6) linkers occur every 24–
30 residues
• Molecular weight of amylopectin is up to 200 million
• Starch is the main storage polysaccharide in plants
Glycosaminoglycans
• Linear polymers of repeating disaccharide units
• One monomer is either
– N-acetyl-glucosamine or
– N-acetyl-galactosamine
• Negatively charged
– Uronic acids (C6 oxidation)
– Sulfate esters
• Extended hydrated molecule
– Minimizes charge repulsion
• Forms meshwork with fibrous proteins to form
extracellular matrix
– Connective tissue
– Lubrication of joints
Repeating units of some common glycosaminoglycans of extracellular
matrix.
Heparin and Heparan Sulfate
• Heparin is linear polymer, 3–40 kDa
• Heparan sulfate is heparin-like
polysaccharide but attached to proteins
• Highest negative charge density biomolecules
• Prevent blood clotting by activating protease
inhibitor antithrombin
• Binding to various cells regulates development
and formation of blood vessels
• Can also bind to viruses and bacteria and
decrease their virulence
Glycoconjugates: Glycoprotein
• A protein with small oligosaccharides attached
– Carbohydrate attached via its anomeric carbon
– About half of mammalian proteins are glycoproteins
– Carbohydrates play role in protein-protein recognition
– Only some bacteria glycosylate few of their proteins
– Viral proteins heavily glycosylated; helps evade the
immune system
Glycoconjugates: Proteoglycans
• Sulfated glucoseaminoglycans attached to a
large rod-shaped protein in cell membrane
– Syndecans: protein has a single
transmembrane domain
– Glypicans: protein is anchored to a lipid
membrane
– Interact with a variety of receptors from
neighboring cells and regulate cell growth
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This is heamaglutinin. The lectins
are carbohydrate-binding proteins
(not to be confused with
glycoproteins, which are proteins
containing sugar chains or residues)
that are highly specific for sugar
moieties, particularly, the high
specificity of plant lectins for
foreign glycoconjugates (e.g. those
of fungi, invertebrates and
animals). Lectins serve many
different biological functions in
animals, from the regulation of cell
adhesion to glycoprotein synthesis
and the control of protein levels in
the blood. They may also bind
soluble extracellular and
intercellular glycoproteins. Some
lectins are found on the surface of
mammalian liver cells that
specifically recognize galactose
residues
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Two families of membrane proteoglycans. (a) Schematic diagrams of a
syndecan and a glypican in the plasma membrane. Syndecans are held in the
membrane by hydrophobic interactions between a sequence of nonpolar amino
acid residues and plasma membrane lipids; they can be released by a single
proteolytic cut near the membrane surface. In a typical syndecan, the
extracellular amino-terminal domain is covalently attached to three heparan
sulfate chains and two chondroitin sulfate chains. Glypicans are held in the
membrane by a covalently attached membrane lipid (GPI anchor), but are shed if
the bond between the lipid portion of the GPI anchor and the oligosaccharide
linked to the protein is cleaved by a phospholipase. All glypicans have 14
conserved Cys residues, which form disulfide bonds to stabilize the protein
moiety, and either two or three glycosaminoglycan chains attached near the
carboxyl terminus, close to the membrane surface.
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Proteoglycan structure, showing the tetrasaccharide bridge. A typical
tetrasaccharide linker (blue) connects a glycosaminoglycan—
in this case chondroitin 4-sulfate (orange)—to a Ser residue in the core
protein. The xylose residue at the reducing end of the linker is joined by
its anomeric carbon to the hydroxyl of the Ser residue.
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Proteoglycan aggregate of the
extracellular matrix. Schematic
drawing of a proteoglycan with
many aggrecan molecules. One
very long molecule of hyaluronan
is associated noncovalently with
about 100 molecules of the core
protein aggrecan. Each aggrecan
molecule contains many covalently
bound chondroitin sulfate and
keratan sulfate chains. Link
proteins at the junction between
each core protein and the
hyaluronan backbone mediate the
core protein–hyaluronan
interaction. The micrograph
shows a single molecule of
aggrecan, viewed with the atomic
force microscope.
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Interactions between cells
and the extracellular
matrix. The association
between cells and the
proteoglycan of the
extracellular matrix is
mediated by a membrane
protein (integrin) and by an
extracellular protein
(fibronectin in this
example) with binding sites
for both integrin and the
proteoglycan. Note the
close association of collagen
fibers with the fibronectin
and proteoglycan.
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Bacterial LPS. Schematic diagram of the LPS
of the outer membrane of Salmonella
typhimurium. Kdo is 3-deoxy-D-mannooctulosonic acid (previously called
ketodeoxyoctonic acid); Hep is L-glycero-Dmanno-heptose; AbeOAc is abequose (a 3,6dideoxyhexose) acetylated on one of its
hydroxyls. There are six fatty acid residues in the
lipid A portion of the molecule. Different bacterial
species have subtly different LPS structures, but
they have in common a lipid region (lipid A), a
core oligosaccharide also known as endotoxin,
and an “O-specific” chain, which is the principal
determinant of the serotype (immunological
reactivity) of the bacterium. The outer membranes
of the gram-negative bacteria S. typhimurium and
E. coli contain so many LPS molecules that the
cell surface is virtually covered with O-specific
chains.