Lecture 9 Page 1
Lecture 9: Carbohydrate structure.
Properties we already know about commonly encountered sugars:
The most common sugar most people encounter is sucrose. Properties of sugar are you already
familiar with:
1. It is sweet. Interestingly not all carbohydrates are sweet. Taste glucose and you will find it to
be fairly boring. Fructose, the major sugar in honey is incredibly sweet. Sucrose, commonly
known as sugar, contains glucose and fructose and is also sweet. Fructose is supposed to be
~8X sweeter than sucrose. Maybe another reason why they include sucrase in chocolates.
2. It is very soluble in water. Think how much sugar you can put in your tea if you wanted to.
You can make up 2 M sucrose solutions with relative ease. It is very thick though. Try making
toffees. You dissolve 3 cups of sugar in 1 cup of water.
The hydrophilic nature of sugar ie. its solubility is due in part to all the hydroxyls, as we saw in the
structures in the last lecture. Sugars are found as part of many biological molecules, both
macromolecules and many cofactors. For example DNA and RNA both contain sugar in the backbone
of the polymer. This repeating sugar-phosphate backbone makes the outside of the DNA double helix
hydrophilic and protects the hydrophobic bases. ATP, NAD and a host of other cofactors all contain
ribose which does make them more soluble in aqueous media. Bases, such as adenine and
nicotinamide by themselves are quite hydrophobic. Carbohydrates are often attached to proteins,
forming glycoproteins. These glycoproteins are often found on cell surfaces as antigens or receptors.
Lipids and carbohydrate also combine forming lipopolysaccharides. These are also often found on
the cell surfaces, particularly of bacteria. They become the antigens for the immune response. Part of
the role of carbohydrates on proteins and lipids maybe solubility in various locations.
Carbohydrates are the most abundant class of organic molecule so we had better find out something
about the chemistry of them. They appear in so many other significant biomolecules.
Consider glucose, the quintessential sugar:
Glucose, is a high energy compound. The complete oxidation of 1 mole of glucose to 6CO2 yields
2870 kJ of energy. In cells this is trapped as lots of ATP (somewhere around 30).
It is vitally important that blood glucose levels be kept at ~5 mM. Why?
Glucose is a reducing sugar - this an old term that many of you may have heard of.
Let’s consider the basic monosaccharides.
They have a carbon chain of between 3 and 7 carbons and have names like trioses (3C), tetroses (4C),
pentoses (5C), hexoses (6C0, heptoses (7C).
Lecture 9 Page 2
BUT the really important bit about monosaccharide structure is the =O. This can be a keto group 
ketoses or an aldehyde group  aldoses.
CHO
CH 2OH
H
C
OH
HO
C
H
H
C
H
C
C
O
HO
C
H
OH
H
C
OH
OH
H
C
OH
CH 2OH
CH 2OH
D-glucose aldose
D-Fructose ketose
Numbering the carbons:
The carbons on glucose are numbered from the aldehyde group (referred to as C-1). The carbons on
fructose are numbered similarly, thus the keto group is attached to carbon 2. While this numbering
may seem academic and bordering on the pedantic it is very important when you use radioactive
isotopes. If you wish to have a 14C label on a particular carbon you specify the carbon by this
numbering system. Later on when we examine the metabolic fate of glucose you will find certain
carbons in the glucose skeleton have particular fates. This numbering unambiguously specifies which
carbon we are talking about. BE FAMILIAR WITH IT!!
1
CHO
H
2
HO
3
H
4
H
5
C
C
C
C
1
CH 2OH
OH
H
2
O
C
C
HO
3
H
H
4
OH
H
5
OH
OH
OH
6
CH 2OH
C
C
6
CH 2OH
D-glucose aldose
Numbering of sugars
D-Fructose ketose
Lecture 9 Page 3
The stereochemistry of carbohydrates.
The internal carbons –HCOH- are chiral. If you take glucose there are 4 chiral carbons. Each has 2
possible isomeric forms so you have 16 different stereoisomers of an aldohexose; 8 D-isomers and 8
L-isomers. D-Glucose, the universal SUGAR OF LIFE, is just one of them.
The D and L convention is based on the Fischer Projection of the molecule relative to glyceraldehyde,
which must be an important molecule if they keep referring to it.
Some terms for the spatially challenged:
Stereoisomers are molecules with the same formula but different spacial arrangements. Within this
there are some sub-groups. Stereoisomers that are mirror images of each other are called
enantiomers. Stereoisomers that are not mirror images (differ in configuration about more than one
chiral carbon) are called diastereomers. Two sugars that differ in their configuration about one
carbon are called epimers. Galactose is an epimer of glucose. Mannose is also an epimer of glucose.
However, galactose is not an epimer of mannose, they are diastereomers. To convert galactose to
glucose requires a complicated set of reactions involving epimerases.
The cyclisation of monosaccharides:
This bit is really important and underpins a lot of the structures that contain sugars. In solution,
glucose and other sugars cyclise to form ring structures. Alcohols readily and reversibly react with
aldehydes to form hemiacetals. In the case of monosaccharides the aldehyde reacts with a hydroxyl on
the same structure. The rings formed are usually 5 or 6 membered rings. 6 membered rings are similar
to a compound called pyran and such sugars are known as pyranoses. 5 membered rings are known as
furanoses as they are similar to a compound called furan. Alcohols also react with keto groups to
form hemiketals.
O
pyran
O
furan
Lecture 9 Page 4
Carbohydrate rings are often drawn as a Haworth projection. The 5 or 6 membered ring lays
perpendicular to the plane of the paper with the thick, bold lines representing the side closest to the
reader.
CH 2OH
CH 2OH
O
OH
OH
O
OH
OH
CH 2OH
OH
OH
OH
beta-D-glucose
beta-D-fructose
As the ring forms, the hydroxyl (which was the derived from the O of the aldehyde or keto) can end
up above or below the ring. If the –OH ends up above the ring it is called beta, if it ends up below the
ring it is alpha. The carbon with the =O attached is called the anomeric carbon. In the case of glucose
this is carbon 1. In the case of fructose it is carbon 2. What makes this anomeric carbon so important
(hence why we give it a name and you have to learn it) is that the configuration about this carbon
changes in solution. Glucose is in equilibrium in solution between the alpha form  the open chain
form and the beta form. To convert from the alpha form to the beta form does not require an enzyme.
Glucose is most stable in the beta form, probably because the –OHs (the bulky side chains) are lying
equatorial to the plane of the ring.
CHO
H OH
H
H O
HO
HO
HO
H
H
D-glucose
OH
H
H
OH
OH
H
OH
H
OH
CH 2OH
H OH
H O
HO
HO
OH
H
OH
H
H
D-glucose
Sugar Tests:
A sugar with a free anomeric carbon, (which allows the transient formation of the aldehyde species
in solution), such as glucose, is capable of reducing H2O2, ferricyanide, some metal ions (Cu2+, Ag+)
and other reagents. This is the basis of Fehling’s test and explains the term reducing sugar. In
Fehling’s test the aldehyde reduces the Cu2+ ions in an alkaline environment to form Cu2O and is itself
oxidized to a carboxylic acid (gluconic acid in the case of glucose). The Cu2O is red and precipitates.
Lecture 9 Page 5
Benedict’s test and Tollen’s test involve the reduction of Ag+ and precipitation of Ag metal by
reducing sugars, producing a silver mirror. The aldehyde group again is oxidized to a carboxylic acid.
Glucose is now usually measured enzymatically, using glucose oxidase.
There are a number of tests for other sugars which are based on the formation of a furfural derivative,
in strong mineral acids by dehydration. These derivatives then condense with specific phenolic
compounds to produce coloured derivatives. The coloured products form the basis of many qualitative
and quantitative sugar tests. Examples include the diphenylamine reaction (which is specific for DNA,
not RNA), the orcinol test (which distinguishes RNA from DNA) and resorcinol (Seliwanoff reagent)
for fructose.
The aldehyde group also makes glucose quite dangerous to have in your body at high concentrations
for long periods of time. Hence your body has elaborate mechanisms for maintaining the [glucose] blood
constant at ~5 mM. If the concentration increases too much for too long the glucose starts reacting
with proteins in your arteries. A measure of the management of diabetes is the glycosylation of
hemoglobin. Some of the nastier symptoms of diabetes can be attributed to glucosylated proteins in
the cornea (blindness) and arteries (circulation problems).
Other important things about the ring structures.
The rings are not planar like aromatic rings and the bases in nucleotides. There are no conjugated
double bonds and the sugar rings do not absorb ~260 – 280 nm.
The rings are not rigid and can exist in a number of puckered conformations, the most favoured being
the chair form (shown below) and the boat form.
H OH
H O
HO
HO
H
H
H
OH
OH
D-glucose
Common Dissacharides
Sucrose is a disaccharide of fructose and glucose. The glycosidic bond that joins the two
monosaccharides attaches from the carbon 1 of glucose in the alpha orientation to carbon 2 of
fructose, hence it is written as glucose--1,2-fructose. Note that the anomeric carbon of glucose (C1)
and the anomeric carbon of fructose (C2) are not free to uncyclise and reform. Sucrose is no longer a
reducing sugar.
Lecture 9 Page 6
CH2OH
CH2OH
O
H
H
O
OH
OH
CH2OH
O
OH
OH
OH
sucrose
Lactose, (D-galactosyl:14-D-glucose) found in milk, is a disaccharide of galactose (an epimer of
glucose which differs from glucose in its conformation about C4) and glucose.
CH 2OH
CH 2OH
O
OH
O
O
OH
H
reducing end
OH
H
OH
OH
OH
glucose
galactose
lactose
Maltose (:1 4 glucose) is the disaccharide of 2 glucose units joined from C1 to C4. It contains a
reducing end.
CH 2OH
CH 2OH
O
O
H
reducing end
OH
OH
OH
O
OH
OH
OH
glucose
glucose
maltose
Lecture 9 Page 7
Starch and glycogen consist of repeating units of maltose joined by :14 linkages with :16
branch points. There are different types of starch based on the number of branch points. Amylose, the
unbranched form assumes a helical conformation in solution. Iodine fits nicely into the middle of this
helix resulting in a strong blue coloured complex, the basis of the iodine starch test.
CH 2OH
H
O
OH
branch point
O
O
OH
glucose
CH 2
CH 2OH
O
O
H
reducing end
OH
OH
OH
O
O
OH
OH
glucose
glucose
Cellulose is an interesting polymer. It is a homopolymer of glucose like starch except the linkages
joining the glucose units are :14 rather than :14. With this linkage flatter chains result which
layer on top of each other in a staggered fashion with interchain H-bonding, giving the cellulose its
strength. Cellulose is resistant to degradation by most acids and amylases and cannot be digested by
most animals. Cellulases are produced by certain bacteria and these bacteria live in the gut of grass
eating animals and termites. Other polysaccharides of biological interest are chitins (made up of
repeating N-acetyl glucosamines (NAGs) in a similar conformation to cellulose) which make up
crustacean exoskeletons, agarose (a galalctose polymer) and heparin.
CH2OH
CH2OH
O
O
O
OH
OH
OH
glucose
OH
glucose
cellulose