Chapter 11

Sugars and Polysaccharides

Instructor: Rashid Syed

Textbook: Biochemistry (4th Edition ) by Donald Voet Judith G. Voet

Carbohydrates
General formula (CH2O)n or Cn(H2O)n (carbon-hydrates)
Also known as saccharides or sugars
They serve as energy stores or fuel
They are components of DNA and RNA
They are the primary component of cell walls of bacteria
and plants
Glycoconjugates are carbohydrates linked to proteins and
lipids to form key intermediates and regulators of
physiological processes
Glycobiology is the study of carbohydrate-containing
biomolecules

Monosaccharides
They are polyhydroxy aldehydes (aldose) or ketones
(ketose).
Carbon chain from 3 to 9 with general name of triose,
hexose etc or aldohexose, ketohexose etc.
Fischer projection formulas are written as linear C chains
with the aldehyde numbered as C1 in aldoses and ketone as
C2 in ketoses.
Each monosaccharide (except dihydroxyacetone) has at
least one chiral carbon. The highest numbered C is
generally achiral
The orientation of the OH around the chiral carbons
determines the identity of the sugar.

Stereoisomers

D-Glyceraldehyde

L-Glyceraldehyde

Aldoses and Ketoses

Stereoisomers
The (n-1) C determines the enantiomeric form of the sugar.
If the hydroxyl on Cn-1 is to the left, it is the L-isoform; if
the n-1 hydroxyl is to the right, it is the D isoform.
Enantiomers are mirror-images of each other. Most sugars
in biomolecules exist in the D-form
All the aldose and ketose stereoisomers with the same
number of C atoms but not mirror images of each other are
called diastereomers.
Usually there are n-2 chiral carbons in aldoses (n-3 in
ketoses). There are 2(n-2) possible aldose stereoisomers
(enantiomers + diastereoisomers)
Two sugars that differ in the orientation of only one
hydroxyl are called as epimers of each other. Eg: glucose,
mannose and galactose

D-Aldoses

D-Ketoses

Epimers

Formation of Hemiacetals and Hemiketals

Cyclization of Glucose

Mutarotation: interconversion of and anomers:

Haworth Projections
Alcohols react with aldehydes to form hemiacetals and with
ketones to form hemiketals
Most long-chain aldoses and ketoses form intramolecular
hemiacetals / hemiketals to form 5-(furanose) or 6- (pyranose)
membered ring structures.
The ring-form depictions of monosaccharide structures are
called Haworth projections. When converting Fischer to
Haworth formulas follow the rule: right down (except for C5)
Ring formation results in C1 becoming a chiral carbon. The
-anomer is when OH is below and -anomer is when OH
is above the plane of the ring
Complete name of sugar includes: anomer, enantiomer, sugar
identity and ring type. Eg: -D-Glucopyranose

Pyranose and Furanose

Chair Conformations

-D-Glucopyranose
puts all the hydroxyls
equatorial
nice and stable!

Important Modified Monosaccharides

Glucosamine/Galactosamine: -OH on C2 is replaced by NH2
The amines are usually esterified with acetic acid to form Nacetylglucosamine and N-acetylgalactosamine
Glucuronic / galactouronic acid: C6 is oxidized to COOH.
These modified monosaccharides are abundantly found in
mucopolysaccharides and glycosaminoglycans
Neuraminose is a 9 C ketose. In sialic acid (Nacetylneuraminic acid) C1 is oxidized to COOH and C5 has a
N-acetyl group. Sialic acid is the terminal sugar of
oligosaccharides found on glycoproteins
Sulfated polysaccharides: The OH on C4 or C6 may be
sulfated (-OH to -OSO3-) on several glycosaminoglycans. The
degree of sulfation is variable

Reactions of monosaccharides
Monosaccharides have a free carbonyl group which is prone to
oxidation. Thus, monosaccharides reduce other compounds.
Any sugar with a free carbonyl C is called a reducing sugar
A hemiacetal can react with an alcohol or an amine to form an
adduct with the removal of H2O. The resulting bond with an
alcohol results in an O-glycosidic linkage. Reaction with an
amine results in a N-glycosidic bond
O-glycosidic linkages can join one monosaccharide to another
to form polymers. These are called as disaccharides,
oligosaccharides or polysaccharides.
Polysaccharides may be linear or branched. The repeating
unit may be a monosaccharide or a disaccharide.

Sugars are reducing

agents

O-Glycosidic Linkages
Two monosaccharides are linked covalently by a
O-glycosidic linkage
Formed when OH of one sugar reacts with the
anomeric carbon of a second sugar to form an
acetal
The acetal C is no longer a reducing sugar.
A polysaccharide has reducing and non-reducing
ends
O-glycosidic linkages are hydrolyzed by acid but
resistant to base.

Formation of Maltose

Rules for naming oligosaccharides

Oligosaccharide names are written in the following
sequence:
Anomeric configuration of sugar 1
Non-reducing sugar (sugar 1) including it ring
conformation derivatized to end in -yl
In parentheses carbon atoms linked by bond are
identified with an arrow going from carbon of first to
second sugar
Second sugar is named. Eg. Maltose is:
-D-glucopyranosyl (14) D-glucopyranose
Names can be abbreviated: 3-letter code for sugar,
anomeric orientation included in parentheses with
linkage. Eg: Maltose: Glc(14)Glc

Complex Carbohydrates
Disaccharides and polysaccharides formed by O-glycosidic
linkages between monosaccharides are called complex
carbohydrates
In sucrose, the carbonyl carbons of both glucose and
fructose participate in the O-glycosidic linkage, so it is a
non-reducing sugar.
Lactose formed from glucose and galactose is the
disaccharide of milk.
Polysaccharides contain more than 2 monomeric sugars
Homopolysaccharides are repeats of the same monomer,
heteropolysaccharides contain a disaccharide repeating unit

Carbohydrate Nomenclature

A useful website if you need a detailed explanation or

clarification for naming any carbohydrate molecule.

http://www.chem.qmul.ac.uk/iupac/2carb/

Common Disaccharides:

Sucrose is the most chemically stable of the four:

the only one without a hemiacetal.

Polysacchardies

Polysaccharides
Storage polysaccharides: Starch and glycogen are polymers
of glucose in (14) linkages with (16) branches. Starch
is a mixture of amylose (linear) and amylopectin (branched).
Glycogen is highly branched (every 8-12 units)
Structural polysaccharides: Cellulose makes up the cell wall
of plant cells. It is a polymer of glucose in (14) linkages.
Other eg: chitin, pectin.
Mucopolysaccharides/glycosaminoglycans: Very viscous
heteropolysaccharides found in extracellular cavities and
connective tissue. Hyaluronic acid and chondroitin sulfate
serve as lubricants for joints. Heparin is an anticoagulant.
Glycosaminoglycans attach to proteins to form proteoglycans.
Carbohydrates, rather than protein are the main component

Starch and Glycogen

Plants store glucose as starch, animals as glycogen
Both polymers are greatly hydrated; total mol. wt. up to
1 million. 3-D structure is coiled-helical.
Glycogen is highly branched; each molecule has one
reducing end and multiple non-reducing ends.
Enzymatic hydrolysis proceeds from non-reducing ends.
Glycogen is abundant in the liver and exists in dense
granules also containing enzymes for glycogen
metabolism
Storage of glucose as glycogen prevents increase in
osmolarity.

Starch: Amylose (linear) and Amylopectin (branched)

3-D structure of amylose

Cellulose and Chitin

These are structural polysaccharides
Cellulose is glc (14). It forms the cell wall of plant cells
(cotton, wood, dietary fiber from veg.)
Chitin is glcNac (14). It is the component of the hard
exoskeleton of insects.
Linear, fibrous and water-insoluble; straight extended
geometry stabilized by inter-chain and intra-chain H-bonds.
Most animals lack the enzyme cellulase that hydrolyzes glc
(14) linkages. Bacteria present in rumen of cattle
secrete cellulase.

Cellulose
and Chitin

Glycosaminoglycans
Heteropolysaccharides found in extracellular matrix
along with fibrous proteins. They facilitate cell-cell
adhesion. Found as lubricant in joints.
Linear, disaccharide is repeating unit. One of the
repeating dimer is glcNac or galNac; it may be sulfated at
C-4 or C-6. in the other sugar, C-6 is COOH.
High charge on molecule. Assumes extended geometry
to avoid repulsion. Binds to basic proteins.
Eg: Hyaluronic acid: found in vitrous humor of eye.
Being developed as a pharmaceutical agent to facilitate
wound-healing. Chondroitin sulfate: used to alleviate
joint aches. Heparin: anti-coagulant.

Glycosamin
o-glycans

Structures to Memorize
*Glyceraldehyde
*Galactose

*Ribose
*mannose
*Dihydroxyacetone

*Glucose
*Fructose

*Lactose: galactose (14)glucose

*Sucrose: glucose ,(12)fructose (non-reducing sugar)
*Starch (Amylose): glucose (14) glucose
*Starch (Amylopectin) / Glycogen: glucose (14) glucose;
branches by (16) linkages
*Cellulose: glucose (1 4) glucose
*Chitin: (1 4) N-acetylglucosamine
*Hyaluronate:
{Glucuronic acid (13) N-acetylglucosamine (14)}n

Proteoglycans
Macromolecules with glycosaminoglycans (GAG) that are
covalently attached to a core protein; GAG mass % greater than
that of protein
Found on outer cell surface (integral protein) or extracellular
matrix & connective tissue (secreted protein)
Functions: cell-cell recognition, adhesion, cell migration,
immune response, wound healing, blood clotting etc.
GAG polymer attaches to ser on sequence S-G-X-G of core
protein through a trisaccharide bridge
Proteoglycan aggregates form when many core proteins associate
with a single molecule of hyaluronic acid. Link proteins at the
junction of HA and core protein stabilize the aggregate.

Proteoglycan
Structure

Proteoglycan Aggregate

Glycoproteins
Glycoproteins are proteins with covalently attached
oligosaccharide groups
Most cell surface proteins as well as secreted proteins are
glycoproteins with the oligosaccharide component essential
for protein activity and function.
Carbohydrates are linked to proteins by O-glycosidic
linkages with ser or thr. They also form N-glycosidic
linkages with Asn. Asn has to be in the seq NXS or NXT.
No specific motif requirement for O-linked Ser / Thr.
All N-linked oligosaccharides have a pentasaccharide core
that grows to various oligosaccharide patterns. Two most
common ones are the high-mannose type and complex type.
The first sugar in O-linked oligosaccharides is usually
galNac.

O-linked glycosylation
Takes place in the Golgi apparatus by the serial
addition of monosaccharide units to a completed
polypeptide chain
End sugar monomer on each branch is sialic acid
Oligosaccharides are synthesized by the action of
enzymes called glycosyl transferases.
Many different glycosyl transferases, each specific for
formation of a specific glycosidic linkages
The monomeric sugar has to be activated in the form
of a sugar nucleotide (UDP- or GDP-sugar) prior to
attachment to the growing oligosaccharide

Importance of Glycosyl transferases in

determining Blood Groups
Specificity of glycosyl transferases is demonstrated by
human ABO blood groups.
The basic O-type oligosaccharide antigen on RBC
membranes is extended with galNac by the action of Nacetylgalactosamine transferease to form A antigen.
In individuals with the B antigen, galactosyl transferase
adds on galactose to the oligosaccharide.
The two enzymes differ by only 4 aa and are absent in Otype individuals due to premature termination of
polypeptide synthesis.

Red Blood Cell

Red Blood Cell

Red Blood Cell

N-linked glycosylation
Starts co-translationally in the ER lumen and
processing continues in the Golgi complex.
A 14-unit oligosaccharide complex is first
assembled on dolichol phosphate, a lipid present
in the ER membrane
The 14-unit oligosaccharide is transferred from
dolichol phosphate to an acceptor Asn on the
nascent protein in the ER
The oligosaccharide is trimmed before the
protein leaves the ER and further modified as it
passes through the Golgi

Glycolipids
Covalent conjugates of lipids and oligosaccharides
Cerebrosides and gangliosides are found in the
brain and nervous tissue
In biomembranes, glycolipids are oriented
asymmetrically with the sugar units always on the
extracellular side of the membrane
Lipopolysaccharides are found on outer membrane
of bacterial cells and are targets of antibodies

Functions of Glycoconjugates
Lectins are proteins that bind oligosaccharides with high
affinity and specificity. Important for cell-cell
recognition and cell adhesion
Removal of sialic acid cap makes glycoprotein a ligand
for galactosyl receptor resulting in its degradation.
Similar mechanism for degradation of RBCs.
P-Selectins on PM of capillary endothelial cells bind to
oligosaccharides on circulating T-lymphocytes and
initiate immune response.
Monocyte adhesion to lectins on endothelial cells of
vasculature initiate the atherosclerotic process.
Viruses and bacteria bind to cell surface glycoproteins
Cholera and pertussis toxins bind to glycolipids.

Oligosaccharide interactions with lectins