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Carbohydrates II
Andy Howard
Introductory Biochemistry, Fall 2009
22 September 2009
Biochem: Carbohydrates II
09/22/2009
Sugars and polysaccharides
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Sugars are vital as energy sources, and
they also serve as building blocks for
lipid-carbohydrate and proteincarbohydrate complexes
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Biochem: Carbohydrates II
p. 2 of 58
Plans for Today
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Sugar Concepts
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Monosaccharides
Cyclization
Reducing and
nonreducing
sugars
Sugar Derivatives
Oligosaccharides
Glycosides
09/22/2009
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Polysaccharides
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Starch & glycogen
Cellulose and
chitin
Glycoconjugates
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Biochem: Carbohydrates II
Proteoglycans
Peptidoglycans
Glycoproteins
p. 3 of 58
Sugar nomenclature
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All sugars with m ≤ 7 have specific
names apart from their enantiomeric
(L or D) designation,
e.g. D-glucose, L-ribose.
The only 7-carbon sugar that routinely
gets involved in metabolism is
sedoheptulose, so we won’t try to
articulate the names of the others
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Biochem: Carbohydrates II
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Fischer projections
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Convention for drawing openchain monosaccharides
If the hydroxyl comes off
counterclockwise relative to
the previous carbon, we draw
it to the left;
Clockwise to the right.
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Biochem: Carbohydrates II
Emil
Fischer
p. 5 of 58
Cyclic sugars
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Sugars with at least four carbons can
readily interconvert between the openchain forms we have drawn and fivemembered(furanose) or six-membered
(pyranose) ring forms in which the
carbonyl oxygen becomes part of the ring
There are no C=O bonds in the ring forms
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Furanoses
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Formally derived from
structure of furan
Hydroxyls hang off of the
ring; stereochemistry
preserved there
Extra carbons come off at 2
and 5 positions
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Biochem: Carbohydrates II
1
5
2
4
3
furan
p. 7 of 58
1
Pyranoses
6
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Formally derived from
structure of pyran
Hydroxyls hang off of the
ring; stereochemistry
preserved there
Extra carbons come off at 2
and 6 positions
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Biochem: Carbohydrates II
2
3
5
4
pyran
p. 8 of 58
How do we cyclize a sugar?
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Formation of an internal hemiacetal or
hemiketal (see a few slides from here)
by conversion of the carbonyl oxygen
to a ring oxygen
Not a net oxidation or reduction;
in fact it’s a true isomerization.
The molecular formula for the cyclized
form is the same as the open chain
form
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Family tree of aldoses
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Simplest: D-, L- glyceraldehyde (C3)
Add —CHOH: D,L-threose, erythrose (C4)
Add —CHOH:
D,L- lyxose, xylose, arabinose, ribose (C5)
Add —CHOH:
D,L-talose, galactose, idose, gulose,
mannose, glucose, altrose, allose (C6)
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Family tree of ketoses
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Simplest: dihydroxyacetone (C3)
Add —CHOH: D,L-erythrulose (C4)
Add —CHOH:
D,L- ribulose, xylulose (C5)
Add —CHOH:
D,L-sorbose, tagatose, fructose, psicose
(C6)
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Haworth projections
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…provide a way of
keeping track the chiral
centers in a cyclic sugar,
as the Fischer
projections enable for
straight-chain sugars
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Biochem: Carbohydrates II
Sir Walter
Haworth
p. 12 of 58
O
The anomeric carbon
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C
In any cyclic sugar
(monosaccharide, or single unit of
an oligosaccharide, or
polysaccharide) there is one
carbon that has covalent bonds to
two different oxygen atoms
We describe this carbon as the
anomeric carbon
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Biochem: Carbohydrates II
O
p. 13 of 58
iClicker quiz, question 1
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Which of these is a furanose sugar?
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iClicker quiz, question 2
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Which carbon is the anomeric
carbon in this sugar?
(a) 1
(b) 2
(c) 5
(d) 6
(e) none of these.
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iClicker, question 3
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How many 7-carbon D-ketoses are
there?
(a) none.
(b) 4
(c) 8
(d) 16
(e) 32
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Biochem: Carbohydrates II
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a-Dglucopyranose
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One of 2 possible
pyranose forms of Dglucose
There are two
because the anomeric
carbon itself becomes
chiral when we
cyclize
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Biochem: Carbohydrates II
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b-Dglucopyranose
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Differs from aD-glucopyranose only
at anomeric
carbon
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Biochem: Carbohydrates II
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Count carefully!
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It’s tempting to think that hexoses are
pyranoses and pentoses are furanoses;
But that’s not always true
The ring always contains an oxygen, so
even a pentose can form a pyranose
In solution: pyranose, furanose, openchain forms are all present
Percentages depend on the sugar
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Biochem: Carbohydrates II
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Substituted monosaccharides
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Substitutions on the various positions
retain some sugar-like character
Some substituted monosaccharides are
building blocks of polysaccharides
Amination, acetylamination,
carboxylation common
O
OOH
HO
HO
O
OH
GlcNAc HNCOCH
3
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HO
HO
D-glucuronic acid
HO
(GlcUA)
Biochem: Carbohydrates II
O
OH
p. 20 of 58
6
Sugar acids
(fig. 7.10)
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Gluconic acid:
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5
4
1
3
D--gluconolactone
2
glucose carboxylated @ 1 position
In equilibrium with lactone form
Glucuronic acid:
glucose carboxylated @ 6 position
Glucaric acid:
glucose carboxylated @ 1 and 6 positions
Iduronic acid: idose carboxylated @ 6
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Sugar alcohols (fig.7.11)
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Mild reduction of sugars convert aldehyde
moiety to alcohol
Generates an additional asymmetric
center in ketoses except dihyroxyacetone
These remain in open-chain forms
Smallest: glycerol
Sorbitol, myo-inositol, ribitol are important
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Sugar esters
(fig. 7.13)
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Phosphate esters of
sugars are significant
metabolic intermediates
5’ position on ribose is
phosphorylated in
nucleotides
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Biochem: Carbohydrates II
Glucose 6phosphate
p. 23 of 58
OH
Amino sugars
HO
HO
GlcNAc
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O
OH
HNCOCH3
Hydroxyl at 2- position of hexoses is
replaced with an amine group
Amine is often acetylated (CH3C=O)
These aminated sugars are found in
many polysaccharides and glycoproteins
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Hemiacetals and hemiketals
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Hemiacetals and hemiketals are compounds
that have an –OH and an –OR group on the
same carbon
Cyclic monosaccharides are hemiacetals &
hemiketals
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Acetals and ketals
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Acetals and ketals have two —OR groups on
a single carbon
Acetals and ketals are found in glycosidic
bonds
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Oligosaccharides and other
glycosides
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A glycoside is any compound in which
the hydroxyl group of the anomeric
carbon is replaced via condensation with
an alcohol, an amine, or a thiol
All oligosaccharides are glycosides, but
so are a lot of monomeric sugar
derivatives, like nucleosides
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Sucrose: a glycoside
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A disaccharide
Linkage is between
anomeric carbons of
contributing
monosaccharides,
which are glucose
and fructose
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Other disaccharides
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Maltose
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Cellobiose
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glc-glc with a-glycosidic bond from left-hand glc
Produced in brewing, malted milk, etc.
b-glc-glc
Breakdown product from cellulose
Lactose: b-gal-glc
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Milk sugar
Lactose intolerance caused by absence of
enzyme capable of hydrolyzing this glycoside
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Reducing sugars
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Sugars that can undergo ring-opening to
form the open-chain aldehyde compounds
that can be oxidized to carboxylic acids
We describe those as reducing sugars
because they can reduce metal ions or
amino acids in the presence of base
Benedict’s test:
2Cu2+ + RCH=O + 5OH- 
Cu2O + RCOO- + 3H2O
Cuprous oxide is red and insoluble
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Biochem: Carbohydrates II
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Ketoses are reducing sugars
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In presence of base a ketose can
spontaneously rearrange to an aldose
via an enediol intermediate, and then
the aldose can be oxidized.
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Sucrose: not a reducing sugar
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Both anomeric carbons
are involved in the
glycosidic bond, so they
can’t rearrange or open
up, so it can’t be oxidized
Bottom line: only sugars
in which the anomeric
carbon is free are
reducing sugars
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Reducing & nonreducing ends
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Typically, oligo and polysaccharides have a
reducing end and a nonreducing end
Non-reducing end is the sugar moiety
whose anomeric carbon is involved in the
glycosidic bond
Reducing end is sugar whose anomeric
carbon is free to open up and oxidize
Enzymatic lengthening and degradation of
polysaccharides occurs at nonreducing end
or ends
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Nucleosides
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Anomeric carbon of
ribose (or deoxyribose) is
linked to nitrogen of RNA
(or DNA) base
(A,C,G,T,U)
Generally ribose is in
furanose form
This is an example of an
N-glycoside
09/22/2009
Biochem: Carbohydrates II
Diagram courtesy of
World of Molecules
p. 34 of 58
Polysaccharides
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Homoglycans: all building blocks same
Heteroglycans: more than one kind of
building block
No equivalent of genetic code for
carbohydrates, so long ones will be
heterogeneous in length and branching,
and maybe even in monomer identity
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Categories of polysaccharides
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Storage homoglycans (all Glc)
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Structural homoglycans
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Starch: amylose (a(14)Glc) , amylopectin
Glycogen
Cellulose (b(14)Glc)
Chitin (b(14)GlcNAc)
Heteroglycans
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Glycosaminoglycans (disacch.units)
Hyaluronic acid (GlcUA,GlcNAc)(b(1  3,4))
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Storage polysaccharides
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Available sources of glucose for energy
and carbon
Long-chain polymers of glucose
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Starch (amylose and amylopectin):
in plants, it’s stored in 3-100 µm granules
Glycogen
Branches found in all but amylose
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Amylose
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Unbranched, a-14 linkages
Typically 100-1000 residues
Not soluble but can form hydrated
micelles and may be helical
Amylases hydrolyze a-14 linkages
Diagram courtesy
Langara College
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Amylopectin
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Mostly a-14 linkages; 4% a-16
Each sidechain has 15-25 glucose
moieties
a-16 linkages broken down by
debranching enzymes
300-6000 total glucose units per
amylopectin molecule
One reducing end, many nonreducing
ends
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Glycogen
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Principal storage form of glucose in
human liver; some in muscle
Branched (a-14 + a few a-16)
More branches (~10%)
Larger than starch: 50000 glucose
One reducing end, many nonreducing
ends
Broken down to G-1-P units
Built up from
G-6-P  G-1-P  UDP-Glucose units
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Glycogen
structure
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Biochem: Carbohydrates II
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Structural polysaccharides I
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Insoluble compounds designed to
provide strength and rigidity
Cellulose: glucose b-14 linkages
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Rigid, flat structure: each glucose is upside
down relative to its nearest neighbors
(fig.7.27)
300-15000 glucose units
Found in plant cell walls
Resistant to most glucosidases
Cellulases found in termites,
ruminant gut bacteria
Chitin: GlcNAc b-14 linkages:
exoskeletons, cell walls (fig. 7.26)
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Structural polysaccharides II
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Alginates: poly(b-D-mannuronate),
poly(a-L-guluronate), linked 14
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Agarose: alternating D-gal, 3,6-anhydro-L-gal,
with 6-methyl-D-gal side chains
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Cellulose-like structure when free
Complexed to metal ions:
3-fold helix (“egg-carton”)
Forms gels that hold huge amounts of H2O
Can be processed to use in the lab for gel exclusion
chromatography
Glycosaminoglycans: see next section
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Glycoconjugates
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Poly or oligosaccharides
covalently linked
to proteins or peptides
Generally heteroglycans
Categories:
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Image courtesy
Benzon Symposia
Proteoglycans
(protein+glycosaminoglycans)
Peptidoglycans (peptide+polysaccharide)
Glycoproteins (protein+oligosaccharide)
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Proteoglycans:
Glycosaminoglycans
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Unbranched heteroglycans of repeating
disaccharides
One component is
GalN, GlcN, GalNAc, or GlcNAc
Other component: an alduronic acid
—OH or —NH2 often sulfated
Found in cartilage, joint fluid
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Proteoglycans
in cartilage
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Highly hydrated,
voluminous
Mesh structure
(fig.7.36 or this fig.
from Mathews & Van
Holde)
Aggrecan is major
proteoglycan
Typical of
proteoglycans in that
it’s extracellular
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Biochem: Carbohydrates II
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Peptidoglycans
(G&G fig. 7.29)
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Polysaccharides linked to small proteins
Featured in bacterial cell walls:
alternating GlcNAc + MurNAc
linked with b-(14) linkages
Lysozyme hydrolyzes these polysaccharides
Peptide is species-specific:
often contains D-amino acids
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Peptidoglycans
in bacteria
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Gram-negative: thin peptidoglycan layer
separates two phospholipid bilayer
membranes
Gram-positive: only one bilayer, with thicker
peptidoglycan cell wall outside it
Gram stain binds to thick wall, not thin layer
Fig. 7.30 shows multidimensionality of these
walls
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Biochem: Carbohydrates II
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Peptide component
(G&G fig. 7.29)
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Sugars are crosslinked with entities
containing
(L-ala)-(isoglutamate)-(L-Lys)-(D-ala)
Gram-neg: L-Lys crosslinks via D-ala
Gram-pos: L-lys crosslinks via
pentaglycine followed by D-ala
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Biochem: Carbohydrates II
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Gram-negative bacteria:
the periplasmic space
(G&G fig. 7.30b, 7.31)
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Periplasmic space: space inside cell membrane
but inside just-described peptidoglycan layer
(note error in fig. legend!)
Peptidoglycan is attached to outer membrane
via 57-residue hydrophobic proteins
Outer membrane has a set of
lipopolysaccharides attached to it; these sway
outward from the membrane
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Biochem: Carbohydrates II
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Gram-negative membranes
and periplasmic space
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Figure courtesy
Kenyon College
microbiology
Wiki
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Biochem: Carbohydrates II
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Glycoproteins
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1-30 carbohydrate moieties per protein
Proteins can be enzymes, hormones,
structural proteins, transport proteins
Microheterogeneity:
same protein, different sugar
combinations
Eight sugars common in eukaryotes
PTM glycosylation much more common
in eukaryotes than prokaryotes
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Biochem: Carbohydrates II
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Diversity in glycoproteins
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Variety of sugar monomers
a or b glycosidic linkages
Linkages always at C-1 on one sugar but can
be C-2,3,4,6 on the other one
Up to 4 branches
But:
not all the specific glycosyltransferases you
would need to get all this diversity exist in any
one organism
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Biochem: Carbohydrates II
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O-linked and Nlinked
oligosaccharides
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Characteristic
sugar moieties
and attachment
chemistries
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Biochem: Carbohydrates II
p. 54 of 58
O-linked oligosaccharides
(fig. fig 7.32a, 7.33 in G&G)
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GalNAc to ser or thr;
often with Gal or Sialic acid on GalNAc
5-hydroxylysines on collagen are joined
to D-Gal
Some proteoglycans joined via
Gal-Gal-Xyl-ser
Single GlcNAc on ser or thr
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Biochem: Carbohydrates II
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N-linked
oligosaccharides
(fig. 7.32b,c in G&G)
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Generally linked to Asn
Types:
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High-mannose
Complex
(Sialic acid, …)
Hybrid
(Gal, GalNAc, Man)
09/22/2009
Biochem: Carbohydrates II
Diagram courtesy
Oregon State U.
p. 56 of 58
iClicker question 4
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Suppose you isolate a polysaccharide
with 5000 glucose units, and 3% of the
linkages are 1,6 crosslinks. This is:
(a) amylose
(b) amylopectin
(c) glycogen
(d) chitin
(e) none of the above.
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Biochem: Carbohydrates II
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iClicker question 5
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Suppose you isolate an enzyme that
breaks down b-1,4-glycosidic linkages
between GlcNAc units. This would act
upon:
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(a) glycogen
(b) cellulose
(c) chitin
(d) all of the above
(e) none of the above.
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