Carbohydrate

Chemistry
Dr. Thomas B. Nyambo
Department of Biochemistry
School of Medicine
MUCHS
1 October 2004
 Carbohydrates
The generic term carbohydrate includes
monosaccharides, oligosaccharides and
polysaccharides as well as substances derived from
monosaccharides by reduction of the carbonyl
group (alditols), by oxidation of one or more
terminal groups to carboxylic acids, or by
replacement of one or more hydroxy group(s) by a
hydrogen atom, an amino group, a thiol group or
similar heteroatomic groups.
It also includes derivatives of these compounds.
The term 'sugar' is frequently applied to
monosaccharides and lower oligosaccharides.
their general formulas can all be written in a
simple form as (CH2O)x. (hydrated form of carbon).
Another term used to describe sugar-based
molecules is rooted in the word saccharide from the
Latin, saccharum, meaning sugar. Sugars can be
defined as polyhydroxy aldehydes or ketones
 Monosaccharide Nomenclature
Parent monosaccharides are polyhydroxy
aldehydes H-[CHOH]n-CHO or polyhydroxy
ketones H-[CHOH]n-CO-[CHOH]m-H with three or
more carbon atoms.
The generic term monosaccharide,as opposed to
oligosaccharide or polysaccharide denotes a
single unit, without glycosidic connection to other
such units. It includes aldoses, dialdoses,
aldoketoses, ketoses and diketoses, as well as
deoxy sugars and amino sugars, and their
derivatives, provided that the parent compound
has a potential carbonyl group.
Monosaccarides are the simplest sugars, having
the formula (CH2O)n. The smallest molecules
usually considered to be monosaccharides are
those with n = 3.
C 3 Triose,C4Tetrose C5 Pentose,C 6 Hexose, C7
Heptose, C8 Octose.
 Terms Definition
Isomers are chemical substances with the same
chemical formular but different structure
Diastereomers have opposite configuration at one or
more carbons, but not at all asymmetric carbons, so
are not mirror images
Epimers have only one carbon of a different
configuration and are a special case of diastereomers
Anomers differ at the anomeric carbon
Optical isomers are compounds with the same
molecular formula but differ in the way they rotate
plane polarized light. There are two kinds of optical
isomers. One type of optical isomer are compounds
that are mirror images of one another but can't be
superimposed on each other. These isomers are called
enantiomers and are said to be optically active
 Isomers
Sugars can exists as either configurational
isomers (interconverted only by breaking
covalent bonds) and conformational isomers.
 Isomers

.
 Nomenclature
Monosaccharides can exist as aldehydes or
ketones and are called aldoses or ketoses,
respectively.
For example (C3) glyceraldehyde an aldo-
triose, and dihydroxyacetone, a keto-triose.
Glyceraldehyde and dihydroxyacetone have the
same atomic composition, but differ only in the
position of the hydrogens and double bonds.
Moreover, they can interconvert via an enediol
intermediate. When the structures of molecules
are related in these ways, the molecules are
called tautomers
 Isomerism

.
Tautomerism (Aldose-ketose interconversion via an enediol intermediate)

.
Stereochemical relationships of the D-aldoses
Intramolecular hemiacetals or hemiketals
The aldehyde and ketone moieties of the
carbohydrates with five and six carbons will
spontaneously react with alcohol groups present
in neighboring carbons to produce
intramolecular hemiacetals or hemiketals,
respectively.
This results in the formation of five- or six-
membered rings. Because the five-membered
ring structure resembles the organic molecule
furan, derivatives with this structure are termed
furanoses.
Those with six-membered rings resemble the
organic molecule pyran and are termed
pyranoses.
Such structures can be depicted by either
Fischer or Haworth style diagrams.
 Nomenclature
Carbons in a monosaccharide are
numbered such that the aldehyde group is
carbon number one or the ketone group is
carbon number two.
The three dimensional arrangement of
atoms around a carbon atom are such that
if four different groups are attached to it,
they can be arranged in two different
ways. Such a carbon is described as chiral
or asymmetric.
The two molecules with different three-
dimensional arrangement are mirror
images of each other, and the two
different forms are called stereoisomers.
For example, D-glyceraldehyde and L-
glyceraldehyde are mirror images of each
other (stereoisomers) and cannot be
Naming the carbon atoms of D-glucose

.
The enantiomers of glyceraldehyde
.
 Nomenclature
Such molecules with these properties are called
enantiomers.
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, however, because it depends
on the reference compound chosen.
Sugars with more than one asymmetric carbon
have many possible three dimensional
configurations.
A molecule with n chiral centers will have 2n
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
 Structures of Glyceraldehyde Enantiomers

A C-atom that is linked to four different groups as glyceraldehyde is, is called

asymmetric. Such asymmetrically substituted carbon atoms are optically
active, i.e. they shift the plane of polarized light. The angle of the shift is
specific for the substance. D-glyceraldehyde shifts the plane to the right (+),
L-glyceraldehyde (-) to the left.
 Structures of Glyceraldehyde Enantiomers

.
 D and L Glucose

.
 Intramolecular reactions
An aldehyde can react with an alcohol to form a
hemiacetal.
Similarly a ketone can react with an alcohol to

form a hemiketal.
 NomencIature
When sugars cyclize, they form furanose
or pyranose structures .
These are molecules with five-membered
or six-membered rings, respectively.
Cyclization creates a carbon with two
possible orientations of the hydroxyl
around it.
This carbon is referred as the anomeric
carbon and the two possible forms as
anomers. The two possible configurations
of the hydroxyl group are called and ,
which correspond to the hydroxyl being in
the "down" and "up" positions,
respectively, in standard projections
 Fischer projection

.
 Pyranose and furanose rings
Glucose, an aldo-hexose, is a central sugar in
metabolism.
Glucose and other 5 and 6C sugars can cyclize
through intramolecular nucleophilic attack of
one of the OH's on the carbonyl C of the
aldehyde or ketone. Such intramolecular
reactions occur if stable 5 or 6 member rings
can form.
The resulting rings are labeled furanose (5
member) or pyranose (6 member) based on
their similarity to furan and pyran.
On nucleophilic attack to form the ring, the
carbonyl Oxygen becomes an OH which points
either below the ring ( anomer) or above the
ring ( anomer).
Cyclic Fischer and Haworth Projection of -D-Glucose

.
 Pyranose and furanose rings

.
 Pyranose and furanose rings
Monosaccharides in solution exist as
equilbrium mixtures of the straight and
cyclic forms.
In solution, glucose (Glc) is mostly in the
pyranose form , fructose is 67% pyranose
and 33% furanose, and ribose is 75%
furanose and 25% pyranose.
However, in polysaccharides, Glc is
exclusively pyranose and fructose and
ribose are furanoses.
 Haworth projections.

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
 The chair form and the boat form.
The spatial relationships of the
atoms of the furanose and pyranose
ring structures are more correctly
described by the chair form and the
boat form.
Constituents of the ring that project
above or below the plane of the ring
are axial and those that project
parallel to the plane are equatorial.
In the chair conformation, the
orientation of the hydroxyl group
about the anomeric carbon of -D-
glucose is axial and equatorial in -
D-glucose.
 Chair and boat conformations of Glucose

.
 Chair form of a-D-Glucose

.
 Mutarotation
Carbohydrates can change
spontaneously between the and
configurations, a process known as
mutarotation.At equilibrium Glucose
is two thirds and Glucose is one
third.
 -D glucose
Glucose has an anomeric carbon, which can exist in the
and configurations. Glucose can exist in both the
D and L forms (though the D-form predominates
biologically).
It can exist as a straight chain or in ring structures
composed of 5 (furanose) or 6 (pyranose) member
rings.
Optical rotation
Rotation of polarised light
If the sign of the optical rotation under specified
conditions is to be indicated, this is done by adding (+)-
for dextro or (-)- for levo before the configurational
prefix. Racemic forms are indicated by ()-.
Examples:
D-Glucose or (+)-D-glucose
D-Fructose or (-)-D-fructose
DL-Glucose or ()-glucose
-D glucose -D galactose and -D Mannose
 Ribose sugars

.
 Monosaccharide Derivatives
Many derivatives of monosaccharides are found in nature. These
include:
oxidized forms in which the aldehyde and/or alcohol functional
groups are oxidized to carboxylic acids
phosporylated forms in which phosphate is added by ATP to form
phosphoester derivatives
amine derivatives such as glucosamine or galactosamine
acetylated amine derivatives such as N-Acetyl-GlcNAc (GlcNAc) or
GalNAc
lactone forms (intramolecular esters) in which an OH group
attacks a carbony C that was previously oxidized to a carboxylic
acid
condensation products of sugar derivatives with lactate
(CH3CHOHCO2-) and pyruvate, (CH3COCO2- ), both from the
glycolytic pathway, to form muramic acid and neuraminic acids,
(also called sialic acids), respectively.
 Derived sugars: alcohol, amine and acidic
sugars.

.
 Ascorbic acid

.
 Phosphorylated sugars

.
 Disaccharides

.
 Disaccharides: (-(1,2) and (1,4) glycosidic bond in sucrose and
lactose respectively

.
 Reducing sugars
The aldehyde group is susceptible to oxidation
by reagents (Benedicts Solution - with citrate,
Fehlings reagent - with tartrate) which are
subsequently reduced.
In both reagents, reducing sugars reduce a
basic blue solution of CuSO4 (Cu2+) to form a
brick red precipate of Cu2O (Cu+).
Sugars such as monosaccharides,
dissacharides and polysaccharides which can
form an aldehyde at C1 or have an -
hydroxymethyl ketone group which can
isomerize to an aldehyde under basic conditions
such as fructose are called reducing sugars.
These oxidizing agent are mild and react with
aldehydes and not ketones.
 Lactose and Sucrose
lactose: Gal( 14)Glc Since Glucose
is attached to Galactose through the OH
on C4, its anomeric carbon, C1, could
revert to the noncyclic aldehyde form and
hence lactose is a reducing sugar.
sucrose: Glc(12)Fru. Since Fructose is
attached through the anomeric OH of this
ketose, the Fru is not in equilibrium with
its straight chain keto form, and hence
sucrose is a nonreducing sugar.
 Polysaccharides
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
 Storage polysaccharides
Glycogen
Glycogen is the major form of stored carbohydrate
in animals. This crucial molecule is a homopolymer
of glucose in -(1,4) linkage; it is also highly
branched, with -(1,6) branch linkages occurring
every 8-10 residues. Glycogen is a very compact
structure that results from the coiling of the
polymer chains. This compactness allows large
amounts of carbon energy to be stored in a small
volume, with little effect on cellular osmolarity
Starch
Starch is the major form of stored carbohydrate in
plant cells. Its structure is identical to glycogen,
except for a much lower degree of branching
(about every 20-30 residues). Unbranched starch
is called amylose; branched starch is called
amylopectin.
 Storage form of glucose in yeast and bacteria
Dextran
Has mainly 1 6 linkages

Is the storage form of glucose in yeast

and bacteria
It is a component of dental plaque.

After further chemical cross-linking,

dextran becomes Sephadex, or other
similar compounds, used in the
laboratory to form sizing gels.
 Polysaccharides

.
 Polysaccharides
Amylopectin is a glucose polymer with mainly
(1 4) linkages, but it also has branches formed by
(1 6) linkages. The branches are generally longer
than shown above.
Glycogen, the glucose storage polymer in animals, is
similar in structure to amylopectin. But glycogen has
more a(1 6) branches.
Cellulose, a major constituent of plant cell walls,
consists of long linear chains of glucose, with (1 4)
linkages. Every other glucose in cellulose is flipped over,
due to the linkages. This promotes intrachain and
interchain hydrogen bonds, as well as van der Waals
interactions, that cause cellulose chains to be straight
and rigid, and pack with a crystalline arrangement in
thick bundles called microfibrils.
 Structural polysaccharides
The -1,4-linked glucose units of amylose are
bent which is why amylose forms a helical
structure
If the linkages are changed to -1,4-linkages
the linear cellulose polysaccharide results.
Cellulose has great strength in the wood of
trees due to the possibility of interconnecting
hydrogen bonds
But cellulose is also delicate as cotton fibers.
Only ruminant animals and insects like termites
can digest wood because they posses cellulase
enzyme secreted by the symbiotic bacteria they
host.
Secondary structure of amylose.
.
Amylopectin, a branched glucan
.
 Planer secondary structure of
cellulose
.
 Digestion
Linkages between the individual units
require special enzymes to break
them down.
For example, the 1-> 4 linkages
between glucose units in glycogen,
amylose, and amylopectin, are readily
broken down by all animals.
But only ruminant animals (cows,
horses, etc.) contain symbiotic
bacteria with an enzyme (cellulase)
that can break down the 1-> 4
linkages between individual glucose
units in cellulose.
As a result our dietary cellulose is
unavailable as an energy source and
act as roughage.
 Function of polysaccharides
Polysaccharides are used to some extent for
energy storage in almost all higher organisms.
Animals use glycogen. Plants use starch, which is
composed of amylose and amylopectin.
These polysaccharides are used for energy
storage: are readily broken down into monomeric
units that can be rapily metabolized to produce
ATP.
In addition to polysaccharides used for energy
storage
Plants use polysaccharides, such as cellulose, for
structural purposes in their cell walls.
The exoskeleton of many arthropods and
mollusks is composed of chitin, a polysaccharide
of N-acetyl-D-glucosamine.
 Glycosaminoglycans
Glycosaminoglycans are polysaccharides
containing alternating residues of uronic
acid and amine derivatives of hexoses
(such as N-acetylglucosamine).
Typically the repeating unit carries a
carboxyl group and often one or more
sulfates, so that most glycosaminoglycans
have a high density of negative charges.
Glycosaminoglycans are often combined
with protein to form proteoglycans and are
an important component of the
extracellular matrix of vertebrates.
Glycosaminoglycans provide structural
support in vertebrates
 Proteoglycans
When covalently linked to specific core
proteins, glycosaminoglycans form complexes
called proteoglycans.
Some proteoglycans of the extracellular matrix
in turn link non-covalently to hyaluronate via
protein domains called link modules. For
example, in cartilage multiple copies of the
aggrecan proteoglycan bind to an extended
hyaluronate backbone to form a large complex
Versican, another proteoglycan that binds to
hyaluronate, is in the extracellular matrix of
loose connective tissues.
 Glycosaminoglycans
Several glycosaminoglycans are
listed below:
Chondroitin sulfates, Hyaluronic

Acid ,Keratan
sulphate,Heparin,Dermatan
sulphate,peptidoglycans
Monomeric units of glycosaminoglycans
 N-Acetyl- -D-glucosamine
N-Acetyl- -D-glucosamine is the
monomeric unit of chitin.
It is also part of the peptidoglycan
polymer of Gram-positive bacterial cell
walls.
It is also a component of hyaluronic acid
in conjunction with glucuronic acid.
N-Acetyl- -D-glucosamine is also a
component of the ABO blood group
antigens
Hyaluronic acid is a heteropolymer of alternating units of
glucuronic acid and N-acetylglucosamine.
 Repeating structures of some glycosaminoglycans

.
 Heparan sulfate and Heparin

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 a sulfated sugar called
iduronic acid, while N-acetylglucosamine residues may be
deacetylated and/or sulfated
Heparin, a glycosaminoglycan found in granules of mast cells, has a
 Chondroitin Sulfates
Chondroitin sulfates are molecules classified as
glycosaminoglycans.
Two common chondroitin sulfates are chondroitin-4-
sulfate and chondroitin-6-sulfate. Each is a polymer of
alternating units of D-glucuronate and N-acetyl-D-
galactosamine-sulfate linked in a 1-3 linkage. The
only differences between the polymers is the sulfate
positions.
Core proteins in cartilage have chondroitin sulfate and
keratan sulfate chains covalently bound to them
through serine side chains.
In cartilage, this kind of structure binds collagen and
helps hold the collagen fibers in a tight, strong network.
The binding involves electrostatic interactions between
the sulfate and/or carboxylate groups of the
proteoglycan complex and the basic side chains in
collagen.
Bacterial cell wall
 Glycoproteins
More than half of all eukaryotic proteins carry
covalently attached oligosaccharide or
polysaccharide chains.
Glycoproteins differ from proteoglycans in that
proteoglycans are preodominantly composed of
glycosamino-glycan polysaccharides connected to
extended core polypeptides, forming huge feathery
molecules.
Glycoproteins are classified as N-linked or O-linked in
two groups In N-linked glycoproteins, the glycans are
usually attached through N-acetylglucosamine or N-
acetylgalactosamine to the side chain amino group in
an asparagine residue.
In O-linked glycoproteins, glycans are usually attached
through an O-glycosidic bond between N-
acetylgalactosamine and the hydroxyl group of a
threonine or serine residue.
 Glycoproteins
N-linked Glycans
Important N-linked glycans are found in
ovalbumin and the immunoglobulins. A very
important further use of N-linked
oligosaccharides is in intracellular targeting in
eukaryotic organisms. O-Linked Glycans
Mucins, which 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
Antarctic fish contain a glycoprotein that serves
as an "antifreeze", preventing the freezing of
body fluids, even in extremely cold water.
 O and N linked glycans
.
 QUIZ
1.The molecular formula for glucose is C6H12O6. What would be the
molecular formula for a polymer made by linking ten glucose molecules
together by dehydration synthesis?
A)C60H120O60.
B)C6H12O6)10.
C)C60H102O51.
D)C60H100O50.
D) None of the above.
2. Monosaccharides, such as ribose, fructose, glucose, and mannose differ
significantly in
A) their sweetness.
B) the positions of their carbonyl groups.
c) their diastereomeric configurations.
D) their number of carbon atoms.
C) All but the first choice are significant differences.
3. Boat and chair conformations are found
A) in pyranose sugars.
B) in furanose sugars.
C) in any sugar without axial -OH groups.
D) in any sugar without equatorial -OH groups.
E) only in a-D-glucopyranose.
 QUIZ
4. Which of the following is an example of a storage polysaccharide made by animals?
A) cellulose.
B) glycogen.
C) collagen.
D) amylopectin.
E) starch.
5. Cellulose, a (1->4)-linked glucose polysaccharide, differs from starch in that starch
is
A) (1->6)-linked manose polysaccharide
B) a (1->6)-linked glucose polysaccharide.
C) an (1->6)-linked glucose polysaccharide.
D) an (1->4)-linked glucose polysaccharide.
E) an (1->4)-linked mannose polysaccharide.
6. The glycosidic bond
A) joins glucose and fructose to form sucrose.
B) in sucrose is hydrolyzed by bees to make honey from nectar.
C) in maltose is not hydrolyzed in "lactose intolerant" humans.
D) in lactose is hydrolyzed by human infants to make two galactose monosaccharides.
E) The first two choices are both correct.
7. Cellulose fibers resemble ___ in proteins; whereas -amylose is similar to ___.
A) -helices; -sheets.
B) -sheets; -helices.
C) -sheets; the hydrophobic core.
D) -helices; -turns.
E) -turns; coiled-coils.