Download Polysaccharides Homo- and heteroglycans

2014-10-29
Polysaccharides
Homo- and heteroglycans
Polysaccharides are divided into two
broad classes
1. Homoglycans, or homopolysaccharides,
which are polymers containing only one type
of monosaccharide residue
2. Heteroglycans, or heteropolysaccharides,
which are polymers containing more than
one type of monosaccharide residue
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Polysaccharides - Classification
Structural
Polysaccharides
Polysaccharides
Most polysaccharides can also be classified
according to their biological roles
1. Storage polysaccharides: starch and
glycogen
2. Structural polysaccharides: cellulose
and chitin
Storage
Polysaccharides
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Starch and glycogen
• Starch and glycogen are polymers of
α D glucopyranose, and are known as
storage polysaccharides
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Starch - a very large glucanis the plant energy reserve
a. The repeating linear unit
is two Glc residues in α-1→4
linkage
b. The helical structure of
the non-branched component
amylose
Amylopectin, a form of starch, have α 1-4 glycosidic
bonds and α 1-6 glycosidic bonds.
The actual distance between branch points averages 24 to 30 glucose residue.
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Starch digestion is sequential
•α-amylose sequentially digests disaccharides from nonreducing ends of polymers; products are maltotriose,
maltose, and oligosaccharides with branchpoints
(dextrins)
•α-glucosidase cleaves maltotriose and maltose to
component glucose residues
•α-dextrinase (debranching enzyme) cleaves both α-1→4
and α-1→6 linkages to degrade dextrins to monomers
The major form of storage polysaccharide in animals is
glycogen.
• Glycogen is found mainly in the liver (where it may
amount to as much as 10% of liver mass) and skeletal
muscle (where it accounts for 1 to 2% of muscle
mass).
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Glycogen.
•Glycogen can be hydrolyzed by both α- and β-amylases, yielding glucose and
maltose as products, respectively, and can also be hydrolyzed by glycogen
phosphorylase, an enzyme present in liver and muscle tissue, to release
glucose-1-phosphate.
Cellulose
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Polymer of β-D-glucose attached by β(1,4) linkages
Yields glucose upon complete hydrolysis
Partial hydrolysis yields cellobiose
Most abundant of all carbohydrates
• Cotton flax: 97-99% cellulose
• Wood: ~ 50% cellulose
• Gives no color with iodine
• Held together with lignin in woody plant tissues
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Cellulose
• Cellulose monomers (βD-glucopyranose) are
linked together through
β1→4 glycosidic bonds
by condensation.
Cellulose
structure•H-bonded sheets made
up of linear polymer,
where residues are
turned 180o relative to
their neighbors
•H bonds are
intrachain
as well as
interchain
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A short segment of chitin
Linear polymer of N-acetylglucosamine sugars linked by β 1→4
bonds. Each GlcNAc residue is rotated 180o relative to its neighbors
Heteroglycans
• High molecular weight carbohydrate polymers that
contain more than one kind of monosaccharides.
• Major classes found in animals are N and O-linked
glycans attached to proteins.
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Heteropolysaccharides of the animal extracellular matrix
(ECM) and cell surface, termed glycosaminoglycans
(GAGs), play both structural and recognition roles
•Repeating disaccharides make up these polymers, and
component sugars are negatively charged derivatives
(uronic acids and sulfated sugars) and amino sugars (usually
acetylated )
•Some GAGs have tissue-specific distribution, and all but
heparin are found more often in complex structures
(proteoglycans) than in isolation
Structure of Glycosaminoglycans (GAGs)
• Glycosaminoglycans are
long, unbranched,
heteropolysaccharide
chains generally
composed of a repeating
disaccharide unit [acidic
sugar–amino sugar]n.
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Heteroglycans, or heteropolysaccharides,
• Common
monosaccharide
derivatives
in
heteropolysaccharides include:
the amino sugars: D-glucosamine and D-galactosamine
their derivatives: N-acetylneuraminic acid and
N-acetylmuramic acid
and simple sugar acids: glucuronic and iduronic acids.
Some monosaccharide units found in
glycosaminoglycans.
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Classification of the glycosaminoglycans
(GAGs)
• The six major classes of glycosaminoglycans are
divided according to monomeric composition, type of
glycosidic linkages, and degree and location of
sulfate units.
• The specific GAGs of physiological significance are:
hyaluronic acid, dermatan sulfate, chondroitin sulfate,
heparin, heparan sulfate, and keratan sulfate.
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Highly glycosylated proteins carry up to 99% carbohydrate
by weight
Proteoglycans are components of the ECM, made up of GAGs, core
protein, and link proteins in a complex structure
•Hyaluronate forms a backbone onto which large core proteins
are attached via linker proteins; other GAGs are attached
to core proteins via association with protein-linked
glycans. The end structures are millions of daltons, and
can vary even in core and linker protein identity.
•Roles of proteoglycans include both support, as described for
GAGs, and recognition. Proteoglycans can bind to
growth factors, allowing their presentation in the context
of the ECM and limiting the target distance of the
growth factors.
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Hyaluronic acid is among the largest glycans
•The repeating disaccharide is Glucuronate β-1→3-GlcNAc, in β-1→4
linkages so the structure of hyaluronate is an extended helix
•The numerous anionic groups result in a rigid and highly hydrated
molecule- high viscosity in solution and structurally responsive to
shear forces.
•At low shear, high resistance as molecules are relatively disordered; at
high shear, molecules line up with the direction of the force so little
resistance.
•This allows function as shock absorber and lubricant.
Heparan SO4 is a ubiquitous cell surface and ECM GAG, and
most variable in composition. The repeating disaccharide is
Iduronate SO4α1→4 Sulfo-glucosamine SO4 .
Heparin is similar to heparan sulfate but is less variable.
This is the most highly charged GAG- there are on average 2.5
SO4 groups per disaccharide- and is the most negatively charged
molecule in animal tissues.
Heparin is synthesized and held within mast cells lining arteries, is
released after injury and inhibits the blood clotting cascade by
enhancing anti-thrombin activity.
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Heparin
Heparin, a soluble glycosaminoglycan found in granules of mast cells, has a
structure similar to that of heparan sulfates, but is relatively highly sulfated.
made & released from mast cells in lungs & liver
also associated with luminal surface of endothelium
anticoagulant
– forms complex with antithrombin III
– this complex binds to thrombin, inactivating it
– as a result, clot growth is limited
– fast-acting, making it therapeutically useful
Repeating units of glycosaminoglycans
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GAG Localization
• Hyaluronate: synovial fluid, vitreous humor,
• Chondroitin sulfate: cartilage, bone, heart valves
• Heparan sulfate: basement membranes,
components of cell surfaces contains higher acetylated
glucosamine than heparin
• Heparin: component of intracellular granules of mast cells
lining the arteries of the lungs, liver
• Dermatan sulfate: skin, blood vessels, heart valves• Keratan sulfate: cornea, bone, cartilage aggregated with
chondroitin sulfates
• Glycoconjugates = carbohydrate derivatives
in which one or more carbohydrate chains
are linked to a protein, peptide chain, or
lipid:
– Proteoglycans, peptidoglycans, glycoproteins,
glycolipids
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Proteoglycans are glycosaminoglycans that are
covalently linked to serine residues of specific core
proteins.
The linkage of GAGs to the protein core involves a specific
trisaccharide composed of two galactose residues and a xylose residue
(GAG-GalGalXyl-O-CH2-protein)
Proteoglycans
• The
disaccharide
units
contain either of two
modified
sugars
N-acetylgalactosamine
(GalNAc)
or
N-acetylglucosamine
(GlcNAc) and a uronic acid
such as glucuronate or
iduronate.
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Proteoglycan (the protein-carbohydrate) complex in
cartilage
A major function of GAGs is the formation of a matrix to hold
together the protein components of the skin and connective tissue
• In addition, carbohydrates are covalently linked
with a variety of other molecules.
• Carbohydrates linked to lipid molecules, or
glycolipids , are common components of biological
membranes.
• Proteins that have covalently linked carbohydrates
are called glycoproteins .
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Glycoproteins
• Many proteins carry covalently attached oligosaccharide or
polysaccharide chains
• These complexes are known as glycoproteins, and they serve
many different functions
GLYCOPROTEIN FUNCTIONS
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Structural→proteoglycans
Transport proteins→transferrin
Enzymes
Antibodies
Antifreeze protein in Antarctic fish -carbohydrate forms
H-bonds with water, preventing growth of ice crystals
Recognition phenomena-cell to molecule, cell-virus and cellcell
Insulin receptor is a glycoprotein
CD4 receptor is site of HIV attachment is a glycoprotein
Immunoglobulins are examples of glycoproteins.
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Glycoproteins
• Proteins that contain covalently-bound oligosaccharides, either to
serine (O-Glycosidic linkage) or asparagine (N-glycosidic linkage)
• Oligosaccharide chains exhibit great variability in sugar sequence
and composition
O-Glycosidic
and N-glycosidic linkages
Chapter 8
Mucins: salivary glycoproteins
mol wt ~ 106
~800 short
(disaccharide)
side chains
terminal sugar is sialate
– anionic sugar
– at end of glycochains
of many glycoproteins
very hydrophilic,
extended structure
~
~
galNAc
sialate
–
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Mucins: modification & aggregation
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sialidase (neuraminidase)
– catalyzes hydrolysis
of sialates from mucins
– secreted by oral bacteria
products:
– less hydrophilic,
less H2O-soluble,
more folded,
more aggregated
– part of the enamel pellicle
& dental plaque matrix
~
~
The blood group antigens are important group of
oligosaccharides
• On some cells these are attached as O-linked glycans
to membrane proteins
• The antigens which determine blood types belong to
glycoproteins and glycolipids.
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There are three types of blood-group antigens: O, A, and B. They
differ only slightly in the composition of carbohydrates
• The A and B antigens
are formed by addition
of GalNAc or Gal,
respectively to the Ooligosaccharide
Peptidoglycans
• The cell of many bacteria are made of
peptydoglycans, which are heteroglycan chains linked
to peptides
• Its polysaccharide component consists of linear
chains of alternating β(1→4)-linked
N-acetylglucosamine (GlcNAc) and N-acetylmuramic
acid (NAM)
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Glycan moiety of peptidoglycan
Peptidoglycan
• glycan backbone
– muramic acid (NAM)
– N-acetylglucosamine
• peptide side chain
• peptide cross-bridge
– D- and L- amino acids
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Bacterial Cell Walls
Composed of 1 or 2 bilayers and
peptidoglycan shell
• Gram-positive: One bilayer and
thick peptydoglycan outer shelll
Gram-positive
outer shell
• Gram-negative: Two bilayers
with thin peptydoglycan shell in
betweenhell in between
• Gram-positive:
pentaglycine
bridge connects tetrapeptides
• Gram-negative: direct amide
bond between tetrapeptidesetween
Gram-negative
Peptidoglycan: Polymer of disaccharide
N-acetylglucosamine (NAG) & N-acetylmuramic acid (NAM)
Linked by polypeptides
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Peptide cross-bridges
Gram-negative:
Amino acids directly joined
via cross-bridge
Gram-positive:
Glycine pentapeptide bridge
joins amino acids
Gram-Negative Outer Membrane
Bilayer membrane outside the peptidoglycan contains phospholipids,
proteins, and lipopolysaccharide (LPS)
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Lipopolysaccharide (LPS)
• Lipopolysaccharide occurs on the outer membrane of gramnegative bacteria such as E. coli and Salmonella typhimurium
• Also known as endotoxin
• The lipid A portion of the lipopolysaccharides of some bacteria
is toxic to humans (e.g. it is responsible for the dangerously
lowered blood pressure that occurs with toxic shock syndrome in
G(-) bacterial infections in humans
– Dead cells release lipid A when cell wall disintegrates
– May trigger fever, vasodilation, inflammation, shock, and
blood clotting
Gram-Positive cell walls
• Gram-positive cell walls contain teichoic acids
• Teichoic acids:
– Lipoteichoic acid links to plasma membrane
– Wall teichoic acid links to peptidoglycan
• May regulate movement of cations
• Polysaccharides provide antigenic variation
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Bacterial cell walls
Teichoic acids are polymers of glycerol or ribitol
(linked by phosphodiester bonds) with GlcNAc
and D-Ala side chains
These anionic molecules on the surface of Grampositive bacteria- up to 50% dry weight of the cell
wall- can be linked to peptidoglycan at NAcGlc or
NAcMur or can be linked to membrane lipid.
They play structural role(s) and can be important
to survival and virulence.
Comparison of Gram-Positive and Gram-Negative
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