Biochemistry II (BIC201M-MBIA021)

School of Science and Technology

CHAPTER 16

Carbohydrates - Sugars and Polysaccharides

2020
 Overview of carbohydrates
• Abundant molecules on earth.
• Sugar and starch – staple human diet
• Carbohydrate Oxidation- central to energy yielding pathways in
most non-photosynthetic cells

• Insoluble carbohydrate- serve as:

– structural and protective elements in cells of bacteria and
plants

– In connective tissues and cell coats of animals

• Complex carbohydrate- covalently attached to proteins and lipids

– Act as signals that determine intracellular location and
metabolic fates of glycoconjugates (different categories such
as glycoproteins, glycopeptides, peptidoglycans, glycolipids, and
lipopolysaccharides).
 Contents of this chapter
• Introduction to carbohydrates
• Monosaccharides: nomenclature,
stereochemistry, & cyclic forms
• Sugar derivatives
• Glycosidic bonds & disaccharides
• Polysaccharides - amylose, amylopectin &
cellulose
• Glycosaminoglycans & proteoglycans
• Oligosaccharides of glycoproteins &
glycolipids
• Lectins
 Empirical formula/structure of
carbohydrates
• Carbohydrates (also referred to as glycans) have
the basic composition:

• They are polyhydroxy aldehydes or ketones.

Explain these terms and furthermore, use this
formula to develop a suitable structure(s).

• E.g glucose has (CH2O)6 or C6(H2O)6

• Not all carbohydrates accommodate this formula
as some have nitrogen, phosphorus and sulphur
 Major classes of carbohydrates
• Monosaccharides - simple sugars, with multiple
hydroxyl groups.

– Based on the number of carbons (e.g., 3, 4, 5, or 6) a

monosaccharide is a triose, tetrose, pentose, or hexose,
etc.
– n is 3 or greater (n is usually 5 or 6 but can be up to 9).

• Disaccharides - two monosaccharides covalently linked

• Oligosaccharides - a few monosaccharides covalently

linked.

• Polysaccharides - polymers consisting of chains of

monosaccharide or disaccharide
 Monosaccharide
• Can be single polyhydroxy aldehyde
(aldose) or single polyhydroxy ketone
(ketose)

• Simplest monosaccharide's contain 3-C

atoms and are called trioses,
• E.g Glyceraldehyde is aldotriose and
dihydroxyacetone (ketotriose)

• Most abundant monosaccharide in nature

is D-glucose.
).

Basic features of monosaccharides

• The basic feature that makes an aldose different from a
ketose is the position of the carbonyl group of the
monosaccharide.
• As seen below, an aldose has the carbonyl group at
Carbon #1 (affording an aldehyde) while a ketose has the
carbonyl group at Carbon #2 (affording a ketone).
 Monosaccharide
• Aldoses (e.g., glucose) have an aldehyde at one
end.
• Ketoses (e.g., fructose) have a keto group,
usually at C #2.
Aldehyde and ketone
 Nomenclature for stereoisomers:
• Chiral (assymetric) carbon: carbon atom containing four chemical
group.
• The group can be arranged to form two different isomers that
are mirror images of each other and not superimposable
• D and L designations are based on the configuration about the
single asymmetric carbon in glyceraldehyde.
• The lower representations are:
– Fischer Projections.
– Monosaccharides are stereoisomers.
 Monossacharides have assymetric
centers
• All monosaccharides (except dihydroxyacetone) contain
one or more assymetric (chiral) carbon atoms.

• These molecules are stereoisomers (enantiomers) and

epimers.

– Stereoisomers : same chemical formula but differ in the

position of the hydroxyl group on one or more assymetric
carbons.

– Epimers are stereoisomers that differ in the position of the

hydroxyl group at only one of the assymetric carbons.

– Diastereomers: not superimposable, non-mirror images

stereoisomers. E.g. D-erythrose and D-threose.
 Examples of monosaccharides as mirror images
• These molecules they are in Fisher Projection formulas.
• D and L designations are based on the configuration about the single
asymmetric carbon in glyceraldehyde.
• For sugars with more than one chiral center, the D or L designation
refers to the asymmetric carbon farthest from the aldehyde or
keto group as occurs on glucose.
 Stereoisomers
• Other stereoisomers have unique names, e.g.,
glucose, mannose, galactose, etc. Compare these
sugars in terms of stereoisomeric or epimers.

• The number of stereoisomers is 2 n, where n is the

number of asymmetric centers.
• The six-carbon aldoses have 4 asymmetric centers,
and thus 16 stereoisomers (8 D-sugars and 8 L-
sugars).

• Student self-assessment: (formulate ALL the D-

sugars and L-sugars stereoisomers from 6-C aldoses.
Please make sure you make some time for this work
and notify mu office on this tutorial.
 1:1 ratio of hemiacetal and hemiketal
• An aldehyde can react with an alcohol to form a
hemiacetal.
• Similarly a ketone can react with an alcohol to form a
hemiketal.
• Student self assessment: What would happen if
alcohol reacts more in one of these reactions?
 Monosaccharide occur in cyclic forms
(Ring structures)
• Exists in solution as ring structures in which:
– Carbonyl group (Aldehyde or ketone) react
with hydroxyl group to form 5 or 6 numbered
ring.
– The Oxygen on the –OH form part of the
ring.
– The carbonyl group which now contains –OH
become anomeric carbon atom.
– A –OH group on the anomeric carbon drawn
down below the ring in the α-position, drawn
up the ring is β-position.
 Cyclic structures
• Pentoses and hexoses can cyclize, as the aldehyde or keto group
reacts with a hydroxyl on one of the distal carbons.
• E.g., glucose forms an intra-molecular hemiacetal by reaction of the
aldehyde on C1 with the hydroxyl on C5, forming a six-member
pyranose ring, named after the compound pyran.
• The representations of the cyclic sugars at right are called
Haworth projections.
• Principle of Monossacharides cyclic
Structure: For a D-sugar, any group written to the
Right of a carbon in Fisher projection has a
Downward direction in Harworth Projection.
 Fructose can form either:
• A 6-member pyranose ring, by reaction of the
C2 keto group with the hydroxyl on C6
• A 5-member furanose ring, by reaction of the
C2 keto group with the hydroxyl on C5.
 Cyclic Structures and Anomeric Forms
Conversion of projections
In the Haworth Stucture: Fischer Structure
•
1. Carbon-#1 is the hemiacetal • . Carbon-1 “*” is the
carbon (with α ), in the Haworth
structure anomeric carbon in
• 2. All of the atoms on the right Harworth
are pointed down in the Haworth
structure. • 2. The anomeric carbon is
• 3. All of the atoms on the left derived from the C=O in
are pointed up in the Haworth the Fischer projection.
structure.
• 4. The CH2OH (the carbon-#6 in • 3. Notice there are no
D-glucose) is pointed up in the carbonyls in the Haworth
Haworth structure
• 5. The OH attached to carbon- projection.
#5 (box around it) becomes • 4. The carbonyl has
part of the ring.
• 6. The linear Fischer projection become the hemiacetal
becomes a cyclic hemiacetal in group.
the Haworth structure.
 CONVERTING FISCHER PROJECTIONS OF
“D” MONOSACCHARIDES INTO HAWORTH
STRUCTURES
Fisher projection

O O O
H H H
CH2OH
H OH H OH H OH H OH H

HO H HO H rotate HO H rotate O
C4-C5 HO
H OH H OH H OH 90o clockwise
clockwise H OH H OH H
H OH H OH HOCH2 H
CH2OH CH2OH OH
D-glucose D-glucose D-glucose

CH2OH CH2OH

H O H H OH CH2OH
H H H OH H
H
OH H OH H O
OH HO
HO OH
O H OH H OH H
H OH H OH
alpha-D-glucose
Haworth structure
Cyclic Structures and Anomeric Forms
Conversion of projections
 Cyclization of glucose
•produces a new asymmetric center at C1,
with the two stereoisomers called anomers,
a & b.
 Chair conformation
• Because of the tetrahedral nature of carbon bonds, the cyclic form
of pyranose sugars actually assume a "chair" or "boat"
configuration, depending on the sugar
• The representation at right reflects the chair configuration of the
glucopyranose ring more accurately than the Haworth projection.
 Monosaccharaides are reducing agents
oxidation-reduction in sugars
• Oxidation of sugars play a key role in Biochemistry.
• Sugars can be oxidized by ferric and Cu ions.
• Carbonyl carbon is oxidized to carboxylic acid.
• Glucose and other sugars have a capacity to reduce the
agent, and are called Reducing sugars.
• use Fehling and Tollens reagents to test the presence of
reducing sugar in the blood.
• It is also possible to estimate the concentration of that
sugar.
Reducing sugars
 Derivatives of Monosaccharides
• A variety of chemical and enzymatic reactions produce
derivatives of the simple sugars. These modifications produce a
diverse array of saccharide derivatives. Some of the most
common derivations are discussed here.
• Sugar alcohol - lacks an aldehyde or ketone. An example is
ribitol.
 Derivatives of Monosaccharides
Sugar acid - the aldehyde at C1, or the hydroxyl on the
terminal carbon, is oxidized to a carboxylic acid. Examples are
gluconic acid and glucuronic acid.

Sugar Acids
• Sugars with free anomeric carbon atoms are reasonably
good reducing agents and will reduce hydrogen peroxide,
ferricyanide , certain metals (Cu2+ and Ag+), and other
oxidizing agents. Such reactions convert the sugar to a
sugar acid. For example, addition of alkaline CuSO4 (called
Fehling’s solution) to an aldose sugar produces a red
cuprous oxide (Cu2O) precipitate
 Derivatives of Monosaccharides
Amino sugar - an amino group substitutes for one of the
hydroxyls. An example is glucosamine. The amino group may be
acetylated. At right, the acetic acid moiety is shown in red.

Amino sugars, including D-glucosamine and D-galactosamine ,

contain an amino group (instead of a hydroxyl group) at the C-
2 position. They are found in many oligo- and polysaccharides,
including chitin, a polysaccharide in the exoskeletons of
crustaceans and insects.
 Muramic acid and neuraminic acid
• Are components of the polysaccharides of cell membranes of higher organisms and
also bacterial cell walls, are glucosamines linked to three-carbon acids at the C-1 or
C-3 positions. In muramic acid (thus named as an amine isolated from bacterial cell
wall polysaccharides.
• Murus is Latin for “wall”), the hydroxyl group of a lactic acid moiety makes an ether
linkage to the C-3 of glucosamine .
• Neuraminic acid (an amine isolated from neural tissue) forms a C-C bond between
the C-1 of N- acetylmannosamine and the C-3 of pyruvic acid.
• The N-acetyl and N- glycolyl derivatives of neuraminic acid are collectively known
as sialic acids and are distributed widely in bacteria and animal systems.
 Derivatives of Monosaccharides
• Acetals , Ketals , and Glycosides
• Hemiacetals and hemiketals can react with alcohols in the presence of acid to
form acetals and ketals, as shown. This reaction is another example of a
dehydration synthesis and is similar in this respect to the reactions undergone
by amino acids to form peptides and nucleotides to form nucleic acids.

• The pyranose and furanose forms of monosaccharides react with alcohols in this
way to form glycosides with retention of the a- or b-configuration at the C-1
carbon. The new bond between the anomeric carbon atom and the oxygen atom
of the alcohol is called a glycosidic bond. Glycosides are named according to the
parent monosaccharide. For example, methyl-ß-D- glucoside can be considered a
derivative of ß-D-glucose.

R-OH + HO-R' --> R-O-R' + H2O

 Some important oligosaccharides
• Oligomers occurs as disaccharides? Why?
• Occurs by linking two monosaccharide
together.
• Three of these examples are dissaccharides
such maltose, sucrose and lactose.
• These molecules are joined together by the
Glycosidic bonding.
• These sugars have no free anomeric carbon,
because of the glycosidic bonding.
• As in proteins and nucleic acids, each
individual unit in an oligosaccharide is
termed a residue.
 Maltose
• Maltose, a cleavage product of starch (e.g.,
amylose, see below), is a disaccharide with an
α(1>4) glycosidic linkage between the C1
hydroxyl of one glucose and the C4 hydroxyl of
a second glucose. Maltose is the a anomer,
because the O at C1 points down from the ring.
• Yeasts hydrolyze starch (barley malt) by
specific enzyme to maltose and then to glucose
which is fermented in the brewing beer.
 Properties of Maltose
• Maltose, isomaltose , and cellobiose are all homodisaccharides
because they each contain only one kind of monosaccharide,
namely, glucose.

• Maltose is produced from starch (a polymer of a-D-glucose

produced by plants) by the action of amylase enzymes.

• It is a component of malt, a substance obtained by allowing grain

(particularly barley) to soften in water and germinate.

• The enzyme diastase, produced during the germination process,

catalyzes the hydrolysis of starch to maltose.

• Maltose is used in beverages (malted milk, for example), and

because it is fermented readily by yeast, it is important in the
brewing of beer.

• In both maltose and cellobiose , the glucose units are 1>4 linked,
meaning that the C-1 of one glucose is linked by a glycosidic bond
to the C-4 oxygen of the other glucose.
 Dissaccharides

The structures of several important disaccharides. Note that the notation -

HOH means that the configuration can be either a or b. If the -OH group is
above the ring, the configuration is termed β. The configuration is a if the -
OH group is below the ring as shown. Also note that sucrose has no free
anomeric carbon atoms.
 Cellobiose
• Cellobiose, a product of cellulose breakdown, is the
otherwise equivalent b anomer. The configuration at
the anomeric C1 is β (O points up from the ring). The
β (1>4) glycosidic linkage is represented as a "zig-
zag" line, but one glucose residue is actually flipped
over relative to the other. (See Chime view of
cellulose below.)
 Other disaccharides include
• Sucrose, common table sugar, has a glycosidic bond linking the
anomeric hydroxyls of glucose and fructose.

• Because the configuration at the anomeric carbon of glucose is α (O

points down from the ring), the linkage is designated α(1>2).

• The full name is α-D-glucopyranosyl-(1>2) β -D- fructopyranose.

• When animal consume sucrose, it is hydrolysed to glucose and
fructose for energy.

• is a disaccharide of almost universal appeal and tolerance. Produced

by many higher plants
• Sucrose is also easily hydrolyzed by dilute acid, apparently because
the fructose in sucrose is in the relatively unstable furanose form.

• Although sucrose and maltose are important to the human diet, they
are not taken up directly in the body.
• In a manner similar to lactose, they are first hydrolyzed by sucrase
and maltase, respectively, in the human intestine.
 Homodissaccharides and
heterodissacharides
• Maltose, isomaltose , and cellobiose are
all homodisaccharides

– because they each contain only one kind of

monosaccharide, namely, glucose 1 of the
beta form galactose and C-4 of glucose
 Lactose
• Lactose, milk sugar, is composed of glucose and
galactose with β(1>4) linkage from the anomeric
hydroxyl of galactose. Its full name is β -D-
galactopyranosyl-(1>4)-α-D-glucopyranose..
• The glycosidic bond is β(1>4), between the anomeric
carbon C-
 Structure and functions of polysaccharides
• polymers consisting of chains of monosaccharide or
disaccharide units.

• Maltose, isomaltose , and cellobiose are all

homodisaccharides because they each contain only one
kind of monosaccharide, namely, glucose.

• By far the majority of carbohydrate material in

nature occurs in the form of polysaccharides.

• By our definition, polysaccharides include not only

those substances composed only of glycosidically
linked sugar residues
– but also molecules that contain polymeric saccharide
structures linked via covalent bonds to amino acids,
peptides, proteins, lipids, and other structures.
 Polysaccharides
• Polysaccharides, also called glycans, consist of
monosaccharides and their derivatives.

• If a polysaccharide contains only one kind of monosaccharide

molecule, it is a homopolysaccharide, or homoglycan;
– whereas those containing more than one kind of
monosaccharide are heteropolysaccharides.

– The most common constituent of polysaccharides is D-

glucose, but D-fructose, D-galactose, L-galactose, D-
mannose, L-arabinose, and D-xylose are also common.

– Common monosaccharide derivatives in polysaccharides

include the amino sugars (D-glucosamine and D-
galactosamine ), their derivatives (N-acetylneuraminic acid
and N-acetylmuramic acid), and simple sugar acids
(glucuronic and iduronic acids).
 Polysaccharides`1`
• Homopolysaccharides are often named for
the sugar unit they contain, so that glucose
homopolysaccharides are called glucans,
while mannose homopolysaccharides are
mannans.

• Other homopolysaccharide names are just as

obvious: galacturonans, arabinans, and so on.
• Homopolysaccharides of uniform linkage type
are often named by including notation to
denote ring size and linkage type. Thus,
cellulose is alpha (1> 4)-beta-D-glucopyranan.
 Polysaccharides
• Polysaccharides differ not only in the nature of
their component monosaccharides but also in the
length of their chains and in the amount of chain
branching that occurs.

• Although a given sugar residue has only one

anomeric carbon and thus can form only one
glycosidic linkage with hydroxyl groups on other
molecules, each sugar residue carries several
hydroxyls, one or more of which may be an
acceptor of glycosyl substituents.

• This ability to form branched structures

distinguishes polysaccharides from proteins and
nucleic acids, which occur only as linear polymers.
 Storage polysaccharides
• Storage polysaccharides are an important
carbohydrate form in plants and animals.

• It seems likely that organisms store

carbohydrates in the form of polysaccharides
rather than as monosaccharides to lower the
osmotic pressure of the sugar reserves.

• Because osmotic pressures depend only on

numbers of molecules, the osmotic pressure is
greatly reduced by formation of a few
polysaccharide molecules out of thousands (or
even millions) of monosaccharide units.
 Storage polysaccharides
• Plants store glucose as amylose or amylopectin, glucose polymers
collectively called starch. Glucose storage in polymeric form
minimizes osmotic effects.

• Starch, exists in two forms: a-amylose and amylopectin

• Most forms of starch in nature are 10 to 30% a-amylose and 70 to

90% amylopectin. Typical cornstarch produced in the United States
is about 25% a-amylose and 75% amylopectin.

• α-Amylose is composed of linear chains of D-glucose in α(1 > 4)

linkages.
-The chains are of varying length, having mo- lecular weights
from several thousand to half a million. As can be seen from
the structure, the chain has a reducing end and a nonreducing
end.
 Storage polysaccarides
• In animals, digestion and use of plant starches begins in the mouth
with salivary α -amylase (α(1>4)-glucan 4-glucanohydrolase), the
major enzyme secreted by the salivary glands.

• Although the capability of making and secreting salivary a-

amylases is widespread in the animal world, some animals (such as
cats, dogs, birds, and horses) do not secrete them.

• Salivary a-amylase is an endoamylase that splits α(1>4) glycosidic

linkages only within the chain. Raw starch is not very susceptible to
salivary endoamylase . However, when suspensions of starch
granules are heated, the granules swell, taking up water and
causing the polymers to become more accessible to enzymes.

• Thus, cooked starch is more digestible. In the stomach, salivary a-

amylase is inactivated by the lower pH, but pancreatic secretions
also contain a-amylase.
 Storage polysaccarides
• . β-Amylase, an enzyme absent in animals
but prevalent in plants and microorganisms,

– cleaves disaccharide (maltose) units from the

termini of starch chains and is an exoamylase.

– neither a-amylase nor b-amylase, however, can

cleave the α(1>6) branch points of amylopectin ,
and once again, α (1>6)-glucosidase is required to
cleave at the branch points and allow complete
hydrolysis of starch amylopectin.
 Form of starch: Amylose
• Plants store glucose as amylose or amylopectin,
glucose polymers collectively called starch. Glucose
storage in polymeric form minimizes osmotic effects.

• Amylose is a glucose polymer with α(1>4) glycosidic

linkages, as represented. The end of the
polysaccharide with an anomeric carbon (C1) that is
not involved in a glycosidic bond is called the reducing
end.
 Amylopectin
• Amylopectin is a glucose polymer with mainly α
(1>4) linkages, but it also has branches formed
by α (1>6) linkages. The branches are generally
longer. The branches produce a compact
structure, and provide multiple chain ends at
which enzymatic cleavage of the polymer can
occur.
 Forms of starch

Amylose and amylopectin are the two forms of starch. Note that the linear
linkages are α(1 >4), but the branches in amylopectin are α(1 >6). Branches in
polysaccharides can involve any of the hydroxyl groups on the
monosaccharide components. Amylopectin is a highly branched structure,
with branches occurring every 12 to 30 residues.
 Glycogen
• The major form of storage polysaccharide in animals is glycogen similar
to amylopectin.

• Glycogen is found mainly in the liver (where it may amount to as much as

10% of liver mass) and skeletal muscle (where it accounts for 1 to 2% of
muscle mass).

• Liver glycogen consists of granules containing highly branched

molecules, with α(1>6) branches occurring every 8 to 12 glucose units.

• Like amylopectin, glycogen yields a red-violet color with iodine.

• Glycogen can be hydrolyzed by both α- and β -amylases, yielding glucose
and maltose, respectively, as products and can also be hydrolyzed by
glycogen phosphorylase, an enzyme present in liver and muscle tissue,
to release glucose-L-phosphate.

• The highly branched structure permits rapid release of glucose from

glycogen stores, e.g., in muscle cells during exercise. The ability to
rapidly mobilize glucose is more essential to animals than to plants.
 Starch phosphorylase reaction
• The starch phosphorylase reaction cleaves glucose residues
from amylose, producing a-D-glucose-L-phosphate
• Glucose-L-phosphate units are thus delivered to the plant cell,
suitable for further processing in glycolytic pathways
 Structural Polysaccharides
cellulose
• The structural polysaccharides have properties that are
dramatically different from those of the storage polysaccharides,
even though the compositions of these two classes are similar.
• The structural polysaccharide cellulose is the most abundant natural
polymer found in the world.
• Found in the cell walls of nearly all plants, cellulose is one of the
principal components providing physical structure and strength.
• The wood and bark of trees are insoluble, highly organized
structures formed from cellulose and also from lignin.
• consists of long linear chains of glucose, with β(1>4) linkages. Every
other glucose in cellulose is flipped over, due to the β-linkages
 Cellulose
• Cellulose is extremely resistant to hydrolysis, whether by acid or by the
digestive tract amylases described earlier. As a result, most animals (including
humans) cannot digest cellulose to any significant degree.

• Ruminant animals, such as cattle, deer, giraffes, and camels, are an exception
because bacteria that live in the rumen secrete the enzyme cellulase, a β-
glucosidase effective in the hydrolysis of cellulose.
•
• The resulting glucose is then metabolized in a fermentation process to the
benefit of the host animal.
• Termites and shipworms ( Teredo navalis ) similarly digest cellulose because
their digestive tracts also contain bacteria that secrete cellulase.
•
Chitin
A polysaccharide that is similar to cellulose, both in its biological function and its
primary, secondary, and tertiary structure, is chitin.

• Chitin is present in the cell walls of fungi and is the fundamental material in the
exoskeletons of crustaceans, insects, and spiders. The structure of chitin, an
extended ribbon, is identical to cellulose, except that the OOH group on each C-2 is
replaced by -NHCOCH3, so that the repeating units are N-acetyl-D-glucosamines in
β(1>4) linkage.

• Chitin is the earth’s second most abundant carbohydrate polymer (after cellulose),
and its ready availability and abundance offer opportunities for industrial and
commercial applications.

• Chitin-based coatings can extend the shelf life of fruits, and a chitin derivative
that binds to iron atoms in meat has been found to slow the reactions that cause
rancidity and flavor loss.

• Without such a coating, the iron in meats activates oxygen from the air, forming
reactive free radicals that attack and oxidize polyunsaturated lipids, causing most
of the flavor loss associated with rancidity.
• Chitin-based coatings coordinate the iron atoms, preventing their interaction with
oxygen.
 Agarose
• An important polysaccharide mixture
isolated from marine red algae
(Rhodophyceae) is agar, which consists of
two components, agarose and
agaropectin.
• Agarose is a chain of alternating D-
galactose and 3,6-anhydro-L-galactose,
with side chains of 6-methyl-D-galactose.
• Agaropectin is similar, but contains in
addition sulfate ester side chains and D-
glucuronic acid.
• The three-dimensional structure of
agarose is a double helix with a threefold
screw axis
 Polysaccharides playing a role in extracellular matrix
• Glycosaminoglycans (mucopolysaccharides) are linear polymers of
repeating disaccharide. The constituent monosaccharides tend to be
modified, with acidic groups, amino groups, sulfated hydroxyl and amino
groups, etc. Glycosaminoglycans tend to be negatively charged, because
of the prevalence of acidic groups.

• Hyaluronate (hyaluronan) is a glycosaminoglycan with a repeating

disaccharide consisting of two glucose derivatives, glucuronate (glucuronic
acid) and N-acetylglucosamine. The glycosidic linkages are β (1>3) and β
(1>4).
 Dextran
• Another important family of storage
polysaccharides are the dextrans , which are
α(1>6)-linked polysaccharides of D-glucose with
branched chains found in yeast and bacteria
• Dextran is a branched polymer of D-glucose
units. The main chain linkage is α (1>6), but 1>2,
1>3, or 1>4 branches can occur.
 Sephadex
• Sephadex gels are formed from dextran chains cross-
linked with epichlorohydrin. The degree of cross-linking
determines the chromatographic properties of Sephadex
gels. Sephacryl gels are formed by cross-linking of
dextran polymers with N,N9-methylene bisacrylamide.

• These preparations (known by various trade names such as

Sephadex and Bio-gel) are extremely hydrophilic and swell
to form highly hydrated gels in water.
• Depending on the degree of cross-linking and the size of
the gel particle, these materials form gels containing from
50 to 98% water. Dextran can also be cross-linked with
other agents, forming gels with slightly different
properties.
Sephadex
•
glycosaminoglycans
A class of polysaccharides known as glycosaminoglycans is involved in a
variety of extracellular (and sometimes intracellular) functions.
Glycosaminoglycans consist of linear chains of repeating disaccharides in
which one of the monosaccharide units is an amino sugar and one (or
both) of the monosaccharide units contains at least one negatively
charged sulfate or carboxylate group.
 Proteoglycans: Glycosaminoglycans
• Heparin, with the highest net negative
charge of the disaccharides shown, is a
natural anticoagulant substance.

• It binds strongly to antithrombin III (a

protein involved in terminating the
clotting process) and inhibits blood
clotting.
 Heparan
• Heparan sulfate is initially synthesized on a membrane-
embedded core protein as a polymer of alternating
glucuronate and N-acetylglucosamine residues.

• Later, in segments of the polymer, glucuronate residues

may be converted to the sulfated sugar iduronic acid, while
N-acetylglucosamine residues may be deacetylated and/or
sulfated.

• Heparin, a soluble glycosaminoglycan found in granules of

mast cells, has a structure similar to that of heparan
sulfates, but is relatively highly sulfated.

– When released into the blood, it inhibits clot formation by

interacting with the protein antithrombin. Heparin has an
extended helical conformation. Charge repulsion by the many
negatively charged groups may contribute to this
conformation.
 Heparan
• Some cell surface heparan sulfate glycosaminoglycans
remain covalently linked to core proteins associated with
the plasma membrane.
• The core protein of a syndecan heparan sulfate
proteoglycan includes a single transmembrane a-helix,
as in the simplified diagram at right.
• The core protein of a glypican heparan sulfate
proteoglycan is attached to the outer surface of the
plasma membrane via covalent linkage to a modified
phosphatidylinositol lipid
 Other Glycosaminoglycans
• Hyaluronate molecules may consist of as many as
25,000 disaccharide units, with molecular
weights of up to 107. Hyaluronates are important
components of the vitreous humor in the eye and
of synovial fluid, the lubricant fluid of joints in
the body.

• The chondroitins and keratan sulfate are found

in tendons, cartilage, and other connective tissue,
whereas dermatan sulfate, as its name implies, is
a component of the extracellular matrix of skin.

• Glycosaminoglycans are fundamental constituents

of proteoglycans (discussed later).
Proteins involved in signaling & adhesion at the cell surface recognize
& bind heparan sulfate chains.
E.g., binding of some growth factors (small proteins) to cell surface
receptors is enhanced by their binding also to heparan sulfates.
Regulated cell surface Sulf enzymes may remove sulfate groups at
particular locations on heparan sulfate chains to alter affinity
for signal
proteins, e.g., iduronate-2-sulfate N-sulfo-glucosamine-6-sulfate
growth factors. H CH2OSO3

H O H O H
COO H
OH H O OH H
H O

H OSO3 H NHSO3
heparin or heparan sulfate - examples of residues
• Glycosamiminoglycans
 Oligosaccharides of glycoproteins and glycolipids
• Oligosaccharides that are covalently attached to proteins
or to membrane lipids may be linear or branched chains.
They often include modified sugars, e.g.,
acetylglucosamine, etc.

• Most important one are involved in immune response.

• O-linked oligosaccharide chains of glycoproteins vary in
complexity. They link to a protein via a glycosidic bond
between a sugar residue and a serine or threonine
hydroxyl. O-linked oligosaccharides have roles in
recognition, interaction.
 Glycoproteins
• N-acetylglucosamine (abbreviated GlcNAc) is a common O-linked
glycosylation of protein serine or threonine residues. Many cellular
proteins, including enzymes and transcription factors, are
regulated by reversible attachment of GlcNAc.

• Often attachment of GlcNAc to a protein hydroxyl group

alternates with phosphorylation, with these two modifications
having opposite regulatory effects (stimulation or inhibition).
 Glycoproteins
• N-linked oligosaccharides of glycoproteins tend to be complex
and branched.
• Initally N-acetylglucosamine is linked to a protein via the side-
chain N of an asparagine residue in a particular 3-amino acid
sequence.
• Additional monosaccharides are added, and the N-linked
oligosaccharide chain is modified by removal and addition of
residues, to yield a characteristic branched structure, as at
right.
 Glycoproteins
• Many proteins secreted by cells have attached N-linked
oligosaccharide chains.
• Genetic diseases have been attributed to deficiency of
particular enzymes involved in synthesizing or modifying
oligosaccharide chains of these glycoproteins.
• Such diseases, and gene knockout studies in mice, have been
used to define pathways of modification of oligosaccharide
chains of glycoproteins and glycolipids.
 Glycoproteins
Lectins

• Lectins are glycoproteins that recognize and bind to specific

oligosaccharides. Concanavalin A and wheat germ agglutinin are
plant lectins that have been useful research tools.

• The C-type lectin-like domain is a Ca++-binding carbohydrate

recognition domain present in many animal lectins.

• Recognition and binding of carbohydrate moieties of

glycoproteins, glycolipids, and

• proteoglycans by animal lectins is a factor in cell-cell recognition,

adhesion of cells to the extracellular matrix, interaction of cells
with chemokines and growth factors, recognition of disease-
causing microorganisms, and initiation and control of inflammation.
 Types of Lectins
• Mannan-binding lectin (MBL) is a glycoprotein found in blood plasma. It binds cell
surface carbohydrates of disease-causing microorganisms and promotes
phagocytosis of these organisms as part of the immune response.

• Selectins are integral proteins of mammalian cell plasma membranes with roles in
cell-cell recognition and binding. The C-type lectin-like domain is at the end of a
multi-domain extracellular segment extending outward from the cell surface.

• A cleavage site just outside the transmembrane a-helix provides a mechanism for
regulated release of some lectins from the cell surface. A cytosolic domain
participates in regulated interaction with the actin cytoskeleton.