Unit-4

4. Chemistry Carbohydrates
 Introduction

Definition and Biological Roles of carbohydrates

♣  Formerly carbohydrates were considered to be hydrates of carbon with the
empirical formula CnH2nOn /(CH2O)n.
♣ But later this definition found to have short comings b/se; on one hand
some carbohydrates for example rhamnose (C6H12O5) do not comply with
this definition and empirical formula.
♣ On the other hand the definition includes some non carbohydrate
compounds like lactic acid (C3H6O3), empirical formula CH2O.
♣ Therefore carbohydrates are, more precisely, defined as polyhydroxy
aldehydes or ketones or their derivatives.
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 Example: glucose and fructose
contain many (poly) hydroxyl
(OH) groups except at C-1 in
glucose, and C-2 in fructose.
 Glucose contain aldehyde
functional group at C-1 and
fructose contain keto group at
C-2.

Carbohydrates

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 Biological Roles of Carbohydrates

1) Carbohydrates are the primary product of plant

photosynthesis and hence the major source of energy for
living organisms.
2) Serve as the metabolic precursors (carbon sources) of all
other biomolecules.
3) Structural carbohydrates, like cellulose serve as component
of cell wall of plants; and chitin as component of
exoskeleton of arthropods and has a protective role.
4) Ribose sugars serve as a constituent of nucleotides.
 Nucleotides are basic units of nucleic acids (DNA & RNA)

and coenzymes like NADH & FADH2 and ATP which is a

purine base nucleotide.

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5) Carbohydrates are present in the cell membrane as protein-
carbohydrate complexes (glycoproteins) and lipid-carbohydrate
complexes (glycolipids).
 The glycolipids and glycoproteins are found on the outer leaflet of
the lipid bilayer of membranes and are referred to as glycocalyx.
 Glycocalyx mediates the cell-cell interaction and recognition.

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6) Glucose is the most versatile (multi-potent) carbohydrate. It is
stored as starch (the primary product of photosynthesis in
plants) and as glycogen in animals.

◦ After digestion, carbohydrates are mainly absorbed in to the blood

stream in the form of glucose.

◦ All carbohydrates either dietary or indigenous can be converted to

glucose.
Therefore metabolic pathways of other carbohydrates finally converge to
metabolism of glucose.

◦ Glucose also gives rise to all other carbohydrates with specific function
like the ribose sugars in nucleic acids.

◦ Glucose is the immediate source of energy for many mammalian tissues.

Cells such as brain cells and RBC can utilize only glucose as a source of
energy
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Classification

 According to the number of sugar units and the size of the

molecule there are three major classes of carbohydrates:

1) Monosaccharides  Carbohydrates that have a single (mono)

polyhydroxy aldehyde or ketone unit and hence cannot be hydrolysed into
simpler carbohydrates.
 Ex: glucose, fructose, ribose.

2) Oligosaccharides  Formed of 2-10 monosaccharide units.

 Ex:maltotriose (a trisaccharide). Oligosaccharides often exist as conjugates

of lipids or proteins.

 oligosaccharides that contain two monosaccharide units are known as

disaccharides. Disaccharides are the most abundant oligosaccharides in
cells and occur in free form.

3) Polysaccharides  Formed of more than 10 monosaccharide units

Ex: starch, glycogen, cellulose.
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 Monosaccharides

 Classification
 Structure
 Properties
 Optical activity
 Isomerism
 Reducing property

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 Monosaccharides
Classification:

 Classified according to:

1) Functional groups as ALDOSES
& KETOSES

 Aldoses contain
aldehyde at C-1 Ex:
glucose
 Ketoses contain
keto group at C-2 Ex:
fructose

2) The number of carbons they contain

as
 trioses,
 tetroses,
 pentoses etc.
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 The major monosaccharides contain three to seven carbon atoms
(aldohexoses and ketohexoses are the most common)

Aldoses Ketoses

Triose (3C) glycerose dihydroxyacetone

Tetrose (4C) erythrose erythrulose

Pentose (5C) ribose ribulose

Hexose (6C) glucose fructose

Heptose (7C) sedoheptulose

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Structure:

Monosaccharides are represented in 3 ways

1) Fischer’s convention formula (Straight

chain formula) that shows D & L
isomers (enantiomers)

2) Haworth’s perspective formula

(Cyclic/ring structures) that shows the -
and - configueration (anomers) in
water solution/in cells

3) Boat and chair conformations.

The chair conformation is the

stable and most common one
because of less steric hindrance.

Note that; Configuerations interconvert by

breaking a bond but conformations does
not involve bond breakage.
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Cyclic structures of monosacharides
Straight chain structural formula accounts for only some properties.

In aqueous solutions such as in cells, aldotetroses and all monosaccharides

with five or more carbon atoms occur predominantly as cyclic (ring)
structures called the Haworth perspective formula.

The formation of these ring structures is the result of a general

intramolecular reaction between:
 the carbonyl group (the aldehyde in aldoses or the ketone in ketoses)

and
 the oxygen of a hydroxyl group (alcohol) along the carbon chain. This

cyclization leads to the formation of:

◦ Sugars with 6 membered rings known as pyranoses and with 5

membered rings known as furanose. They resemble the pyran and
furan rings respectively:

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 In general in aldoses for
example in aldohexoses like
in D-glucose hemiacetals
are formed by the reaction
between the free hydroxyl
group at carbon 5 and the
aldehyde carbon (carbon 1).

 In D-glucose the cyclization

forms new chiral centers by
making the aldehyde carbon
asymmetric (anomeric
carbon) and produce two
stereoisomers, designated
as -D-glucopyranose (OH
down) and -D-
glucopyranose (OH up).
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Glucose can also exist in
five membered ring
(pyranose form)
formed b/n C-1 and
C-4 OH.
However the pyranose
form is more stable.

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 Ketoses can also exist in
cyclic forms. In ketohexoses
for example in D-fructose,
the free hydroxyl group at
carbon 5 reacts with the
ketone group at carbon 2
forming a furanose ring by
a hemiketal linkage.

 This will produce two

stereoisomers, designated
as -D-fructofuranose and
-D-fructofuranose because
carbon number two has
become anomeric carbon as
in glucose (C-1).

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Fructose exist also in five
membered ring (pyranose)
form formed b/n C-2 and
C-6 OH.

However The more common

anomer of D-Fructose is -
D-fructofuranose.

In the Haworth perspective

formulas, the ring hydroxyl
group points down in the -
anomeric form but points
up in the -anomer

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Properties:
i) Optical property (chirality):
 Chirality is a property of molecules that contain a
chiral (asymmetric carbon atom).
 A chiral carbon is a tetrahedral carbon atom with

4 distinct substituent.
 Chirality describes the handedness of a molecule

that is observable by the ability of a molecule to

rotate the plane of polarized light
 either to the right (by a positive angle) hence it is

called Dextrorotatory (designated as d or +) or

 to the left (by a negative angle) hence it is called

Levorotatory designated as l or -.

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 ii) isomerism:

 Isomers: compounds that have same chemical formula but, different structural
formula.
 Ex: glucose, fructose, mannose, galactose are all–C6H12O6 but differ in structural
formula.
 There are different types of isomerisms but stereoisomerism is particularly
importannt in biological interconversions:

Stereo isomerism:
Is a property of chiral molecules that occur due to difference in the configueration or
position of chemical groups such as H, OH and NH3+ around the chiral center.

There are different types of stereoisomers such as:

 Enantiomers (D- and L-isomers)

 Epimers
 Anomers (- and -cyclic forms)

 Geometric isomers (cis-trans isomers)

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a) Enantiomerism (D and L isomerism):

 involves
the designation of chiral molecules as D and L
isomers using D and L glyceraldehydes as a reference.

 Glyceraldehydeis called the reference sugar, because it

contains only one asymmetric (sub-terminal) carbon atom.

 InD glyceraldehyde the OH group on the chiral carbon is

to the right but it is to the left in L glyceraldehyde.

 The D and L isomers are mirror images of one another and

are called as enantiomers.
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Ex: D and L glucose
Enantiomers differ in the
configuration of their
hydroxyl groups around all
their chiral carbons.

Therefore to designate
monosaccharides with more
than one chiral center such
as glucose, the chiral carbon
most distant from the
carbonyl carbon (subterminal
or penultimate) carbon is
used as a reference.

 Note: most naturally occurring

monosaccharides are the D-forms
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b) Epimers:
 Two D-sugars or two L-

sugars that differ in the

configuration around
only one of their chiral
carbon are called
epimers.
 Example: D-glucose and

D-mannose, which differ

only in the position of
OH at C-2, are epimers,
as are D-glucose and D-
galactose (which differ
at C-4).
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c) Anomers:
 Are the - and - cyclic forms formed arround the anomeric

carbon
Mutarotation: Is the interconversion of the - and - anomers
of monosaccharides in aqueous solution through the
formation of the open chain form.
 Thus in aqueous solution of either the - or the -

configuration, the specific rotation angle changes and

eventually forms identical equilibrium mixtures with a
specific rotation angle known for the sugar.
 For example freshly prepared -glucose has a specific

rotation of +112o that decreases gradually till it stabilizes at

+52.5 o.
 Similarly, freshly prepared -glucose has a specific rotation of

+19 o that gradually increases till getting stabilized at +52.5 o

(the specific rotation for glucose).

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Therefore due to
mutarotation an aqueous
solution of glucose consists
of
 about 36% -D-glucose;

 63% -D-glucose;

 < 0.1% open chain form (the

reactive form) and

 very small amounts of the

- and -glucofuranoses
also called γ-glucose forms.

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iii) Reducing property

 Monosaccharides with free

anomeric carbon can reduce
oxidizing agents such as ferric
(Fe3+) or cupric (Cu2+) ions to
their ferrous (Fe2+) or cuprous
(Cu1+) forms rspectively.

 But the sugars aldehyde or

ketone group is oxidized to a
carboxyl group by the ferric or
cupric ions.

 Hence the sugars act as a

reducing agents. This is
called reducing property of
sugars.

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 This reducing property of sugars is the basis of
Fehling’s and Benedict’s reaction which are
qualitative tests for reducing sugars.

 Both Fehling’s and Benedict’s reagents contain

cupric ion as the active substance and if these
reagents are made to react with a reducing
sugar solution the sugar will reduce the cupric
ion converting it to cuprous oxide (Cu2O) in
which copper has +1 oxidation state hence it is
reduced.

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 The redox reaction
forms a red precipitation
of Cu2O which is a
positive test for the
presence of a reducing
sugar.
 There is a spectrum of
color changes as the
concentration of the
reducing sugar
increases
 Note: the original color
of Benedict’s solution is
blue
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 Fehling’s and Benedict’s reaction has been used to measure
elevated glucose levels in blood and urine in the diagnosis of
diabetes mellitus by measuring the amount of oxidizing agent
reduced by a solution of a sugar.
 But this test gives a positive result for other reducing sugars (not
specific for glucose) too.
 Therefore now a more sensitive method for measuring blood
glucose that employ an enzyme, glucose oxidase is used.
 Blood glucose concentration is determined by measuring the
amount of H2O2 produced.

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 Disaccharides
 Are carbohydrates formed of two monosaccharides
joined together by O-glycosidic linkage.

 This linkage is formed when a hydroxyl group of one

sugar reacts with the anomeric carbon-OH of the
other (the glycosyl residue) with a release of water
molecule.

 The linkage can be - or β- depending upon the

type of the anomeric carbon participating in the
linkage.

 Disaccharides can be hydrolyzed to yield their free

monosaccharide components.
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Disaccharides can be Reducing or Non reducing:

 Reducing disaccharides: disaccharides in which the anomeric

carbon of one of the component monosaccharides is not
involved in the glycosidic linkage.

  have free anomeric carbon (reducing end) and can take the
linear (open chain) form that react with an oxidizing agent and
reduce it.
 Eg. Maltose, lactose, isomaltose, cellobiose

 Non-reducing disaccharides: the anomeric carbon of both the

component monosaccharide(s) is involved in the glycosidic
bond (form non reducing ends).

  don’t have free anomeric carbon, they cannot take the

linear form and therefore have no reducing property. Eg.
Sucrose, trehalose.
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Reducing Disaccharides:

1. Maltose (malt sugar)

 Formed of two glucose

units linked by α (1→4)
linkage.
 Not common in nature
except in germinating
seeds.

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2. Isomaltose

 Formed of two glucose

units linked by  (1→6) CH2OH

linkage. H
O
H
H
 The anomeric carbon OH H
1

of the second glucose OH

O

can be in  or  H
-Glucose
OH
6CH2
anomeric form. O
H OH ..... H
H
OH H
OH H ..... OH

H OH
Glucose
and isomaltose

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3. Lactose (milk sugar):

 Formed of -galactose
and a glucose units
linked by  (1→4)
linkage.
 Glucose can be in - or
- anomeric forms.

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4. Cellobiose

 Formed of of two
glucose units linked by CH2OH CH2OH
O
 (1→4) linkage. O
H OH
H
 It is produced from H
1 O 4 H
OH H
partial hydrolysis of OH
OH H
H H

cellulose. H OH
H OH
 It is indigestible. -Glucose -Glucose
Cellobiose

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Non reducing Disaccharides:

1. Sucrose (cane/beat) sugar

 Formed of -glucose linked to

-fructose by -1↔  -2
linkage.

 Sucrose is formed by plants but

not by animals.

 It is a major intermediate
product of photosynthesis.

 In animals dietary sucrose is

absorbed after hydrolysis by
the enzyme sucrase.

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2. Trehalose

 Formed of 2 -glucose
units linked by  (1→1)
linkage.
 Present in a highly
toxic lipid extract from
Mycobacterium
tuberculosis

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 Polysaccharides
 Are high molecular weight carbohydrates formed of
more than 10 monosaccharide units.
 Classified based on type of Monosaccharide units as

 Homopolysaccharides and Heteropolysacharides

i) Homopolysaccharides –made of single type of residue

 Eg: Starch and glycogen–made of only glucose residues,
 Inulin– made of only fructose residues.
 Based on function homopolysaccharides are classified as
◦ Structural such as cellulose, chitin
◦ Storage such as starch, glycogen
ii) Heteropolysaccharides –composed of more than one type of sugar
units. Eg. Glycose Aminoglycans (GAGs). Ex. Hyluronic acid,
dermatan sulphate, keratan sulphate, heparin and heparansulphate.
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Starch
is a homopolymer of glucose. It is the most abundant dietary
carbohydrate present in different parts of the plant as starch granule.
The granules contain its two forms (Amylose and Amylopectin)

Aylose Amylopectin
Form the core of the granule and Form the outer shell and comprises
comprises of (15-20%) of (80-85%).
Branched form of starch
Nonbranching helical structure
branched chains formed at intervals
Glucose units are linked by 1→4
of 24 -30 residues by 1→6
linkages
linkages and main chain 1→4
One reducing end and one non linkages
reducing end. Contains many non reducing ends
Water soluble and it but only one reducing end
Gives blue color with iodine solution Water insoluble in and gives red
color with iodine solution.
Amylose
Amylopectin
Starch granule

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 CH2OH CH2OH

O O
H H H
H H
H
4 1 4 1
OH H OH
O
O O

H OH H OH n
Amylose

CH 2OH CH2OH

O O
H H H
H H
H
4 1 4 1
OH H OH
O O
O
H OH H OH

CH CH2OH
CH2OH CH2OH 62 O
O O H
O H H H H
H H H H
H H
H
1 4 1 4 1
4
OH H 1 4 OH OH H OH
O
O O
O O
H OH
H OH H OH H OH n
Amylopectin

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 Glycogen
 Branched homopolymer of glucose made of α(1→4) glucose units
in the main chain with α(1→6) linked branch points like
amylopectin.
 But branching points are located at intervals of 8 -12 glucose

residues hence is more highly branched more compact and shorter

than amylopectin.
 Glycogen is water-soluble and gives red color with iodine solution.

 It is storage polysaccharide of animals.

 In mammals it is primarily stored in liver and skeletal muscle but

more abundant in liver where it may constitute 7% of the wet

weight.
 found as large granules composed of highly branched glycogen

molecules built up on a crystalline protein known as glycogenin.

 Granules also contain the enzymes responsible for glycogen

metabolism. 39
 Glycogen is synthesized from the surplus glucose after meal.
 The pathway of glycogen synthesis is termed as

glycogenesis.
 The enzymes involved in glycogen synthesis are:

 glycogen synthase that catalyzes the formation of the  1→4

glycosidic linkages of the linear chain and

 the branching enzymes that catalyze the formation of the -

1→6 branch points.

 The pathway of glycogen degradation is known as

glycogenolysis. It occurs during early starvation period or

between meals.
 The enzymes that catalyze glycogenolysis are glycogen

phosphorylase that cleaves the -1→4 linkages of the linear

chain and the debranching enzymes that cleaves the -1→6
branching points.
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 Glycogen has one reducing end and many non reducing
ends like amylopectin.

 But has much more non reducing ends than

amylopectin due to its extensive branching.

 This makes glycogen more water soluble than

amylopectin hence easily dissolved in liver and muscle.

 Moreover degradative enzymes that act only at non

reducing ends can work simultaneously on the many
branches hence the branching facilitate metabolism.

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 Cellulose

 Unbranched structural homopolymer of glucose composed of

-glucose units linked by -1,4-glycosidic linkage.

 It is the major structural polysaccharide in nature and it is

found in the cell walls of plants;

 It is a fibrous, tough, water-insoluble polysaccharide results

in formation of long fibers of plant structure (Eg cotton fibers)
and paper.

 It is the most abundant polysaccharide.

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Summary Cellulose vs Glycogen and Starch

Cellulose Starcg & Glycogen

 Structurral
 Storage
 -glucose units linked by -
 -glucose units and -
1,4-glycosidic linkage
 Not hydrolyzed by salivary and 1,4 linkages
pancreatic -amylases in the  hydrolyzed by salivary
intestine and pancreatic -
 most animals lack enzyme to
amylases in the
hydrolyze the β1→4 linkages
and intestine
 cannot use cellulose as a fuel  Are fuel sources for
source. many animals
 Digested only by ruminant

animals
(that harbor microbes that
secret cellulase in their rumen.
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Chitin:

 It is linear composed of -
N-acetylglucosamine
residues in -1,4-linkage.
CH2OH CH2OH
  O O
H H
 Differs from cellulose only in H H
O 4 OH 1 O O
the replacement of the OH at H 4
OH H 1
H H
C-2 of glucose with an
acetylated amino group. H NH-CO-CH3 H NH-CO-CH3 n
 Like cellulose it forms -N-acetyl-glucosamine -N-acetyl-glucosamine
extended fibers and not Chitin
digested by vertebrates.

 It is principal component of
exoskeletons of arthropods
(insects). It is second most
abundant polysaccharide.
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 Heteropolysaccharides:

Glycosaminoglycans (GAGs):
 Are also known as mucopolysaccharides

 Long unbranched polysaccharides containing a repeating disaccharide unit.

 GAGs are generally important as:

i) components of extracellular matrix (ECM) also called ground

substance and
ECM is a gel-like material found in the extracellular space in the
tissues of multicellular animals.
ii) as a component of connective tissues like skin, bone cartilage
etc.
Other GAGs of physiological significance are:
◦ Hayaluronic acid
◦ Heparin
◦ Heparan sulfate
◦ Dermatan sulfate
◦ Chondroitin sulfate
◦ Keratan sulfate
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