6 Carbohydrates

6.
Carbohydrates
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Outline
Introduction
Monosaccharides Glycosides
Nomenclature Oligosaccharides
Aldoses and Ketoses Structure
Enantiomers Distinguishing features of Different
Alternative Designations for Enantiomers: Disaccharides
D-L and R-S
Writing the Structure of Disaccharides
Monosaccharide Enantiomers in Nature
Diastereomers
Stability and formation of glycosidic bond.
Tetrose Diastereomers Polysaccharides
Pentose Diastereomers next lecture
Hexose Diastereomers
Ring Structures
Pentose Rings
Hexose Rings
Sugars with More Than Six Carbons
Derivatives of the Monosaccharides
Phosphate Esters
Acids and Lactones
Alditols
Amino Sugars Prof. G. Gilardi - Biological Chemistry
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Carbohydrates
The term carbo-hydrate derives from the fact that many of them have a formula that
can be simplified to (CH2O)n.
Some of these compounds are chemically modified, however, and do not fit the formula due to
additional amino, sulfate and phosphate groups.
Saccharide is another name for a carbohydrate.

Simple saccharides are the monosaccharides, commonly called sugars.
Glucose is an example of a monosaccharide.
Monosaccharide, oligosaccharide, or polysaccharide refer to compounds composed of a single
sugar, several sugars linked together, or many sugars linked together, respectively.
Saccharides play a variety of roles in living organisms:

Primary energy-generating process in metabolism: rice, wheat, potatoes
Energy storage (monosaccharides and oligosaccharides),
structural roles (polysaccharides): cellulose in plants, cell wall in bacteria, exoskeleton in insects
and arthropods
cell identity (oligosaccharides): cell surface (proteins/lipids), blood type, binding of viruses,
antibodies.
Prof. G. Gilardi - Biological Chemistry
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4
Monosaccharides
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Monosaccharide Nomenclature
Monosaccharides are the simplest sugars, having the formula

(CH2O)n.
The smallest molecules usually considered to be
monosaccharides are those with n = 3: triose
Monosaccharides can be categorized according to their value of

'n,' as shown below:
n Category
3 Triose
4 Tetrose
5 Pentose
6 Hexose
7 Heptose
8 Octose

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(CH2O)3 = TRIOSE:
aldoses and ketoses
There are 2 trioses: D-glyceraldehyde and
dihydroxyacetone
See the formulas:
D- glyceraldehyde is an aldehyde, and therefore
the first member of the class of monosaccharides
called ALDOSES
Dihydroxyacetone is a ketone, and therefore the
first member of the class of monosaccharides
called KETOSES
D-glyceraldehyde is an ALDO-TRIOSE and
dihydroxyacetone is a KETO-TRIOSE

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Tautomers
D- glyceraldehyde and dihydroxyacetone are also TAUTOMERS = structural

isomers with same atomic composition, but different only in the position of the
hydrogens and double bonds.
They can interconvert via an ENEDIOL INTERMEDIATE in dilute alkali or in
catalysed reactions:

8
Enantiomers
Carbons in a monosaccharide are numbered such that the aldehyde group is carbon number one or
the ketone group is carbon number two.
Note that the 2nd C in D-glyceraldehyde is chiral = there are four different groups attached to it
This means that we can draw 2 molecules, D-glyceraldehyde and L-glyceraldehyde that are mirror
images of each other (stereoisomers) and cannot be superimposed on each other = these are
enantiomers
A convenient way to draw enantiomers is the Fisher projection: horizontal bonds are coming towards
you, vertical bonds are receding

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D-L and R-S nomenclatures
D-L nomenclature:
The designation 'D-' or 'L-' is an older nomenclature still used
widely in biochemistry.
It originally described whether the compound rotated a plane of
polarized light to the right (D for dextro) or left (L for left).
This is not absolute because it depends on the reference
compound chosen.
The R-S nomenclature:
It is commonly used by organic chemists
It is an absolute naming scheme (see rules):
Establish the priority of the groups:
OR>OH>NH2>CO2H>CHO>CH2OH>CH3>H
Position the group with lowest priority away from us
Read the sequence; if R rectus or S sinister
BUT it is rarely used by biochemists since it is difficult to apply to
molecules, such as tetroses, pentoses, hexoses, etc., which may
have more than one chiral carbon.
The predominant monosaccharides found in nature have

the 'D' configuration.
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(CH2O)4 = TETROSES:
Diastereoisomers
When we consider sugars with more than 3C, further stereoisomeric forms are possible:
Sugars with more than one asymmetric carbon have many possible 3D configurations.
In general a molecule with m chiral centers will have 2m stereoisomers.
The multiple stereoisomeric forms means that not all stereoisomers will be mirror images of each other.
Stereoisomers that are not mirror images of each other are called diastereomers.
Note: the prefix D- and L- refers to the configuration of the C farthest from the carbonyl group
Stereochemistry of aldo-tetroses: Stereochemistry of keto-tetroses:

2 chiral C (n. 2 and 3) thus 2 diastereoisomeric forms, Only 1 carbon, C3 is chiral, so there
Threose and Erythrose. are only two enantiomers for Erythrulose.
Note the positions of the OH in red.
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(CH2O)5 = PENTOSES
(CH2O)6 = HEXOSES
As we increase the n of carbons, we increase the n of chiral centres
There is no defined nomenclature for the names of the monosaccharides: we
must learn them like we did for the amino acids
Glucose, for example, contains 4 chiral carbons, as the number of possible
stereoisomers is 2m, there are 16 possible stereoisomers. The form most
commonly found in living organisms, D-glucose, has only one mirror image. In
fact, any stereoisomer has only one mirror image. The other 14 stereoisomers
of glucose that are not mirror images of it are diastereomers.
Diastereomers can have very different biological uses. Out of the 8 D-stereoisomers
of D-glucose, galactose and mannose, are commonly found in biological systems,
others, such as D-idose or D-talose, are much rarer.
Some monosaccharides are more used in biochemistry than others:
C3: D-glyceraldehyde, Dihydroxyacetone
C4: D-erythore, D-threose, D-erythrulose
C5: D-ribose, D-arabinose, D-xylose, D-ribulose, S-xylulose
C6: D-glucose, D-mannose, D-galactose, D-fructose

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13
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PENTOSES: Ring structures
When a monosaccharide has 5 or 6 C atoms can form very

stable ring structures
This is achieved via an internal hemiacetal bond
Lets take D-ribose, there are 2 possibilities for ring closure:
C-1 with C-4 gives a 5-membered ring structure called furanose,
from the structure of the heterocyclic compound furan.
C-1 with C-5 gives a 6-membered ring structure called pyranose,
from the structure of the heterocyclic compound pyran.
In the cell 99% of pentoses and hexoses are in the ring
form: this equilibrium is highly favoured

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Formation of ring structures by pentoses.

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Preferences for ring structures
The preference between the furanose or pyranose

structures depends on:
The particular sugar
The pH
The solvent
The temperature
The specific structure where the sugar is incorporated:
For example, D-ribose is a ribofuranose in RNA but a
ribopyranose in polysaccharides

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AMP ADP
ATP
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Anomers and mutarotation
Cyclization creates a new asymmetric centre at
- anomer -anomer
C-1.
This is called anomeric carbon and generates
two possible forms called anomers.
The two possible configurations are:
The -anomer when the OH group in C-1 is
DOWN
The -anomer when the OH group in C-1 is UP
Anomerization occurs to the ribose sugar
moiety during de novo purine nucleotide
biosynthesis
The - and -anomer can inter-convert by
mutarotation
The ring structures are best represented by the
Haworth projections:
Bonds closer to the viewer are more dark to
suggest perspective
The Haworth projection is derived from the Fisher
projection by writing the atoms to the right of the
chain in Fisher below the ring in Haworth and vice
versa.

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-D-ribofuranose
conformational isomers:
C-1, O, C-4 define a plane;
A) C-2 is above the plane =
C-2 endo
B) C-3 is above the plane =
C-3 endo

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HEXOSES
The hexoses also exists primarily as ring structures (see previous table)
Also here we have the - and -anomers that can be interconverted by mutarotation and can be
represented with the Haworth projections:
Most common hexoses:
We can say hexoses prefer the pyranose ring structure, but here fructose is shown as furanose as it is
in its most common biological source: the disaccharide sucrose

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Conformational isomers
A pyranose, such as glucose,

has two common conformational
isomers:
The "boat" and "chair" form
These define the axial and
equatorial substituents
For glucose and most sugars)
the chair form is more stable
because the hydroxyls of
carbons 1 and 2 are further
removed and thus have less
steric interference with carbons
3, 4, and 5.
The pyranose ring in chair and boat conformations.

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In summary
Configurational isomers:
Interconversion requires
breakage of chemical
bonds
Conformational isomers:
Interconversion DOES
NOT requires breakage
of chemical bonds
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(CH2O)n with n > 6
They exists but have minor importance, except

sedoheptulose (7C) that is important for CO2
fixation in photosynthesis

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Monosaccharides: summary
Monosaccharide is another term for a simple sugar, such as glucose,

which is not linked to any other sugars.
Common monosaccharides include:
Glucose Mannose
Fructose Ribose
Galactose Erythrose
Monosaccharides may be called trioses, tetroses, pentoses, hexoses,
heptoses, or octoses, depending on whether they have 3, 4, 5, 6, 7, or 8
carbons, respectively, in them.
Monosaccharides containing an aldehyde group are called aldoses.
Monosaccharides containing a ketone group are called ketoses.
Monosaccharides that form five member rings are called furanoses.
Monosaccharides that form six member rings are called pyranoses.

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Derivatives of
monosaccharides
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Examples
They are obtained by substitution of OH groups:

1. Phosphate esters
2. Oxidations
Acids and lactones
3. Reductions
Alditols
4. Amino-sugars
5. Glycosides

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1. Phosphate
esters
We have already
seen AMP, ADP,
ATP, DNA, RNA;
Phosphate esters of
mnosaccharides are
key to metabolism

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Phosphorylation is key to metabolism;
Phosphate esters of monosaccharides participate to many
metabolic pathways;
They can be phosphorylated by ATP because their G is less negative
than - 31 kJ/mol (the G for ATP);
They can act as activated compounds
They exists as mixtures of monoanions and dianions under
physiological conditions, due to their 2 pKa in the regions of 1-2 and 6-
7.

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2. Oxidations: acids and
lactones
C-1 oxidations:
Mild oxidations of an aldose with alkaline Cu2+ - Fehling solution - produces aldonic
acids:
The red colour of Cu2O is a classic test for sugars in diabetics urins
Another test uses Ag+ that is reduced to Ag that gives a silver (Ag) coat in the test tube
The free aldonic acid gives an equilibrium with its lactone
C-6 oxidations:
These are common enzymatic reactions that give the uronic acid.
Uronic acids are typical of certain polysaccharides

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3. Reductions: alditols
Reduction of the carbonyl gives alditols:
Sorbitols accumulates in the lens of the eye of diabetic

people causing cataracts Prof. G. Gilardi - Biological Chemistry
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4. Amino-sugars
Very important because

there are the building
blocks of many
polysaccharides:

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Abbreviations
Structures need to be
abbreviated when writing
sugar polymers;
Example:
Man(1 4)GlcNAc(1 4)GlcNAc
(1 N)Asn

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5. Glycosides
Glycosidic bond:
Ether bond obtained by elimination of water between the anomeric
OH of a cyclic monosaccharide and the OH group of another
compound:
The resulting glycoside does NOT undergo mutarotation

spontaneously
Examples of 2 toxic glycosides: ouabain and amygdalin
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Ouabain
Ouabain is a glycoside poison that binds to and inhibits the action of the Na+/K+ pump in
the cell membrane. The Na+/K+ pump is essential for maintaining the balance of these
ions across cell walls.
Ouabain and digitoxin are used to stimulate the heart muscle. They work by binding to the
Na+/K+ ATPase and inhibiting its action. The result of this is that Na+ leaks back into the
cell. When this happens, the cell tries to maintain the osmotic balance pumping the sodium
out with the Na+/Ca2+ pump. This pumps Ca2+ into the cell, which triggers muscle
contraction.
It was discovered observing that Somali hunters dipped their harrow heads in extract from
an African shrub

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Amygdalin
Amygdalin is an O-linked glycoside found in the seeds of bitter

almonds.
Its poisonous nature results from the release of HCN upon
hydrolysis.
This is why HCN gas is said to have the odor of bitter almond
Amygdalin is commonly called Laetrile.

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Oligosaccharides
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Oligosaccharides
Glycosidic bonds between monosaccharides give rise to oligosaccharides and
polysaccharides.
Glycosidic bonds are formed by elimination of water between the anomeric hydroxyl of a cyclic
monosaccharide and the hydroxyl group of another compound.

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?

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Features of different disaccharides
Four features distinguish disaccharides from each other:

1. The two specific sugar monomers and their stereoconfigurations
Can be the same (2Glu for maltose) or different(Glu+Fru for sucrose)
2. The carbons involved in the linkage
Alaways involves C1 (reducing) + another:
C1-C1 threalose, C1-C2 sucrose, C1-C4 lactose, maltose, cellobiose, C1-C6 gentobiose (see fig)
3. The order of the monomeric units, if they are different kinds
Sugars can be reducing or non-reducing
Lactose: Gal has the C1 involved in the glycosidic bond so it is unreactive (non-reducing end), but
the Glu has the C1 free, hence it could react with the Fehling reagent (reducing end) to give aldonic
acid then lactone. Hence lactose is a reducing sugar and the Glu is the reducing end.
Sucrose: Glu has the C1 involved in the glycosidic bond with the C2 of Fru: there are no free CHO
groups, hence there is no reducing end (no reaction with Fehling reagent). Hence Sucrose is a non-
reducing sugar.
4. The anomeric configuration of the hydroxyl group on carbon 1 of each residue
This difference (see the 2 tables) is crucial to the shape of the polymer, hence the enzymes
that will be able to attack the oligosaccharide

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Writing the Structure of
Disaccharides
Abbreviations are used for the common monosaccharides.
The naming rules for oligosaccharides based on these abbreviations are as follows:
1. The sequence starts with the nonreducing end at the left using abbreviations
2. Anomeric and enantiomeric forms are designated by prefixes (e.g., , D-)
3. The ring configuration is designated by the suffixes p (pyranose) or f (furanose)
4. Numbers in parentheses between residue numbers are used to identify glycosidic bonds;
e.g., (1->4)
means a bond from carbon 1 of the residue on the left to carbon 4 of the residue on the right.
Thus:
-D-Glcp (12)--D-Fruf
corresponds to sucrose.

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Stability of the glycosidic bond
Oligosaccharides are formed by elimination of water between the anomeric

hydroxyl of a cyclic monosaccharide and the hydroxyl group of another
compound:
The G of hydrolysis is - 15 kJ/mol, so the equilibrium favours hydrolysis.

Nevertheless once the oligosaccharide is formed it remains stable and
enzymes are required for its hydrolysis
Oligosaccharides do not undergo mutarotation in the absence of an acid
catalyst, so they remain locked in the or configuration.

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Formation of the
glycosidic bond
Requires activated monomers

For example:
Lactase synthase = formation of milk
in mammary tissue
It requires Gal to the phosphorylated by
ATP
This is then transferred to UDP
The UDP-Gal transfers Gal to Glu
Cleavage of the phosphate bond
provides the energy necessary to form
Gal(14)Glc, that is lactose

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Disaccharides
Disaccharides are composed of two sugar residues. Examples include

sucrose, lactose, maltose, trehalose, and gentiobiose
Sucrose
disaccharide, composed of a glucose joined through
carbon 1 in linkage to carbon 2 of fructose.
Lactose
disaccharide composed of galactose and glucose
linked as follows: Carbon number one of galactose ( -
configuration) is linked to carbon four of glucose.

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Maltose and cellobiose
Maltose is a disaccharide of glucose

units joined -1,4.
It differs from cellobiose, which is also
a glucose disaccharide with units
joined -1,4.
The enzyme, maltase, catalyzes
hydrolysis of maltose to two molecules
of D-glucose
Cellobiose is a disaccharides of
glucose units joined in the -1,4
linkage.
The linkage between glucoses in
cellobiose is the same as that in the
cellulose polymer.

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Lactose
Lactose is a disaccharide composed of galactose and glucose linked as

follows: Carbon number one of galactose (-configuration) is linked to carbon
four of glucose. Lactose is formed as a result of the process.

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Outline of carbohydrates
Oligosaccharide Structures
Distinguishing features of Different Disaccharides
1. The 2 Specific Sugar Monomers Involved and their Stereoconfigurations.
2. The Carbons Involved in the Linkage.
3. The Order of the Two Monomer Units, if Different
4. The Anomeric Configuration of the OH Group on Carbon 1 of Each Residue
Writing the Structure of Disaccharides
1. Sequence written starting with the nonreducing end at the left.
2. Anomeric and enantiomeric forms are designated by prefixes.
3. The Ring Configuration is Indicated by a Suffix
4. The Atoms Between Which Glycosidic bonds are Formed are indicated by
Numbers in Parentheses Between Residue Designations.
Stability and formation of glycosidic bond.

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Polysaccharides
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Outline
Classification Glycoproteins
According to function N-Linked and O-Linked Glycoproteins
Storage p. N-Linked Glycans
Structural p. O-Linked Glycans
According to composition Blood Group Substances
Homopolysaccharides Oligosaccharides as Cell Markers
Heteropolysaccharides
Storage Polysaccharides
Amylose
Amylopectin
Glycogen
Structural Polysaccharides
Cellulose
Chitin
Glycosaminoglycans
The Proteoglycan Complex
Non-structural Roles of
Glycosaminoglycans
Bacterial Cell Wall Polysaccharides

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Polysaccharides
Polysaccharides are polymers of monosaccharide units

Functions:
Storage of sugars for energy:
Starch in plants
Glycogen in animals
Structural materials analogous to proteins:
Cellulose in plants
Chitin in animals
Structure:
Primary structure = sequence
Very simple, much simpler than proteins. Repeat of very very few (one or two) monosaccharide units
HOMOPOLYSACCHARIDES, for example cellulose = repeats of -D-glucose
HETEROPOLYSACCHARIDES, repeat of 2 or more monosaccharide units
Secondary structure = 3D structure
Usually very simple, extended, regular structures to form fibers or sheets
Exception: oligosaccharides present on cell surface and/or attached to glycoproteins = involved in recognition
processes, hence 3D structure deriving from primary sequence is important
In some cases, the monomeric units are modified monosaccharides.

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Polysaccharides containing a single sugar, such as glucose, are referred to as glucans.
Others, which contain only mannose, are called mannans. Still others, containing only
xylose, are called xylans.
Polysaccharides differ in:

the composition of the monomeric unit,
the linkages between them
the ways in which branches from the chains occur.
Common polymers, their monomeric units, and linkages/branches are :
Polysaccharide Name Monomeric Unit Linkages

Glycogen D-Glucose 1->6 branches
Cellulose D-Glucose 1->4
Chitin N-Acetyl-D-glucosamine 1->4
Amylopectin D-Glucose 1->6 branches
Amylose D-Glucose 1->4
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Storage polysaccharides:
Primary structure
Plants:
Starch (amido): amylose + amylopectin
Animals and bacteria:
Glycogen
Primary structure = sequence.
Amylose, amylopectin and glycogen are polymers of -D-glucopyranose
They are homopolysaccharides, glucans (glucose only)
They differ in the kind of linkages between the glucose units:
Amylose is linear, it only has (14) links between the Glc
Amylopectin is branched, it has both (14) and (16) links every 10-20
residues
Glycogen also is branched, it has both (14) and (16) links but more
frequent, every 8 residues
For this reason Glycogen is usually of higher MW

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Amylopectin and glycogen, branched glucans.
Note the non-reducing (N) and the reducing (R) ends. There are many N that are the sites of
enzymatic attack in case there an urgent need of mobilization of glucose (hence glycogen can give
even quicker mobilization) Prof. G. Gilardi - Biological Chemistry
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Storage polysaccharides:
Secondary structure
Amylose: the linear and regular primary structure
with (14) links allows the sugar to form helices
with 8 residues per turn
The structure was resolved using X-ray
crystallography
This linear configuration is best suited for long
term storage of Glc (only 1 non-reducing end
end)
One substance that will stabilize an amylose
helix is iodine (I2), which fits into the hollow core
of the structure.
Binding of iodine to amylose helices produces an
intense blue color and has long been used as a
qualitative test for starch
The branched structure of amylopectine and Structure of amylose.
glycogen does not allow the formation of helices
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Structural polysaccharides
Plants do not use fibrous proteins (keratin, collagen) for structural support
They synthesise polysaccharides instead:
Cellulose:
The most abundant biomaterial in the biosphere!
Like amylose is linear, but the bonds are (14)
This means that cellulose is a fully extended polymer, but with Glc units flipped by 180 with respect to its neighbors
The same small difference between cellulose and starch has another important consequence:
Animal enzymes that are able to catalyze the cleavage of the (14) link in starch cannot cleave cellulose.
For this reason, humans, even if starving, are unable to utilize the enormous quantities of glucose all around them in the form
of cellulose.
Ruminants such as cows can digest cellulose only because their digestive tracts contain symbiotic bacteria that produce the
necessary cellulases.
Termites manage to eat woody substances in a similar fashion-their guts harbor protozoans capable of cellulose digestion.
Many fungi also produce such enzymes, which is why some mushrooms can live on wood as a carbon source.

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Secondary structure of
structural polysaccharides
Cellulose has
extended chains;
The 180 flip allows H-
bonds to form in a
tight network;
It has a planar
structure;
It has crystalline
properties in some
parts of the fibers.
Structure of Cellulose .
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Organisation of
cellulose in the
plant cell wall

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Other components of the
fibers: hemicelluloses
Hemicelluloses
Xylans: polymers with (14) D-xylopyranose
Glucomannans

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Chitin: structural polysaccharide
Animals use both proteins and polysaccharides for

structural purposes
Chitin
Hetero-polymer of N-acetyl--
D-glucosamine
Its structures is basically the
same as that of cellulose,
except that C2 has a acetyl-
amino group
Found in fungi, some algae,
septum of diving yeast cells,
major material in exoskeleton
of mollusks and arthropodes

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Glycosaminoglycans or
mucopolysaccharides
In animals they have structural
Glycos-amino-glycans are and non-structural roles:
negatively charged Structural roles:
polysaccharides Connective tissue:

Composition:
Chondroitin sulfates and keratan
sulphates
Repeating disaccharide units Skin:

N-acetylglucosamine or N-
Dermatan sulphate, hyaluronic
acid
acetylgalattosamine, their Non-structural roles:
dervatives, Viscosity in synoviual fluids of
Sulfate or carboxylate groups
joints, vitreous humor of the eye
hyaluronic acid
(negatively charged) Anti-coagulant:
Heparin

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Proteoglycan complex
Proteoglycan complex: matrix that holds

together the skin and the connective tissue
Composition:
A filament, one single long hyaluronic acid
molecule
Core proteins are non-covalently attached to
it
Chondroitin sulfate and keratan sulphate are
covalently linked to the core proteins via Ser
side-chains
In cartilage, the negatively charged acidic
groups of the proteoglycan complex interatc
with the positively charged side chains in
collagen to form a tight and strong network

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Molecular composition.
(-6s means sulphate ester on C-6)
Repeating structures of some glycosaminoglycans.

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Si in biology
The proteoglycan complex is one of the rare cases

where Si enters in a biological matrix
There is 1 Si atom every 100 sugar monomers

Si forms bridges between adjacent sugars
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Heparin
Heparin is a heterogeneous polysaccharide polymer of D-iduronate-2-sulfate linked 1->4

to N-sulfo-D-glucosamine-6-sulfate.
Heparin fragment:
The sulfates in the molecule make it very negatively charged.

It strongly binds to anti-prothrombin III, and the complex inhibits enzyme of the blood
clotting process
Heparin is found in mast cells lining the walls of arteries. Heparin blocks blood clotting
and is used clinically for that purpose. In the body, release of heparin plays a role in
preventing a clot from becoming dangerously large.

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N-Acetylmuramic Acid
N-Acetylmuramic acid (MURNAc) is part of the peptidoglycan polymer of Gram-

positive bacterial cell walls. MURNAc is covalently linked to N-acetylglucosamine and
may also be linked through the hyroxyl on carbon number 4 to the carbon of L-
alanine (Figure 9.26). A pentapeptide composed of L-alanyl-d--isoglutaminyl-L-lysyl-
D-alanine-D-alanine is added to the MURNAc in the process of making the
peptidoglycan strands of the cell wall.

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Muramic Acid
Muramic acid is a modified monosaccharide found in glycoproteins and

peptidoglycans. An acetylated form of muramic acid, N-Acetylmuramic Acid, is a
component of the polysaccharide in the cell wall of Gram positive bacteria (see here).

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Polysaccharides in
Bacterial Cell Walls
The different structures of the cell walls of
Gram-positive and Gram-negative bacteria
provide the means of distinguishing them.
Gram-positive bacteria retain a dye-iodine
complex
This can be washed from Gram-negative
bacteria
The difference arises because
the cell walls in Gram-positive bacteria consist
of a cross-linked multilayered polysaccharide-
peptide complex called peptidoglycan,
layered on top of a lipid bilayer membrane
the cell walls in Gram-negative bacteria
consist of a single layer of peptidoglycan
sandwiched between outer and inner lipid
bilayer membranes.

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Gram positive
Gram negative

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Peptidoglycan
in Gram-positive
The long polysaccharide chains are
strictly alternating copolymers of
N-acetylglucosamine (NAG) and
N-acetylmuramic acid (NAM)
Cross-linked by an unusual
tetrapeptide attached to the lactic
acid moiety of the NAM : (L-Ala)-(D-
Glu)-(L-Lys)-(D-Ala)
The presence of the D-amino acids
and the unusual linkage of the
(Gly)5
glutamic acid through its -carboxyl
group may help protect the peptide
against protease action.
Individual peptides are cross-linked
together with a glycine pentapeptide
joining lysine through the NH2 group (Gly)5
and the COOH of adjacent Ala
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Linkage to the lipid layer
Done via Lipoteichoic acids

Lipid-oligosaccharide complexes called
lipoteichoic acids protrude from the
membrane through the peptidoglycan wall
D-Alanyl and NAG groups are arranged
irregularly on the chain that is then
anchored in the membrane by lipids

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Gram-negative
The peptidoglycal
layer is much thinner
It is sandwiched
between 2 lipid
membranes
The cross-links are
between NAM
residues with a simpler
tetra-peptide linked at
3-4 without Gly bridges
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Antibiotics
Cell wall assembly requires a battery of enzymes

Antibiotics are inhibitors of these enzymes, hence do not allow cell
wall assembly: this inhibits bacterial growth
Penicillin is an example:
It is an inhibitor of the trans-peptidase enzyme E required for the cross-linking
of the bacterial cell wall
Another type of antibiotics are enzymes that can attack the cell wall
itself:
Lysozyme is an example:
This enzyme catalyses the hydrolysis between GlcNAc and MurNAc residues.
This dissolves the cell wall, lyse the bacteria causing its death
Lysozyme is found in egg white, human tears and saliva

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Glycoproteins
76
Glycoproteins
More than half of all eukaryotic proteins carry covalently attached oligosaccharide or
polysaccharide chains (glycan).

77
N-linked and O-linked glycoproteins
Glycoproteins are classified as

N-linked glycoproteins
the glycans are usually attached through
N-acetylglucosamine or N-
acetylgalactosamine to the side chain
amino group in an asparagine (Asn)
residue.
A common sequence around the Asn
residue is -Asn-X-Ser/Thr-
O-linked glycoproteins
the glycans are usually attached through
an O-glycosidic bond between N-
acetylgalactosamine and the hydroxyl
group of a threonine (Thr) or serine
(Ser) residue

78
N-linked Glycans
There is a wide variety of N-linked oligosaccharide chains

A common sequence for N-linked glycans is :
Man(16)
Man(14)GlcNAc(14) GlcNAc(1N)Asn
Man(13)
This sequence is found in:
ovalbumin
Immunoglobulins (IgG - see table)
Every immunoglobulin has carbohydrate attached to the constant domain of each heavy chain.
Part of the recognition of immunoglobulins is due to the sequence of the oligosaccharide chains
of the glycans.
A very important further use of N-linked oligosaccharides is in intracellular
targeting in eukaryotic organisms:
Proteins destined for certain organelles or for excretion from the cell are marked
specifically by oligosaccharides during post-translational processing to ensure they
arrive at their proper destinations.

79
O-Linked Glycans
From the table it can be seen that O-linked glycans can assolve a variety of
functions:
Antarctic fish contain a glycoprotein that serves as an "antifreeze", preventing the
freezing of body fluids, even in extremely cold water
Mucins are found extensively in salivary secretions, contain many short O-linked
glycans. These glycoproteins increase the viscosity of the fluids in which they are
dissolved.
Some O-linked glycans appear to function in intracellular targeting and

molecular and cellular identification. An example is found in the blood group
antigens.

80
Blood group antigens
The blood group antigens are an

important group of
oligosaccharides
They can be linked to
Membrane proteins via a O-linked
glycan
Lipid molecule to form a glycolipid
In both cases they are anchored to
the membrane

81
ABO blood types
The O oligosaccharide elicit antibodies in most

humans
The A and B antigens are formed by addition
of GalNAc (A) or Gal (B) to the O
oligosaccharide
This requires an additional enzyme
Some individuals are heterozygous and can
produce both antigens (AB)
Each of the A and B antigen can elicit a
specific antibody

82
Transfusion relationships

83
Oligosaccharides as Cell Markers
Molecules of the blood group antigens represent only a special case of a much more general phenomenon - cell
marking by oligosaccharides.
In multicellular organisms, different kinds of cells must be marked on their surfaces so that they can interact properly
with other cells and molecules. The surface of many cells are nearly covered with polysaccharides, which are attached
to either proteins or lipids in the cell membrane. Some animal cells have an extremely thick coating of polysaccharides
called a glycocalyx.

84
For oligosaccharides or polysaccharides to serve as recognition signals, there
must be proteins that bind to them specifically.
One such class is the immunoglobulins.
Another very diverse group of saccharide-binding proteins is the lectins.
In plants, lectins appear to play defensive roles and aid in adhering nitrogen-fixing
bacteria to roots. In animals, lectins seem to be involved in interactions between cells
and proteins of the intercellular matrix, such as collagen, and help to maintain tissue
and organ structure.
The cell surfaces of many cancer cells are abnormal, which may account for the
loss in tissue specificity that such cells commonly exhibit.
Properties of oligosaccharides that aid in their role as cellular markers:
They can present a wide variety of structures in relatively short chains.
The multiple possible monomers, linkages, and branching patterns allow a vast, but
specific vocabulary.
They are very potent antigens (antibodies can be elicited swiftly against them)

85
Antibodies
86
87
88
89
Schematic models of an antibody molecule and a Fab fragment.
90
91
92
Possible questions
1. Predendendo come esempio le formule di due monosaccaridi di tua

scelta, spiegare con luso di formule e diagrammi tutti i tipi di isomeria
di configurazione e conformazione dei monosaccaridi.
2. Descrivi i derivati dei monosaccardi ottenuti per:
a) Esteri con il fostato
b) Ossidazioni
c) Riduzioni
d) Aminozuccheri
e) Glicosidi
3. Descrivi il legame glicosidico, la sua struttura ed elementi di stabilita
4. Prendi due esempi di disaccardi con legame alfa e due con legame
beta, e discuti la differenza tra i due tipi di legame.

93
1. Descrivere i livelli di struttura e organizzazione dei
polisaccaridi
2. Descrivere il ruolo stutturale dei polisaccaridi nel cell wall
delle cellule vegetali
3. Descrivere lorganizzazione dei polisaccaridi nel cell wall
batterico, e il loro ruolo nella classificazione Gram
negativi e positivi
4. Descrivi in termini molecolari i vari ruoli fisiologici svolti
dalle glicoproteine.
5. Descrivere con luso di formule i legami dei glicidi con le
proteine nelle glicoproteine e fare un esempio funzionale
di questa classe di proteine
6. Descrivere la struttura e funzione degli anticorpi

94

6 Carbohydrates

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6 Carbohydrates

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6.

Saccharide is another name for a carbohydrate.

Saccharides play a variety of roles in living organisms:

Monosaccharides are the simplest sugars, having the formula

Monosaccharides can be categorized according to their value of

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

D- glyceraldehyde and dihydroxyacetone are also TAUTOMERS = structural

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

The predominant monosaccharides found in nature have

Stereochemistry of aldo-tetroses: Stereochemistry of keto-tetroses:

Prof. G. Gilardi - Biological Chemistry

When a monosaccharide has 5 or 6 C atoms can form very

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

The preference between the furanose or pyranose

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

Most common hexoses:

Prof. G. Gilardi - Biological Chemistry

A pyranose, such as glucose,

The pyranose ring in chair and boat conformations.

They exists but have minor importance, except

Prof. G. Gilardi - Biological Chemistry

Monosaccharide is another term for a simple sugar, such as glucose,

Prof. G. Gilardi - Biological Chemistry

They are obtained by substitution of OH groups:

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

Reduction of the carbonyl gives alditols:

Sorbitols accumulates in the lens of the eye of diabetic

Very important because

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

The resulting glycoside does NOT undergo mutarotation

Prof. G. Gilardi - Biological Chemistry

Amygdalin is an O-linked glycoside found in the seeds of bitter

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

Four features distinguish disaccharides from each other:

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

Oligosaccharides are formed by elimination of water between the anomeric

The G of hydrolysis is - 15 kJ/mol, so the equilibrium favours hydrolysis.

Prof. G. Gilardi - Biological Chemistry

Requires activated monomers

Prof. G. Gilardi - Biological Chemistry

Disaccharides are composed of two sugar residues. Examples include

Prof. G. Gilardi - Biological Chemistry

Maltose is a disaccharide of glucose

Prof. G. Gilardi - Biological Chemistry

Lactose is a disaccharide composed of galactose and glucose linked as

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

Prof. G. Gilardi - Biological Chemistry

Polysaccharides are polymers of monosaccharide units

Prof. G. Gilardi - Biological Chemistry

Polysaccharides differ in: