2. CHAPTER 7
Carbohydrates and Glycobiology
▫ Structures and names of monosaccharides
▫ Open-chain and ring forms of monosaccharides
▫ Structures and properties of disaccharides
▫ Biological function of polysaccharides
▫ Biological function of glycoconjugates
Key topics about carbohydrates:
3. Carbohydrates
• Named so because many have formula Cn(H2O)n
• Produced from CO2 and H2O via photosynthesis in plants
• Range from as small as glyceraldehyde (Mw = 90 g/mol)
to as large as amylopectin (Mw = 200,000,000 g/mol)
• Fulfill a variety of functions including:
▫ energy source and energy storage
▫ structural component of cell walls and exoskeletons
▫ informational molecules in cell-cell signaling
• Can be covalently linked with proteins to form
glycoproteins and proteoglycans
4. Carbohydrate Basics
• Carbohydrates are poly-hydroxy aldehydes or
polyhydroxy ketones
• The basic unit is a sugar molecule
▫ Also known as a saccharide
• Monosaccharide = single sugar unit
• Disaccharide = two sugar units, covalently bound
• Oligosaccharide = short chains of sugars
• Polysaccharide = >20 sugar units
5. Monosaccharides
• Single sugar unit
• The most common biological
monosaccharide: D-glucose
(dextrose)
• Most biologically relevant
monosaccharides have 3-6
carbons
• >4 C can readily form cyclic
structures
• Each monosaccharide—in its
linear form—contains one
carbonyl (C=O)
▫ rest of the Cs are bound to OH
groups
Drawing convention:
in the Fischer projection,
always put C=O towards
the top
6. Naming monomeric sugars
• All mono- and disaccharide names end in “-ose”
• Typical naming will include the number of
carbon atoms in the sugar molecule
▫ 3=triose
▫ 4=tetrose
▫ 5=pentose
▫ 6=hexose
▫ Rare examples of heptoses, octoses & nonoses in
biology
• Carbohydrates, especially simple ones, will often
have common names
7. Aldose v. Ketose
• Monosaccharides can be further subdivided into
aldoses and ketoses
• If the last carbon in the chain is the carbonyl,
this is an aldose
• Ketoses have the carbonyl anywhere else
OTHER than the final position
8. Aldoses and Ketoses
• An aldose contains an aldehyde functionality
• A ketose contains a ketone functionality
Carbonyl: C=O
9.
10. Sugars are CHIRAL
• Chirality adds more
structural diversity
and another level of
nomenclature
• Most carbons in a
sugar are chiral
• Aldoses naturally
have—on average—
more chiral centers
than ketoses
11. Glyceraldehyde
• Glyceraldehyde is a simple 3-carbon sugar
• The central C is chiral
• This is the standard by which the
configurational stereochemistry of D & L are set
for other sugars (and amino acids)…
12. Sugar Chirality
• With the vast number of multi-carbon sugars, we
need a simple way of diagramming them
• Fischer projections use the D- & L- representations
of glyceraldehyde to name sugars
13. Drawing Fisher projections
• Simpler than using perspective formulae
▫ chiral carbohydrates are commonly represented by
Fischer projections
• Horizontal bonds are pointing toward you
• Vertical bonds are projecting away from you
14. Sugar Chirality
• Compare the stereochemistry of the chiral center
most distant from the carbonyl to D and L
glyceraldehyde
• D-sugars will be drawn with the hydroxyl on the
RIGHT of the reference carbon, whereas L-sugars
will have the reference hydroxyl on the LEFT
15. Which one is D? Which one is L?
D-Ribose L-Ribose
16. Stereoisomers and Epimers
• Longer sugars allow for chemically identical yet
stereochemically different molecules
• Sugars that differ only in the stereochemistry of
ONE chiral center are called epimers
• Enantiomers
▫ Stereoisomers that are nonsuperimposable mirror
images
• Diastereomers
▫ stereoisomers not related through a reflection
operation
17.
18. Diastereomers
• Diastereomers:
stereoisomers that are
not mirror images
• Diastereomers have
different
physiochemical
properties
Boiling points of threose
(290.6 °C) & erythrose
(311.11 °C) are different
19. Epimers
• Epimers are two sugars that differ only in the
configuration around one carbon atom
20. Use of common names
• Carbohydrates, due to multiple stereocenters, can
have complex IUPAC names
▫ D-(−)-Erythrose = (2R,3R)-2,3,4-Trihydroxybutanal
▫ D-(−)-Threose = (2S,3R)-2,3,4-Trihydroxybutanal
Common names always refer to same
stereochemistry, so serve as useful
shorthand.
How many common names would you
need to cover all aldopentoses?
23. Sugars are also cyclic
• Most common 5-C & 6-C sugars
adopt a cyclic structure in
solution
• This occurs most commonly via
the reaction of the alcohol on
C5 with the aldehyde (aldoses)
or ketone (ketoses) on the
carbonyl carbon
• The cyclization results in
hemiacetals or hemiketals
24. Hemiacetals and Hemiketals
• Aldehyde and ketone carbons are electrophilic
• Alcohol oxygen atom is nucleophilic
• When aldehydes are attacked by alcohols, hemiacetals form
• When ketones are attacked by alcohols, hemiketals form
25.
26. Cyclization of monosaccharides
• Pentoses and hexoses readily undergo intramolecular cyclization
• The former carbonyl carbon becomes a new chiral center, called
the anomeric carbon
• The former carbonyl oxygen becomes a hydroxyl group; the
position of this group determines if the anomer is or
• If the anomeric OH group is on the opposite side (trans) of the
ring as the CH2OH moiety the configuration is
This is functionally equivalent to the anomeric OH cis to the reacting OH
group—best visualized in the Fischer projection
• If the hydroxyl group is on the same side (cis) of the ring as the
CH2OH moiety, the configuration is
This is functionally equivalent to the anomeric OH trans to the reacting OH
group—best visualized in the Fischer projection
27. Cyclic Sugars
• Cyclization of sugar monomers
introduces another source of
variability
• Monosaccharides that differ
only in the stereochemistry
around anomeric carbon,
as hemi-acetals or hemi-
ketals, are called anomers
29. Pyranoses and furanoses
• Aldohexoses can form 5- or
6-membered rings
• Five membered rings are
furanoses, named after the
similarity to furan
• Six membered rings are
pyranoses, named after the
similarity to pyran
30. Haworth Perspective Formulae
• Haworth perspectives depict
cyclic sugars
• Lines drawn up from the
carbon indicate the H or OH
is above the plane of the ring
31. Rings, chairs and boats
• Ring structures of monosaccharides in solution are not
actually planar
• Most monosaccharides form chair structures
▫ Conformational isomers or conformers
▫ Chair conformation review
• Which of the 2 chair structures is predominant depends
on the steric hindrance of the groups on the sugar—axial
vs. equatorial groups
33. β is preferred over α→
Quick mini-quiz:
• What makes these
α or β?
• Why is the β form
here “preferred”?
~46 kJ required for
transition
34. Carbohydrates in solution reach
equilibrium
• The stability of each structural variation of a
given sugar molecule determines its equilibrium
population
• A solution of glucose will reach an equilibrium:
▫ ~36% α-D-glucopyranose
▫ ~64% β-D-glucopyranose
▫ Trace linear
▫ Trace glucofuranose
α-D-glucofuranose
35. Chain-Ring Equilibrium & Reducing Sugars
• Ring forms exist in equilibrium with the open-chain
form. All monosaccharides are thus reducing sugars
• Aldehydes can reduce Cu2+ to Cu+ (Fehling’s test)↓
• Aldehydes can reduce Ag+ to Ag0 (Tollens’ test)
• This allows detection of reducing sugars, such as
glucose
36. Substituted Rings
• The most common class of biological
monosaccharides are the hexoses
• Hexoses are often substituted at one or more of
the carbon atoms
• Deoxy sugars are the most common substituted
groups
▫ one hydroxyl is converted to a H
39. Disaccharides
• Disaccharides are 2
monosaccharides joined by a
covalent linkage known as the
O-glycosidic bond
• Two sugar molecules are joined
between an anomeric carbon
and a hydroxyl carbon
40. The Glycosidic Bond
• The glycosidic bond (an acetal) between monomers
is now relatively unreactive compared to the
hemiacetal at the second monomer
▫ 2nd monomer, often contains hemiacetal, is reducing
▫ 1st monomer: anomeric carbon is involved in the glycosidic
linkage, thus it’s is nonreducing
• The disaccharide formed upon condensation of two
glucose molecules via 1 4 bond is called maltose
42. Naming Disaccharides
1. Name the configuration (/) of the
anomeric carbon of the first sugar
2. Add -pyranosyl or -furanosyl to
distinguish 6- from 5-membered rings,
respectively
3. Indicate the 2 carbon atoms joined via
the glycosidic bond in parentheses
If the two anomeric carbons are linked,
specify the α/β confirmations of each
4. Name the second residue using the
same -pyranose or -furanose
designation system
5. Repeat the process if there is a 3rd sugar,
etc. Why isn’t there a β here?
43. Chain-Ring Equilibrium & Reducing disaccharides
• The anomeric carbon in the 1st saccharide is an
acetal or ketal, thus non-reducing
• If the 2nd anomeric carbon is free, it can still
linearize into an aldehyde or ketone
Benedict’s Reagent test
44. Nonreducing Disaccharides
• Two sugar molecules can be joined via a glycosidic
bond between two anomeric carbons
• The product has two acetal/ketal groups and no
hemiacetals/hemiketals
• Thus, there are no reducing ends: this is a
nonreducing sugar
45. Polysaccharides
• Polysaccharides are long
sugar polymers
• Homopolysaccharides
▫ all one type of
monosaccharide
• Heteropolysaccharides
▫ different monosaccharides
• Polysaccharides can be
linear or branched
• Different structural &
storage roles…
46. 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
47. 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
49. Polymeric glucose
• Single glycogen
molecule has 1
reducing end & many
non-reducing ends
• Advantages?
Why not store glucose in monomeric form?
• 0.01 μM glycogen can break up into 0.4M glucose
• Consider the consequences of 0.4M glucose inside a cell
•Osmolarity
•Transport
51. Metabolism of Glycogen and Starch
• Glycogen and starch often form
granules in cells
• Granules contain enzymes that
synthesize and degrade these
polymers
• Glycogen and amylopectin have
one reducing end but many
nonreducing ends
• Enzymatic processing occurs
simultaneously @ many
nonreducing ends to release
glucose
52. Structural Polysaccharides
• Cellulose is a structural
component of plants
▫ Also composed of amylose and
amylopectin, but the linkages
are β, not α
• Chitin is a homopolymer of N-
acetylglucosamine (GlcNac) in
β linkages
▫ Found in the exoskeletons of
insects
53. • Cellulose is a branched homopolysaccharide of glucose
▫ Glucose monomers form (1 4) linked chains
▫ Hydrogen bonds form between adjacent monomers
▫ Additional H-bonds between chains
▫ Structure is now tough and water-insoluble
▫ Most abundant polysaccharide in nature
▫ Cotton is nearly pure fibrous cellulose
54. Cellulose Metabolism
• The fibrous structure and water-insolubility make cellulose a
difficult substrate on which to act
• Fungi, bacteria, and protozoa secrete cellulase, which allows
them to use wood as source of glucose
▫ Most animals cannot use cellulose as a fuel source because they
lack enzymes to hydrolyze (1 4) linkages
• Ruminants and termites live symbiotically with
microorganisms that produces cellulase
• Cellulases hold promise in the fermentation of biomass into
biofuels
55. Chitin
• Chitin is a linear homopolysaccharide of N-acetylglucosamine
– N-acetylglucosamine monomers form (1 4)-linked chains
– Forms extended fibers that are similar to those of cellulose
– Hard, insoluble, cannot be digested by vertebrates
– Structure is tough but flexible, and water-insoluble
– Found in cell walls in mushrooms, and in exoskeletons of insects, spiders,
crabs, and other arthropods
56. Polysaccharides have higher order
structures
• Disaccharides can rotate around the glycosidic
bonds
• The monosaccharide rings act as “planes” that
rotate around the point of the glycosidic oxygen
• Therefore they have f & y angles
• Hydrogen bonding between residues is also
important for the structural integrity of a
polysaccharide.
57. α vs. β linkages
• Structural polysaccharides often utilize β linkages rather
than α.
• In amylose—with its (α1→4) glucose linkages—the most
stable configuration is a 60°bend between the planes
• This limits H-
bond availability
between sugar
residues &
promotes loose
helical structure
58. • In cellulose—with its (β1→4) glucose linkages—the most
stable configuration is a 180°bend between the planes
• This readily allows H-bonds to form between monomers
& across strands
α vs. β linkages
60. Agar and Agarose
• Agar is a complex mixture of hetereopolysaccharides
containing modified galactose unitsthat serves as a cell wall
component of some algaes & seaweeds
▫ ~70% Agarose
▫ ~30% Agaropectin
61. Agarose gels are useful in
separating nucleic acids
…and in growing microbial
cultures ↓
62. Polysaccharides in cell walls
• The cell walls of bacteria are made up of crosslinked
hetero-polysaccharides
• Peptidoglycan is made of strands of alternating
N-acetylglucosamine (GlcNac) 1→4 N-acetylmruanic
acid (MurNac)
▫ Crosslinked to protein scaffold via MurNac residues
• Gives the cells structure and resistance to osmotic
rupture
65. Peptidoglycan
• Peptidoglycan is vulnerable to the enzyme lysozyme
▫ Found in tears
• Antibiotics often work by preventing the proper formation
of these cell walls
▫ Penicillin prevents synthesis of the crosslinks
66. Glycoconjugates
• Many proteins and lipids have
mono- or polysaccharides
attached to them
• Glycoproteins – found in the
cell membrane, secreted from
cells, and inside organelles in the
secretory pathway
• Proteoglycans – found in the
cell membrane & extracellular
matrix
• Glycolipids – found in the outer
leaflet of the cell membrane.
Serve as receptors for certain
extracellular proteins
67. Extracellular Matrix
• The extracellular matrix
is the mesh between
cells
▫ Allows for passage of
materials but also
provides structural
support and cushioning
• Glycosaminoglycans:
heteropolysaccharides
found in the ECM along
with fibrous proteins
68. Glycosaminoglycans
• Linear polymers of repeating disaccharide units
• One monomer is an amino sugar
▫ N-acetyl-glucosamine (GlcNac)
▫ N-acetyl-galactosamine (GalNac)
• Other monomer is typically:
▫ Uronic acid (C6 oxidation)
▫ Galactose
• Extended highly hydrated molecule
▫ Minimizes charge repulsion
• Forms meshwork with fibrous proteins to form extracellular
matrix
▫ Connective tissue
▫ Lubrication of joints
69. Glycosaminoglycans
• Most are proteoglycans
(linked to proteins)
Examples:
• Hyaluronic acid: long polysaccharide
involved in lubricating joints
• Chondroitin sulfate: structural
component of cartilage
• Keratan sulfate: found in cornea,
cartilage, & bone
• Heparin: naturally occurring
anticlotting agent, used as medication
70. Proteoglycan Aggregates
• Hyaluronan and aggrecan
form huge (Mr > 2 108)
noncovalent aggregates
• Hold lots of water (1000
its weight) & provides
lubrication
• Very low friction material
• Covers joint surfaces:
articular cartilage
▫ Reduced friction
▫ Load balancing
71. Glycoconjugates: Glycoprotein
• A protein with relatively 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 are heavily glycosylated; helps evade the
immune system
72. Glycoproteins vs. proteoglycans
• Glycoproteins are proteins with carbohydrate
groups
• Proteoglycans are glycoproteins that are so
heavily glycosylated that carbohydrates
dominate the molecular weight and the
physiological functions, reflected in the
nomenclature
74. Why glycosylate proteins?
• Not completely sure in many cases…
• Many cellular processes are seemingly
unaffected by a complete block of glycosylation
• May play a role in protein solubility or folding
• Cell-cell adhesion controlled by sugar-binding
proteins called lectins
75. Why glycosylate proteins?
• ~50% of all human proteins are glycosylated
▫ So it must be important, right?
• Improperly glycosylated proteins are degraded
rather rapidly
▫ Perhaps a sign of protein “health”?
76. Glycosylation = Outside
• Only proteins that are outside the cell are
glycosylated
• Glycophorin A (GpA) is a membrane protein in
erythrocytes with >60% of its mass coming from
glycosylations
▫ gives cells very hydrophilic/charged coat, reducing
adhesion
• GpA is essentially one TM domain with the
extracellular domain highly glycosylated
77. Glycophorin A
• Extremely well-studied
• Forms tight TM-dimers
• Dimerization driven by
VDW-packing in the
membrane
78. Glycosylation = Outside
• Secreted proteins also have glycosylations
• Antibodies, hormones, and many signaling
proteins have glycosylations
• Some signaling molecules have different
glycosylation patterns depending on which
tissue they are found in
79. Glycolipids
• A lipid with covalently bound
oligosaccharide
▫ Parts of plant and animal cell
membranes
▫ In vertebrates, ganglioside
carbohydrate composition
determines blood groups
▫ In gram-negative bacteria,
lipopolysaccharides cover the
peptidoglycan layer
• Only found in the outer-leaflet
of the cell membrane
• Linked to the headgroup of
lipid molecules
Bacterial lipopolysaccharide
80. Lipopolysaccharide (LPS)
• Major component of gram negative bacterial outer membranes
• LPS has a core region and an O-specific region that differ from
bacterial strain to strain
• Very immunoreactive!
81. Sugars = Complex Information
• Diversity in sugar structure allows for increased
combinatorial possibilities
• The ability to form O-glycosidic bonds at
multiple positions on the sugar ring increases
combinations exponentially
• Allows for very specific structural information
storage—proteins can “read” surface
carbohydrates and act
82. Lectins
• Lectins = proteins that bind carbohydrates with
high affinity
• Many hormones and signaling molecules are
glycosylated. Having high affinity binding
allows for quick responses to small
concentrations
83. Selectins
• Membrane proteins
lining vasculature are
expressed in differing
patterns in response to
inflammation
• Selectins bind to
glycosylated proteins on
T-cells circulating in the
vessel
• This allows for a second
interaction between
epithelial integrins
and the T-cell
84. Bacterial Toxins and Viruses
• Many bacterial toxins are also lectins
• Cholera and Ricin toxins bind gangliosides (see
textbook) as the cellular receptor
• A variety of viruses also use binding to
glycosylations on cell surface proteins as the
target
85. Study Questions
• Due next regular lecture
Draw & name the cyclic structures of the following:
1. D-Sorbose (can make pyranose & furanose
forms)
2. L-Gulose (pyranose)
3. L-Ribose (furanose)
4. D-Altrose (pyranose)
86. Study Questions
Draw & name the structures of the following:
5. Draw & name the result of a β2→4 bond
between β-D-Sorbose & β-L-Gulose
6. Draw & name the result of an α1→ α1 bond
between α-L-Ribose & α-D-Altrose
7. Can these two disaccharides react to form a
tetrasaccharide? If not, why? If so, what are the
possible reaction routes?