CARBOHYDRATES

Carbohydrates
aldehyde or ketone compounds with multiple
hydroxyl groups
constructed of carbon (carbo-) plus hydrogen
and oxygen (-hydrate)
simplest carbohydrates = monosaccharides, or
simple sugars
Cn(H2O)n

make up most of the organic matter on Earth

Functions of carbohydrates
energy stores, fuels, and metabolic
intermediates
structural framework of RNA and DNA
structural elements in the cell walls of
bacteria and plants
linked to many proteins and lipids

 Starch consists of chains

of linked glucose
molecules.

These chains are broken

down into individual
glucose molecules
Glucose catabolism
used to generate ATP
and building blocks for
other molecules.

Sugars can be aldoses or ketoses

Aldoses (e.g., glucose) have an
aldehyde group at one end.
H

Ketoses (e.g., fructose) have a

keto group, usually at C2.

CH2OH

HO

OH

OH

OH

OH

OH

HO

CH2OH

CH2OH

D-glucose

D-fructose

Examples of triose sugars

D and L designation

D, L designations
are based on the
configuration
about the single
asymmetric C in
glyceraldehyde
The lower
representations
are Fischer
Projections

CHO

CHO
H

OH

HO

L-glyceraldehyde

CHO
H

OH

CH2OH

D-glyceraldehyde

CH2OH

CH2OH

D-glyceraldehyde

CHO
HO

CH2OH

L-glyceraldehyde

 Monosaccharides often represented by Fischer projections

Most commonly occurring sugars are in the D conformation

For sugars with >1

chiral center, D or L
refers to the
asymmetric C
farthest from the
aldehyde or keto
group

No. of stereoisomers =
2n
where n = no. of
asymmetric Cs
e.g., 6-C aldoses have 4
asymmetric centers
16 stereoisomers (8
D-sugars and 8 Lsugars)

C
H C OH
HO C H
H C OH
H C OH
CH2OH
D-glucose

C
HO C H
H C OH
HO C H
HO C H
CH2OH
L-glucose

D - aldoses
containing
3, 4 and 5
carbon
atoms

6 carbon aldoses

D - Ketoses
containing
3, 4, 5 and 6
carbon
atoms

Isomeric sugars
Diastereomers - isomers that are not mirror images
of each other
have multiple asymmetric carbons

Epimers - sugars that differ in a single chiral center;

e.g.,
Galactose and glucose (C-4 epimers)
Glucose and mannose (C-2 epimers)

Epimerization of sugars
CHOH

CHO

OH

H
HO

C
HO

CHO

OH
H

HO

HO

OH

OH

OH

OH

OH

OH

CH2OH

CH2OH

D-Glucose

Enediol

CH2OH

D-Mannose

This equilibration can be catalyzed by hydroxide ion.

Pentoses and hexoses cyclize to form

furanose and pyranose rings
open-chain forms usually cyclize into rings
an aldehyde can react with an alcohol to form a
hemiacetal

Ketoses
a ketone can react with an alcohol to form a
hemiketal
C-2 keto group can react with C-6 OH group to form a
6-membered cyclic hemiketal or the C-5 OH group to
form a 5-membered cyclic hemiketal

 cyclic hemiacetal =six-membered

ring
called pyranose because of its
similarity to pyran

Cyclic hemiketal = 5-membered

Called furanose because of similarity
to furan

Pyranose formation

Two anomeric forms, designated and , can result because

of new chiral center at C1

6 CH2OH

6 CH2OH
5

H
4

OH

H
OH
3

H
2

H
1

OH

OH

a-D-glucose

OH

H
OH
3

OH

OH

b-D-glucose

Cyclization of glucose produces a new asymmetric center

at C1

2 stereoisomers are called anomers: a and b

Haworth projections represent the cyclic sugars as having

essentially planar rings, with the OH at the anomeric C1:
a (OH below the ring)
b (OH above the ring).

 An equilibrium mixture of glucose contains

~1/3 anomer
2/3 anomer
<1% of the open-chain form

Glucose stored by plants (starch) and animals

(glycogen)
Also present in cellulose; provides structural integrity
to the cells

Most biologically important sugars are six-carbon

hexoses that are structurally related to D-glucose

 Haworth
projection an
oversimplificati
on because
pyranose ring
is not planar
Most stable
conformation
= chair
less steric
hindrance;
axial positions
are occupied
by H atoms

Furanose formation

open-chain form of fructose cyclizes to a 5-membered ring

when the C-5 OH group attacks the C-2 ketone to form an
intramolecular hemiketal
Two anomers are possible

Fructose forms either

1. a 6-member pyranose ring, by reaction of the C2 keto group
with the OH on C6, or
2. a 5-member furanose ring, by reaction of the C2 keto group
with the OH on C5.

Other common monosaccharides

Galactose - found in milk as part of the disaccharide lactose

Ribose - five carbon sugar contained in RNA and DNA

form furanose rings

Reactions of monosaccharides
Oxidation - provides E for organisms
Produces sugar acids
For hexoses:
1. Oxidation at C1 aldonic acid
Detected by Benedicts, Barfoeds or Seliwanoffs test

2. Oxidation at C6 uronic acid

3. Oxidation at C1 and C6 aldaric acid

Sugar acids
H

CHO

COOH

OH

HO

OH

HO

OH

HO

OH

OH

OH

OH

OH

OH

CH2OH

D-glucose

CH2OH

D-gluconic acid

COOH

D-glucuronic acid

aldehyde at C1, or OH at C6, is oxidized to a carboxylic

acid; e.g., gluconic acid, glucuronic acid.

Oxidation of sugars

Sugars that react are called reducing sugars; those that

do not are called nonreducing sugars

Reducing sugars
Reducing sugar a carbohydrate that is oxidized by
Tollens, Fehlings or Benedicts solution.
Tollens: Ag+ Ag (silver mirror)

Fehlings or Benedicts: Cu3+ (blue) Cu2+

(red ppt)
These are rxns of aldehydes and a-hydroxyketones.
All monosaccharides (both aldoses and ketoses) and
most disaccharides are reducing sugars.

Glycoside formation
Glycoside = non-reducing
sugar
C1 not free because
linked with R group
Usually, -OH group
bonded to anomeric C in
cyclic form
Modified sugar has
differences in reactivity
compared to the parent
monosaccharide
e.g., methyl -Dglucopyranoside =
nonreducing sugar

Hemiacetal + R OH full
acetal/glycoside

Reactivity of hydroxyl groups in

carbohydrates
Hydroxyl
groups in
carbohydrates
undergo
reactions
typical of
alcohols; e.g.,
Acylation
alkylation

HOCH2
HO
HO

OH

4CH3I

OCH3
Ag2O, CH3OH

CH3OCH2

CH3O
CH3O

CH3O

(97%)

OCH3

Alkylation of methyl a-D-glucopyranoside

Lactones
Produced from oxidation of aldose
e.g., -D-glucose lactone in presence of
silver-ammonia complex
basis of Tollens test
Positive result = silver mirror

Exhaustive methylation
R-OH reactions only affect anomeric Cs
Other R groups can be methylated using
dimethylsulfate
Used to determine presence of glycosidic linkages

Reduction of carbohydrates
Carbonyl group of open-chain form is reduced
to an alcohol
C=O

C OH

Product is called an alditol.

lacks a carbonyl group, so cannot cyclize to a
hemiacetal.
e.g., sorbose sorbitol
Xylose xylitol

Reduction of D-Galactose
reducing agent: NaBH4, H2O
(catalytic hydrogenation can also be used)
CH
a-D-galactofuranose
b-D-galactofuranose
a-D-galactopyranose

b-D-galactopyranose

CH2OH

O
OH

OH

HO

HO

HO

HO

OH
CH2OH

OH
CH2OH

D-Galactitol (90%)

Reduction reactions
Formation of sugar alcohols
C OH to C H
e.g., -D-ribose -Ddeoxyribose

Esterification reactions
-OH groups of sugars behave exactly like all
other alcohols
May reach with acids, acid derivatives,
phosphates, etc
e.g., phosphates esterified to ribose or
deoxyribose

Modified monosaccharides

Carbohydrates can be modified by the addition of substituents

other than hydroxyl groups.
Such modified carbohydrates are often expressed on cell
surfaces.

Sugar derivatives
CH2OH

CH2OH
O

H
H
OH

H
OH

H
OH

OH
H

NH2

H
O OH

OH
H

CH3

a-D-glucosamine

a-D-N-acetylglucosamine

amino sugar - an amino group substitutes for a hydroxyl.

e.g., glucosamine
The amino group may be acetylated
e.g., N-acetylglucosamine

O
H3C

NH
R
H

COO

R=
OH

HC

OH

HC

OH

CH2OH
OH

N-acetylneuraminate (sialic acid)

N-acetylneuraminate (also called sialic acid) is often

found as a terminal residue of oligosaccharide chains
of glycoproteins.
imparts negative charge to glycoproteins
COOH group tends to dissociate a proton at
physiological pH

Formation of sugar sulfates

Sulfates esterified at C-2, C-4 or C-6 of aldoses
Found mostly in proteoglycans of ECM
Presence of sulfate groups mean that sugar is
negatively charged at physiological pH

The major glycosaminoglycans

Polysaccharides

Polysaccharides
play vital roles in energy storage, and in maintaining
structural integrity of an organism
May be
1. Homopolysaccharides
all of the monosaccharides are the same
e.g., starch, glycogen

2. Heteropolysaccharides
>1 type of monosaccharide
Usually just 2 alternating monosaccharide units

Complex carbohydrates formed by linkage

of monosaccharides
Oligosaccharides formed by O-glycosidic linkages
between monosaccharide units
Since monosaccharides have multiple OH groups,
various glycosidic linkages are possible

Glycosidic bonds
A large no. of different
glycosidic bonds can be formed
between 2 sugar residues
For example, glucose could be
bonded to fructose by any of
the following linkages:

o (11)
o (12)
o (13)
o (14)
o (16)
o (11)
o (12)
o (13)
o (14)
o (16)

Common disaccharides

Common disaccharides

Starch
nutritional reservoir in plants; makes up >50% of
carbohydrates ingested by humans
2 forms: amylose and amylopectin

1. Amylose
unbranched
consists of glucose residues in -1,4 linkage.

2. Amylopectin
branched form, but less dense compared to
glycogen
Has -1,6 linkage per 30 -1,4 linkages

Both forms rapidly hydrolyzed by -amylase

Glycogen
Storage form of
glucose in animals
Main chain: glucose
linked by -1,4glycosidic bonds
Branches: formed by 1,6-glycosidic bonds

Cross section of a
glycogen molecule

Branch point in glycogen

2 chains of glucose molecules joined by -1,4-glycosidic bonds

are linked by an -1,6-glycosidic bond to create a branch point
-1,6-glycosidic bond forms every 10 glucose units

Cellulose
the other major polysaccharide of glucose in plants
one of the most abundant organic compounds in the
biosphere
unbranched polymer of glucose residues joined by 1,4 linkages
serves a structural rather than a nutritional role
Mammals lack cellulases; cannot digest wood, vegetable
fibers

Glycosidic bonds determine polysaccharide structure

-1,4 linkages favor straight chains, which are optimal for

structural purposes
-1,4 linkages favor bent structures, which are more suitable
for storage.

Chitin
long-chain polymer of a N-acetylglucosamine
main component of the exoskeletons of arthropods, such as
crustaceans and insects

Dextran
synthesized from sucrose
by certain lactic-acid
bacteria
e.g., Leuconostoc
mesenteroides,
Streptococcus mutans

Found in dental plaque

Similar to amylopectin
main chains formed by
(16) glycosidic linkages
side branches attached by
(13) or (14) linkages

Dextran: uses
used in eye drops as a lubricant
used to replace lost blood
when replacement blood is not
available
BUT must be used with caution;
does not contain electrolytes

Present in certain IV fluids to

1. solubilise other factors, e.g.,
iron (=iron dextran).
2. Provide energy: digested into
glucose and free water

Peptidoglycan
Makes up bacterial cell walls
linear polysaccharide chains
cross-linked by short peptides
mechanical support
prevents bacteria from
bursting in response to their
high internal osmotic pressure
Penicillin inhibits cross-linking
transpeptidase

Formation of crosslinks in peptidoglycan

catalyzed by glycopeptide transpeptidase
Penicillin mimics d-Ala-d-Ala moiety of normal substrate
Bound penicillin forms covalent bond with Ser at active site
of enzyme
penicilloyl-enzyme does not react further

Glycoproteins
proteins that contain oligosaccharide chains
covalently attached to their polypeptide sidechains
sugars may be attached to
1. N in asparagine side chain (N-linkage)
2. O in the side chain of serine or threonine (Olinkage)

Glycosidic bonds between proteins and carbohydrates

Blood group antigens

Carbohydrates attached to glycoproteins,
glycolipids on the surfaces of RBCs
Antigenic determinants

If an antigen not normally present in a person

is introduced, the person's immune system
recognizes it as foreign

Blood group antigens

Influenza virus binds to sialic acid

residues
ability of viruses to infect
specific cell types due to their
interaction with particular
structures or receptors on the
cell surface
In some cases, receptors are
carbohydrates
e.g., influenza virus recognizes
sialic acid residues present on
cell-surface glycoproteins called
hemagglutinin

Structure of a part of
influenza hemagglutinin

Glycosaminoglycans
have disaccharide repeating units containing a
derivative of an amino sugar
either glucosamine or galactosamine

At least one of the sugars in the repeating unit has a

negatively charged carboxylate or sulfate group
usually attached to proteins to form proteoglycans

The major glycosaminoglycans

Proteoglycans
Almost all GAGs covalently attached to protein in the
form of proteoglycans
Found in animal cells
distinguished from other glycoproteins by the nature,
quantity, and arrangement of their sugar side chains
GAGs, proteoglycans can associate to form huge
polymeric complexes in the ECM
GAG chains can form gels of varying pore size, charge
density

The linkage between a GAG chain and its core protein in a

proteoglycan molecule

Proteoglycan functions
1. may serve as selective sieves to regulate the traffic
of molecules and cells according to their size,
charge, or both
2. associates with fibrous matrix proteins, e.g.,
collagen
3. function as lubricants and structural components
in connective tissue
4. Mediate adhesion of cells to the extracellular
matrix
5. bind factors that stimulate cell proliferation

 Aggrecan
major component of cartilage
MW ~ 3 106 daltons with over 100 GAG chains

Decorin
secreted by fibroblasts
has a single GAG chain

Glycoproteins vs proteoglycans
1. Glycoproteins
contain 160% carbohydrate by weight
numerous relatively short, branched oligosaccharide
chains

2. Proteoglycans
can contain as much as 95% carbohydrate by weight
Most carbs = long, unbranched GAG chains, each
typically ~ 80 sugars long