Carbohydrates II
Andy Howard
Introductory Biochemistry, Fall 2010
16 September 2010
Biochem: Carbohydrates II
09/16/2010
Mono-, oligo- and
polysaccharides

These are the most abundant organic
molecules on the planet, and they act as
metabolites, components of complexes,
and structural entities
09/16/2010
Biochem: Carbohydrates II
p. 2 of 48
What we’ll discuss




Details of
monosaccharide
nomenclature
Cyclic sugars
Sugar derivatives
Glycosides
09/16/2010

Polysaccharides



Starch & glycogen
Cellulose & chitin
Glycoconjugates



Biochem: Carbohydrates II
Proteoglycans
Peptidoglycans
Glycoproteins
p. 3 of 48
Monosaccharide structures



Remember that there is just one 3carbon ketose and two 3-carbon aldoses
Addition of each –CHOH group gives us
one more chiral center
Unique names for each enantiomorphic
monosaccharide
09/16/2010
Biochem: Carbohydrates II
p. 4 of 48
Properties



Enantiomers have identical physical
properties (MP,BP, solubility, surface
tension…) except when they interact with
other chiral molecules
(Note!: water isn’t chiral!)
Stereoisomers that aren’t enantiomers
can have different properties; therefore,
they’re often given different names
09/16/2010
Biochem: Carbohydrates II
p. 5 of 48
Sugar nomenclature


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
09/16/2010
Biochem: Carbohydrates II
p. 6 of 48
Fischer projections



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.
09/16/2010
Biochem: Carbohydrates II
Emil
Fischer
p. 7 of 48
D-aldose family tree
09/16/2010
Biochem: Carbohydrates II
p. 8 of 48
D-ketose family tree
09/16/2010
Biochem: Carbohydrates II
p. 9 of 48
How many of these
are important?




D-sugars are more prevalent than Lsugars
3-, 5-, and 6-carbon sugars are the most
important, but 4’s and 7’s play roles
Some 5’s and 6’s are obscure
Glucose, ribose, fructose, glyceraldehyde
play more important roles than the others
09/16/2010
Biochem: Carbohydrates II
p. 10 of 48
Cyclic sugars


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
09/16/2010
Biochem: Carbohydrates II
p. 11 of 48
Hemiacetals & hemiketals


Hemiacetals and hemiketals are
compounds that have an –OH and
an –OR group on the same carbon
Cyclic monosaccharides are
hemiacetals & hemiketals
09/16/2010
Biochem: Carbohydrates II
p. 12 of 48
How do we cyclize a sugar?




Formation of an internal hemiacetal or
hemiketal (see previous slide) 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
Very low energy barriers between openchain form and various cyclic forms
09/16/2010
Biochem: Carbohydrates II
p. 13 of 48
Furanoses



Formally derived from
structure of furan
Hydroxyls hang off of the
ring; stereochemistry
preserved there
Extra carbons come off at 2
and 5 positions
09/16/2010
Biochem: Carbohydrates II
1
5
2
4
3
furan
p. 14 of 48
1
Pyranoses
6



Formally derived from
structure of pyran
Hydroxyls hang off of the
ring; stereochemistry
preserved there
Extra carbons come off at 2
and 6 positions
09/16/2010
Biochem: Carbohydrates II
2
3
5
4
pyran
p. 15 of 48
Haworth projections

…provide a way of
keeping track the chiral
centers in a cyclic sugar,
as the Fischer
projections enable for
straight-chain sugars
09/16/2010
Biochem: Carbohydrates II
Sir Walter
Haworth
p. 16 of 48
O
The anomeric carbon


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
09/16/2010
Biochem: Carbohydrates II
O
p. 17 of 48
iClicker quiz, question 1

Which of these is a furanose sugar?
09/16/2010
Biochem: Carbohydrates II
p. 18 of 48
iClicker quiz, question 2






Which carbon is the anomeric
carbon in this sugar?
(a) 1
(b) 2
(c) 5
(d) 6
(e) none of these.
09/16/2010
Biochem: Carbohydrates II
p. 19 of 48
iClicker, question 3






How many 7-carbon D-ketoses are
there?
(a) none.
(b) 4
(c) 8
(d) 16
(e) 32
09/16/2010
Biochem: Carbohydrates II
p. 20 of 48
a-Dglucopyranose


One of 2 possible
pyranose forms of Dglucose
There are two
because the anomeric
carbon itself becomes
chiral when we
cyclize
09/16/2010
Biochem: Carbohydrates II
p. 21 of 48
b-Dglucopyranose

Differs from aD-glucopyranose only
at anomeric
carbon
09/16/2010
Biochem: Carbohydrates II
p. 22 of 48
Count carefully!





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
09/16/2010
Biochem: Carbohydrates II
p. 23 of 48
Substituted monosaccharides



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
HO
O
GlcNAc HNCOCH
OH
3
09/16/2010
HO
D-glucuronic acid
HO
(GlcUA)
Biochem: Carbohydrates II
O
OH
p. 24 of 48
6
Sugar acids
(fig. 7.10)

Gluconic acid:





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
09/16/2010
Biochem: Carbohydrates II
p. 25 of 48
Sugar alcohols (fig.7.11)





Mild reduction of sugars convert aldehyde
moiety to alcohol
Generates an additional asymmetric
center in ketoses
These remain in open-chain forms
Smallest: glycerol
Sorbitol, myo-inositol, ribitol are important
09/16/2010
Biochem: Carbohydrates II
p. 26 of 48
Sugar esters
(fig. 7.13)


Phosphate esters of
sugars are significant
metabolic intermediates
5’ position on ribose is
phosphorylated in
nucleotides
09/16/2010
Biochem: Carbohydrates II
Glucose 6phosphate
p. 27 of 48
OH
Amino sugars
HO
HO
GlcNAc



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
09/16/2010
Biochem: Carbohydrates II
p. 28 of 48
Acetals and ketals


Acetals and ketals have two —OR groups on a
single carbon
Acetals and ketals are found in glycosidic bonds
09/16/2010
Biochem: Carbohydrates II
p. 29 of 48
Oligosaccharides and other
glycosides


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
09/16/2010
Biochem: Carbohydrates II
p. 30 of 48
Sucrose: a glycoside


A disaccharide
Linkage is between
anomeric carbons of
contributing
monosaccharides,
which are glucose
and fructose
09/16/2010
Biochem: Carbohydrates II
p. 31 of 48
Other disaccharides

Maltose



Cellobiose



a-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


Milk sugar
Lactose intolerance caused by absence of
enzyme capable of hydrolyzing this glycoside
09/16/2010
Biochem: Carbohydrates II
p. 32 of 48
Reducing sugars




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
09/16/2010
Biochem: Carbohydrates II
p. 33 of 48
Ketoses are reducing sugars

In presence of base a ketose can
spontaneously rearrange to an aldose
via an enediol intermediate, and then
the aldose can be oxidized.
09/16/2010
Biochem: Carbohydrates II
p. 34 of 48
Sucrose: not a reducing sugar


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
09/16/2010
Biochem: Carbohydrates II
p. 35 of 48
Reducing & nonreducing ends




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
09/16/2010
Biochem: Carbohydrates II
p. 36 of 48
Why does this matter?


Partly historical: this cuprate reaction was
one of the first well-characterized tools
for characterizing these otherwise very
similar compounds
But it also gives us a convenient way of
distinguishing among types of glycosidic
arrangements, even if we never really
use Cu2+ ions in experiments
09/16/2010
Biochem: Carbohydrates II
p. 37 of 48
Glycosides



Glycosides are covalent conjugates of a
sugar with another species
Generally involve replacement of a sugar
–OH group with a moiety that begins with
an oxygen or a nitrogen
We describe them as N-linked and Olinked glycosides
09/16/2010
Biochem: Carbohydrates II
p. 38 of 48
Nucleosides



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
09/16/2010
Biochem: Carbohydrates II
Diagram courtesy of
World of Molecules
p. 39 of 48
Polysaccharides



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
09/16/2010
Biochem: Carbohydrates II
p. 40 of 48
Categories of polysaccharides

Storage homoglycans (all Glc)



Structural homoglycans



Starch: amylose (a(14)Glc) , amylopectin
Glycogen
Cellulose (b(14)Glc)
Chitin (b(14)GlcNac)
Heteroglycans


Glycosaminoglycans (disacch.units)
Hyaluronic acid (GlcUA,GlcNAc)(b(1  3,4))
09/16/2010
Biochem: Carbohydrates II
p. 41 of 48
Storage polysaccharides


Available sources of glucose for energy
and carbon
Long-chain polymers of glucose



Starch (amylose and amylopectin):
in plants, it’s stored in 3-100 µm granules
Glycogen
Branches found in all but amylose
09/16/2010
Biochem: Carbohydrates II
p. 42 of 48
Amylose




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
09/16/2010
Biochem: Carbohydrates II
p. 43 of 48
Amylopectin





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
09/16/2010
Biochem: Carbohydrates II
p. 44 of 48
Glycogen







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
09/16/2010
Biochem: Carbohydrates II
p. 45 of 48
Glycogen
structure
09/16/2010
Biochem: Carbohydrates II
p. 46 of 48
Structural polysaccharides I


Insoluble compounds designed to
provide strength and rigidity
Cellulose: glucose b-14 linkages






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)
09/16/2010
Biochem: Carbohydrates II
p. 47 of 48
Structural polysaccharides II

Alginates: poly(b-D-mannuronate),
poly(a-L-guluronate), linked 14



Agarose: alternating D-gal, 3,6-anhydro-L-gal,
with 6-methyl-D-gal side chains



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
09/16/2010
Biochem: Carbohydrates II
p. 48 of 48