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DBT2117: Biochemistry (I)
Lecture 16
Carbohydrates continued
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Polysaccharides have many functions
• Polysaccharides have many biological functions, particularly for energy storage and
for structural support.
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Storage polysaccharides • The principal storage polysaccharides are
amylose and amylopectin, which together
constitute starch in plants, and glycogen,
which is stored in animal and microbial cells
as granules.
• Glycogen is deposited in the liver, which acts
as a central energy storage organ in many
animals.
• Glycogen is also abundant in muscle tissue, where it is more immediately available for
energy release.
Molecular structures for storage polysaccharides • Amylose, amylopectin, and glycogen are all homopolysaccharides of α‐D‐glucopyranose
(called glucans, which means polymers of glucose)
• Amylose is linear (α14)… Amylose forms a helical structure.
• amylopectin and glycogen are branched because they contain both α14 and α16.
Amylose
Reducing end
Non‐reducing end
Amylopectin 國立交通大學生物科技學系蘭宜錚老師
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Molecular structures for structural polysaccharides • Cellulose is the most abundant polymer in the biosphere
• Similar to amylose and glycogen, cellulose is also a glucan
• HOWEVER! It is β‐14 bonding
• β‐14 makes each glucose flipped by 180° with respect to its neighbor
• The parallel cellulose chains are linked
together by a network of hydrogen bonds.
• This bonding gives cellulose a strong
hydrogen bonding network, providing
a great mechanical strength.
Plant biomass
• Most plant biomass is composed of cellulose, hemicellulose, and lignin
• Cellulose: linear β‐1‐4 glucose polymer
• Hemicellulose: Branched heteropolymers containing glucose, xylose, arabinose, mannose, galactose, etc. (in some cases also contains sugar derivatives).
• Lignin: crosslinked aromatics which provides strength to plants (such as the hardness in
wood and bark)
• Plant biomass is the most abundant
bioresource we have on earth
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Chitins
• Similar to cellulose, chitin is a β14 polymer. It is a polymer of NAG (N‐acetylglucosamine)
• Chitin is found in many organisms
• insect shells, crab shell, etc
Structural polysaccharides in vertebrate animals
•
The major structural polysaccharides in vertebrate animals are the glycosaminoglycans, formerly called
mucopolysaccharides.
•
Important examples are the chondroitin sulfates and
keratan sulfates of connective tissue, the dermatan
sulfates of skin, and hyaluronic acid.
•
All are polymers of repeating disaccharide units, in
which one of the sugars is either N‐acetylgalactosamine
or N‐acetylglucosamine or one of their derivatives.
•
All are acidic (anionic), through the presence of either sulfate or carboxylate groups. 國立交通大學生物科技學系蘭宜錚老師
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Structural polysaccharides in vertebrate animals
Heparin
•
A highly sulfated glycosaminoglycan is heparin.
•
Heparin appears to be a natural anticoagulant and is found in many body tissues.
•
It binds strongly to a blood protein, antiprothrombin III, and the complex inhibits
enzymes of the blood clotting process.
•
Therefore, heparin is used medicinally to inhibit clotting in blood vessels.
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Glycoproteins
• Glycoproteins are proteins that contain oligo‐ or polysaccharide chains.
• These glycosylation serve wide purposes including cell adhesion & recognition
• Oligosaccharides can attach to proteins through N‐link or O‐link.
Glycoproteins: Blood types
• Blood types are referring to the blood group antigens
Fucα‐1,2‐Galβ‐
Would be useful to convert A & B blood to O blood. How would we do this?
GalNAcα‐1,3‐(Fucα‐1,2)‐Galβ‐
Galα‐1,3‐(Fucα‐1,2)‐ Galβ‐
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Structural polysaccharides in bacterial cell surface
• On the outside of bacteria cell surface, there is a layer of peptidoglycan (polysaccharide‐
peptide complex). Gram positive bacteria is shown below:
N‐Acetylmuramic acid
N‐Acetylglucosamine
Peptidoglycan layer has large crosslink network
Formation of peptidoglycan
How do we get UDP‐NAM?
In every step of adding an amino acid. What is a likely co‐reactant not shown here?
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Penicillin
• Penicillin works by binding to the
peptide chain, inhibiting its cross linking
with the other chains
• Cross‐links between
adjacent peptidoglycan
chains are formed by the
action of a
transpeptidase enzyme.
• Penicillin, a structural
analog of the natural
substrate, reacts with
the active form of the
enzyme to form an
inactive covalent
complex that resembles
the enzyme–substrate
complex.
Polysaccharides are often observed on cell surface
• Polysaccharides are often found on the outside of cells.
• They can bind to both proteins and lipids (lipopolysaccharides).
• As such, these can potentially be used as biomarkers
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Influenza virus
• The structure of the influenza
virus:
• The 13,600‐nucleotide RNA
genome is packaged within
the sphere, about 120 nm in
diameter.
• The spikes on the virion
exterior include the
hemagglutinin molecule and
a spike that terminates in four
neuraminidase molecules.
• Hemagglutinin binds to N‐acetylneuraminic
acid (Sialic acid) commonly found in cell
surface glycoproteins and/or glycolipids.
• At the end of infection cycle, Influenza virus
uses neutraminidase to cleave sialic acid in
order to release itself from the cell.
Influenza virus
• Based on the crystal structure of
neuramidase complexed with sialic acid,
structural analogs of sialic acid were
developed with the potential to inhibit
the enzyme.
• Once neuramidase is inhibited, viral
particles cannot leave the infected cell.
• Partial model of the neuraminidase‐
zanamivir complex, showing amino
acid residues that are close to the
binding site for the inhibitor.
• Oseltamivir (marketed as Tamiflu) was
used to treat influenza outbreaks in
2009 & 2013)
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