Heparin

Cellulose fibers

Sugar
 Carbohydrates
Monosaccharides and polysaccharides
•  Energy source
Biological Functions

–  Starch, glycogen, sucrose

•  Structural Material
–  Cellulose
•  Structural elements of nucleic acids
–  Ribose, deoxyribose
•  Signaling
–  Cell-receptors
 Monosaccharides
Simple Sugars
Polyhydroxy Alcohols

Aldehyde or ketone derivatives of straight-chain polyhydroxy

alcohols containing at least three carbon atoms.

Aldoses
²  The carbonyl group is an
aldehyde.
²  The smallest, with 3 C
atoms, are aldotriose.
²  (CŸH2O)n
²  Aldohexoses,i.e. glucose.
Ketoses
²  The carbonyl group is a
ketone.
²  The smallest, with 3 C
atoms, are trioses.
²  (CŸH2O)n
²  Hexoses, i.e. fructose.

Classified based on the chemical nature of the carbonyl

group, and # of C atoms.
 Monosaccharides
Simple Sugars
Polyhydroxy Alcohols

Aldoses Ketoses
The arrows show
stereochemical
relationships
 Aldoses
The carbonyl group is an aldehyde.

Aldotriose

* Aldotetroses *

D sugars have the same absolute configuration at the asymmetric

center farthest from the carbonyl group as does D-glyceraldehyde.
 Fisher Projections

The carbonyl group is

an aldehyde.

D sugars are more

abundant
biologically than
L sugars. Hence,
the D prefix is
often omitted.
i.e. Glucose refers
to D-Glucose
Horizontal bonds project toward the viewer
Vertical bonds project away from the viewer
 Epimers
D-Gulose D-Idose
1CHO 1CHO

H * OH HO H
16 stereoisomers

H * OH H OH
HO * H HO H
H * OH H OH
6CH OH 6CH OH
2 2

(Differ only by the configuration around one C atom, epimers)

 Epimers
D-Glucose D-Mannose
1CHO 1CHO

H * OH HO H
16 stereoisomers

HO * H HO H
H * OH H OH
H * OH H OH
6CH OH 6CH OH
2 2

(Differ only by the configuration around one C atom, epimers)

(in aldoses) Cyclic Structures

H RO H
R OH2 R'
O R' OH
Hemiacetal
(in ketoses)

R'' RO R''
R OH2 R'
O R' OH

Hemiketal
 Cyclization of Fructose
Linear to Cyclic

1CH OH
2
O 6 1 6
CH2OH CH2OH CH2OH OH
HO H OH O
5 H OH 2 5 H OH 2
H OH O
H4 3 H4 3 CH2OH
H OH OH H OH H 1
6CH2OH
Haworth
Same projection
 Cyclization of Fructose
Linear to Cyclic

How to draw Haworth projection

H H OH
6 1
HOH2C CH2OH
OHOHH O
1CH OH
2 1CH OH
2
H H OH
O 6
HOH2C O
HO H OHOHH

H OH HOH2C OH
H
1
CH2OH
OH
6
H OH O
anomeric carbon H
H
6
1CH OH
H2OH CH 2OH
6 HO
2 CH2OH OH
OH O HOH2C OH 1
CH2OH
H OH 2 5 H OH 2 6
H OH
O H O
4 3 H4 3 CH2OH HO H
OH H OH H 1
Cyclic Structures

Pyran

Furan
Anomeric Forms (α, β) of Cyclic Sugars
D−Glucose
same
opposite
side
sides

anomeric
carbon
α−D−Glucopyranose β−D−Glucopyranose

36.4% 63.6%
 Glucose Conformations

Stable Less stable

Non-H substituents More crowded

occupy equatorial
positions.
 Modifications of Sugars
Covalent Linkages

Aldose Oxidation Oxidation of 1°−OH

of aldoses

Aldonic Acids Uranic Acids

 Modifications of Sugars
Covalent Linkages

Reduction under mind conditions to yield alditols

(i.e. in the presence of NaBH4)

Alditols are polyhydroxy alcohols.

 Modifications of Sugars
Covalent Linkages

An −OH is replaced by H known as deoxy sugars.

 Modifications of Sugars
Covalent Linkages

One or more −OH is replaced by −NH2

(−NH2 is often acetylated)
 Glycosidic Bond Likages via
Anomeric Carbon
Anomeric group condenses with an −OH to form
α− β−glycosides
 Glycosidic Bond Linkages via
Anomeric Carbon

Link D-ribose to purines

and pyrimidines in
nucleic acids.

Sugars are termed

“non-reducing” in the
presence of a glycosidic
bond. (Glycoside sugar)
Structures of Sugars you are expected
to remember and draw

D-Glyceraldehyde
Galactose
Ribose
Glucose (Glucopyranose)
Mannose
Dihydroxyacetone
Fructose (Fructofuranose)
Glycerol
 Polysaccharides (Glycans)

Consist of monosaccharaides linked together by

glycosidic bonds.

Homopolysaccharides:
Consist of a single type of monosaccharide.

Heteropolysaccharides:
More than one type of monosaccharide, yet most
contain only few types that alternate in a
repetitive sequence.
 Polysaccharides (Glycans)

The complete identity of an oligosaccharides,

the identities, anomeric forms, and linkages of
all its monosaccharides, can be determined:

Specific enzymes that hydrolyze the

monosaccharides:
Exoglycosidases
Endoglycosidases

Structure and conformations:

NMR spectroscopy
 Disaccharides

The simplest polysaccharides, and the most

common.
Many occur as the hydrolysis product of larger
molecules.
Lactose and sucrose are notable on their own.
 Lactose

Occurs naturally in milk, 0 to 7%.

Systematic name:
O−β−D−galactopyranosyl−(1à4)−D−glucopyranose

Monosaccharide
Ring type
Linkage

Lactose is a
reducing sugar
 Sucrose
The most abundant, and the major form in which
carbohydrates are transported in plants.
O−α−D−glucopyranosyl−(1à4)−β−D−fructofuranoside

Aspartame: a non-carbohydrate that mimics the

taste of sucrose.
 Cellulose and Chitin
Structural Polysaccharides
Cellulose is the primary structural component of
plant cell wall; a rigid cell wall that withstand
osmotic pressure differences up to 20 atm.
A linear polymer of D−glucose residues linked by
β(1à4) glycosidic bonds.
X-Ray: Flat ribbons
chains, successive
glucose rings are
turned over with
respect to each
other. C3−OH forms
H−bond with O5.
 Cellulose and Chitin
Structural Polysaccharides
Parallel cellulose chains from sheets that stack,
held together by hydrogen bonds and van der walls
interactions.

In plant cell wall, the cellulose fibers are embedded

in and cross-linked by a matrix containing other
polysaccharides and lignin.
It can withstand a lot of pressure, and can not be
easily converted to biofuels.
 Cellulose and Chitin
Structural Polysaccharides
Chitin is the principle structural component of the
exoskeleton of invertebrates and in the cell wall of
most fungi and many algae.

β(1à4) linkages.

Chemically, chitin
differs from
cellulose by an
acetamido
function.
 Starch and Glycogen
Storage Polysaccharides
Starch is a mixture of glycans, synthesized by
plants as energy reserve.
It is deposited in the chloroplasts of plant cells as
insoluble granules: α-amylose and amylopectin.

α(1à4) linkages.
An isomer of glucose
with very different
structural properties.
α(1à4) glycosidic β(1à4)
linkages cellulose
Tightly packed fully
extended
conformation

α-amylose
Irregularly aggregating
helically coiled
conformation
 Starch and Glycogen
Storage Polysaccharides

Amylopectin, 106
glucose molecules.

α(1à4) linkages,
with α(1à6) linkages
every 24 to 30
glucose residues.
 Starch and Glycogen
Storage Polysaccharides
Starch is a reducing sugar, has one residue lacking
a glycosidic bond, the reducing end.

The main carbohydrate sours in the human diet.

In the mouth, amylase, hydrolyzes the glycosidic
bonds of starch.
In the small intestine, pancreatic amylase,
degrades it into small oligosaccharides.
Further hydrolysis occurs by α-glucosidase, and
debranching enzymes.
 Starch and Glycogen
Storage Polysaccharides
Glycogen, storage molecule of animals, present
mainly in skeletal muscle and liver cells.
A highly branched structure with a primary
structure resembling that of amylopectin:
Branched molecule with α(1à4) linkages, with
α(1à6) linkages every 8 to 14 glucose residues.
 Starch and Glycogen
Storage Polysaccharides
Glycogen is degraded for metabolic use in the cell
by glycogen phosphorylase, which cleaves
glycogen’s α(1à4) bonds sequentially inward from
its nonreducing ends.
Its branched structure permits rapid mobilization
of glucose, due to the presence of many
nonreducing ends.
Glycogen debranching enzymes cleave the
α(1à6) branches of glycogen.
 Glycosaminoglycans
Collagen is found in extracellular spaces, particularly
those of connective tissues, i.e. blood vessel walls.

Collagen is also found in other proteins embedded in

a gel-like matrix, composed mainly of
glycosaminoglycans.

Its solution is slimy, mucus-like consistency, as a

result of its high viscosity and elasticity.
 Glycosaminoglycans
Hyaluronate: an important glycosaminoglycan
component of connective tissue, synovial fluid, and
vitreous humor of the eye.
It is composed of 250 to 25,000 β(1à4) linked
disaccharide units:
β(1à3)
Rigid extended
molecule.
In solution, ~1000
times its dry
volume.
 Glycosaminoglycans
Other common glycosaminoglycans consist of 50 to
1000 sulfated disaccharide units:

Derived by enzymatic epimerization of the C5 of glucuronate

residues.
 Glycosaminoglycans
Keratan sulfate is the most hetereogenoues of the
major glycosaminoglycans: its sulfur content is
variable, and it contains small amounts of fucose,
mannose, GlcNAc, and salisilic acid.
 Glycosaminoglycans
Heparin occurs almost exclusively in the intracellular
granules of the mast cells that occur in the arterial
walls.
It is variably sulfated, 2.5 sulfate residue/
disaccharide unit. Hence, it is the most highly
charged polymer in mammalian tissue.
 Glycosaminoglycans
Heparin inhibits blood clotting.
A helical polymer, with a repeat unit
every two disaccharides and a pitch
of 17.5 Å.
A high density of anionic sulfate
groups is observed, shown as yellow
sticks.
 Glycoproteins
Proteins linked to Sugars
•  Glycoproteins contain carbohydrate
–  1% to 90% by weight
•  Many functions
–  Enzymes, transport proteins, receptors, hormones,
and structural proteins.
•  Variable carbohydrate composition,
microheterogeneity
–  The carbohydrate chains are covalently linked to the
polypeptide.
 Proteoglycans

Proteoglycans are proteins and glycosaminoglycans,

present in the extracellular matrix, that aggregate
(non)covalently forming a diverse group of
macromolecules.
A “bottle like” molecular
architecture, with
“bristles” noncovalently
attached to a filamentous
hyaluronate.
Highly hydrated
complexes.
 Proteoglycans
The bristles consist of a core protein covalently linked
to glycosaminoglycans (most common keratan sulfate
and chondroitin sulfate) via the side chain O atoms of
specific Ser or Thr residues, O-linked oligosaccharides.
A link protein stabilizes the core protein and the
hyaluronate.
Smaller oligosaccharides
are glycosidically linked
to the core protein via
the amide N of specific
Asn residues, N-linked
oligosaccharides.
 Proteoglycans
Hyaluronate varies in length, 400 to 40,000 Å, with up
100 associated core proteins, each with ~ 50 keratan
sulfate chains and ~ 100 chondroitin sulfate chains.
Cartilage consist of a
meshwork of collagen
fibrils filled in by
proteoglycans.
 Bacterial Cell Walls
Bacteria are surrounded by rigid cell wall, which permits
them to live in a hypotonic environment.
Its cell wall is responsible for bacterial virulence.
Gram-positive or gram-negative.
 Bacterial Cell Walls
Think cell wall (~250 Å). Thin cell wall (~30 Å)
covered by a complex
outer membrane, which
exclude toxic substances
including.
 Bacterial Cell Walls
The cell wall consist of covalently linked polysaccharide
and polypeptide chains completely enclosing the cell, a
peptidoglycan.
Its polysaccharide component consists of linear chains of
alternating β (1à4) linked GlcNAc and N-acetylmuramic
acid.
 The lactic acid group of N-
acetylmuramic acid forms an amide
bond with a D-amino acid-containing
tetrapeptide to form the
peptidoglycan repeating unit.

Staphylococcus aureus bacterium.

Neighboring parallel peptidoglycan
chains are covalently cross-linked
(~40%) through their tetrapeptide side
chain.
The cross-link
consist of a
pentaglycine chain
extending from the
terminal carboxyl
group of one
tetrapeptide to the
ε-amino group of Lys
in the neighboring
tetrapeptide.

Staphylococcus aureus bacterium.

Simon Foster studied the bacterium
via atomic force microscopy (AMF).

The cell wall of the gram-negative

bacterium Bacillus subtilis containing
several glycan chains cross-linked to
form peptidoglycan “ropes”.

It consists of a right-handed helical

cable composed of several
peptidoglycan strands that wraps the
bacterium’s plasma membrane.

3 µm long
 Bacterial Cell Walls
The D-amino acids of peptidoglycans render them resistant
to proteases, which are mostly specific for L-amino acids.

Lysozyme, is an enzyme that catalyzes the hydrolysis of

the β (1à4) linked N-acetylmuramic acid and
N-acetylglucosamine.
 Glycosylated Eukaryotic Proteins
Oligosaccharides are covalently attached to proteins by
either N-glycosidic or O-glycosidic bonds.
In N-linked oligosaccharide, GlcNAc is β-linked to the
amide nitrogen of an asparagine residue in the sequence
Asn−X−Ser or Asn−X−Thr, where X ≠ Pro.
N-glycosylation occurs cotranslationally.
Synthesis of N-linked oligosaccharides
 Glycosylated Eukaryotic Proteins
The exact steps of N-linked oligosaccharide processing vary
with the identity of the glycoprotein and the present
endoglycosidases in the cell.
All have a common core pentasaccharide:

Processing is limited in some glycoproteins leaving high-

mannose oligosaccharides. Extensive process generate
large oligosaccharides with several kinds of sugar residues.
 Glycosylated Eukaryotic Proteins
In O-linked oligosaccharide, the most common O-glycosidic
attachment involves the disaccharide core β−galactosyl
−(1à3)−α−N-acetylgalactosamine linked to the OH group of
either Ser or Thr residue.
Vary in size from single galactose residue inn collagen to
chains with up to 1000 disaccharide units in proteoglycans.
 Oligosaccharides
Help define protein structure:
Attached at sequences that form surface loops or turns,
and tend to project away form the protein surface due to
their hydrophilic nature.
Conformationally mobile, can occupy
time-averaged volumes of considerable
size.
Shield protein surface, which may
modify its activity or protect it from
proteolysis.
Allowed conformations of (GlcNac)2(mannose)5-9 attached
to ribonuclease B.
 Oligosaccharides
Mediate recognition events:
All cells are coated with sugars in the form of
glycoconjugates, i.e. glycoproteins and glycolipids, which
form a fuzzy layer up to 1400 Å think is some cells.

Lectins are proteins that bind

carbohydrates, which are ubiquitous
in nature and frequently appear on
the surface of cells. They can
recognize individual
monosaccharides in a particular
linkages to other sugars in an
oligosaccharide.
 Oligosaccharides
Antigentic determinants:
Carbohydrates on cell surfaces are some of the best known
immunochemical markers.

The ABO blood group antigens are oligosaccharide

components of glycoproteins and glycolipids on the surface
of an individual's cells.

Individuals with type A cells have type A antigens and carry

anti-B antibodies in their blood. Consequently, transfusion
of type B blood into a type A individual results in an anti-B
antibody-B antigen reaction, which clumps together the
transfused erythrocytes.