Biomolecules: Carbohydrates

Importance of Carbohydrates
❑ Distributed widely in nature

❑ Key intermediates of metabolism (sugars)

❑ Structural components of plants (cellulose)

❑ Storage form in plants (starch) and animals (glycogen)

❑ Estimated that more than 50% of the dry weight of the earth's
biomass—all plants and animals—consists of glucose polymers

❑ Central materials of industrial products: paper, lumber, fibers

❑ Key component of food sources: sugars, flour, vegetable fiber

❑ Contain OH groups on most carbons in linear chains or in rings

 Chemical Formula and Name
❑ Carbohydrates have roughly as many O’s as C’s (highly oxidized)

❑ Since H’s are about connected to each H and O the empirical

formulas are roughly (C(H2O))n

❑ Appears to be “carbon hydrate” from formula

❑ Current terminology: natural materials that contain many hydroxyls

and other oxygen-containing groups
 hydrate of carbon, C6(H20)6

Carbohydrate is used to refer loosely to the

broad class of polyhydroxylated aldehydes
and ketones commonly called sugars
 Sources
❑Glucose is produced in plants through
photosynthesis from CO2 and H2O

❑Glucose is converted in plants to other small

sugars and polymers (cellulose, starch)

❑Dietary carbohydrates provide the major source

of energy required by organisms
 Classification of Carbohydrates
❑ Simple sugars (monosaccharides) can't be converted into
smaller sugars by hydrolysis.

❑ Carbohydrates are made of two or more simple sugars

connected as acetals (aldehyde and alcohol) or ketals (ketone
and alcohol) and can be disaccharides, oligosaccharides and
polysaccharides

❑ Sucrose (table sugar): disaccharide from two

monosaccharides (glucose linked to fructose),

❑ Cellulose is a polysaccharide of several thousand glucose

units connected by acetal linkages (aldehyde and alcohol) or
glycosidic bonds.
 Aldoses and Ketoses
❑ aldo- and keto- prefixes identify the nature of the carbonyl
group

❑ -ose suffix designates a carbohydrate

❑ Number of C’s in the monosaccharide indicated by root (-tri-,

tetr-, pent-, hex-)
 Depicting Carbohydrate Stereochemistry:
Fischer Projections
❑ Carbohydrates have multiple chirality centers and common sets of
atoms
❑ A chirality center C is projected into the plane of the paper and other
groups are horizontal or vertical lines
❑ Groups forward from paper are always in horizontal line. The oxidized
end of the molecule is always higher on the page (“up”)
❑ The “projection” can be seen with molecular models
❑A tetrahedral carbon atom is represented in a Fischer projection by two
crossed lines
❑The horizontal lines represent bonds coming out of the page, and the
vertical lines represent bonds going into the page
 Depicting Carbohydrate Stereochemistry:
Fischer Projections
❑ A given chiral molecule can be drawn in many different ways
❑ Often necessary to compare two projections to see if they
represent the same or different enantiomers
❑ Fischer projections can be moved around on the paper, but only
two kinds of motions are allowed
❑ Moving a Fischer projection in any other way inverts its meaning
❑ A Fischer projection can be rotated on the page by 180°, but not by
90° or 270°.
❑ Only a 180° rotation maintains the Fischer convention by keeping the
same substituent groups going into and coming out of the plane
 Fischer Projections
❑A 90° rotation breaks the Fischer convention by
exchanging the groups that go into the plane and those
that come out

❑The —H and —OH groups come out of the plane before

rotation but go into the plane after a 90° rotation
 Fischer Projections
❑A Fischer projection can have one group held steady
while the other three rotate in either a clockwise or a
counterclockwise direction

❑The effect is simply to rotate around a single bond, which

does not change the stereochemistry
R,S stereochemical designations
• Assign priorities to the four substituents on the chiral carbon
• Place the group of lowest priority, usually H, at the top of the
Fischer projection by using one of the allowed motions.
– The priorities of the groups are (1) -NH2, (2) -C02H, (3) –CH3
and (4) -H
– To bring the group of lowest priority (—H) to the top, we might
want to hold the —CH3 group steady while rotating the other
three groups counterclockwise
R,S stereochemical designations

❑Going from first- to second- to third-highest

priority requires a counterclockwise turn,
corresponding to S stereochemistry.
 Stereochemical Reference
❑ The reference compounds are the two enantiomers of glyceraldehyde,
C 3 H 6 O3

❑ A compound is “D” if the hydroxyl group at the chirality center farthest

from the oxidized end of the sugar is on the right or “L” if it is on the left.

❑ D-glyceraldehyde is (R)-2,3-dihydroxypropanal

❑ L-glyceraldehyde is (S)-2,3-dihydroxypropanal
 Rosanoff Structural Families
❑ The structures show how the “D” and “L” family members
are identified by projection of the bottom chirality center

❑ The rest of the structure is designated in the name of the

compound

❑ The convention is still widely used

 The D-Sugar Family
• Correlation is always with D-(+)-glyceraldehyde
 D, L Sugars
❑ Glyceraldehyde exists as two enantiomers, first identified by
their opposite rotation of plane polarized light

❑ Naturally occurring glyceraldehyde rotates plane-polarized

light in a clockwise direction, denoted (+) and is designated
“(+)-glyceraldehyde”

❑ The enantiomer gives the opposite rotation and has a (-) or “l”
(levorotatory) prefix

❑ The direction of rotation of light does not correlate to any

structural feature
"RIBs ARe eXtra Lean”
"All altruists gladly make gum in gallon tanks
Cyclic Structures of Monosaccharides: Hemiacetal Formation

• Alcohols add reversibly to aldehydes and ketones, forming

hemiacetals or hemiketals
Hemiacetal/Hemiketal and acetal/ketal Formation
 Internal Hemiacetals of Sugars
❑ Intramolecular nucleophilic addition creates cyclic hemiacetals in
aldose

❑ Five- and six-membered cyclic hemiacetals are particularly stable

❑ Five-membered rings are furanoses. Six-membered are pyranoses

❑ Formation of the cyclic hemiacetal creates an additional chirality

center giving two diasteromeric forms, designated  and b

❑ These diastereomers are called anomers

❑ The designation  indicates that the OH at the anomeric center is

on the same side of the Fischer projection structure as hydroxyl
that designates whether the structure is D or L
Diastereomers= differ only in the configuration of C1
Anomers

In carbohydrate chemistry diastereomers

differing only at the hemiacetal or acetal carbon
are called anomers, and the hemiacetal or
acetal carbon atom is called the anomeric
carbon atom.
Fischer Projection Structures of Anomers:
Allopyranose from Allose
 Drawing Chair Conformations
❑ Pyranose rings are not flat and can assume several different
conformations
❑ The most stable conformation is the "chair" conformation
❑in which the bulky atomic groups (e.g., -OH and -CH2OH)
are equatorial or within the plane of the ring
❑ The hydrogens would then be axial or perpendicular to the
plane of the ring
❑ Only in β -D-glucopyranose are all of the bulky groups equatorial;
thus, β -D-glucopyranose is more stable than α -D-glucopyranose,
in which the C-1 hydroxyl group is axial to the ring
Monosaccharide Anomers: Mutarotation

❑ The two anomers of D-glucopyranose can be crystallized

and purified

❑-D-glucopyranose melts at 146° and its specific

rotation, []D = 112.2°;

❑b-D-glucopyranose melts at 148–155°C a specific

rotation of []D = 18.7°

❑ Rotation of solutions of either pure anomer slowly change

due to slow conversion of the pure anomers into a 37:63
equilibrium mixture ot :b called mutarotation
 Mechanism of Mutarotation Glucose

❑ Occurs by reversible ring-opening of each anomer to the open-chain

aldehyde, followed by reclosure

❑ Catalyzed by both acid and base

 Reactions of Monosaccharides
❑ Ester and Ether Formation

❑ ⎯OH groups can be converted into esters and ethers, which are often
easier to work with than the free sugars and are soluble in organic
solvents.
❑ Esterification by treating with an acid chloride or acid anhydride in the
presence of a base

❑ All ⎯OH groups react

 Williamson ether synthesis
• Carbohydrates are converted into ethers by treatment with an
alkyl halide in the presence of base

• Mild base instead of a strong base is required

• α-D-glucopyranose is converted into its pentamethyl ether in

85% yield on reaction with iodomethane and Ag20.
 Glycoside Formation
• The treatment of a hemiacetal with an alcohol and an acid
catalyst yields an acetal.

• Treatment of a monosaccharide hemiacetal with an alcohol

and an acid catalyst yields an acetal called a glycoside
 Biological Ester Formation: Phosphorylation
❑ Carbohydrates occur not only in the free form but also linked
through their anomeric center to other molecules such as lipids
(glyco-lipids) or proteins (glycoproteins)

❑ Glycoconjugates

❑components of cell walls and are crucial to the mechanism

by which different cell types recognize one another

❑ Glycoconjugate formation occurs by reaction of the lipid or

protein with a glycosyl nucleoside diphosphate

❑ The purpose of the phosphorylation is to activate the anomeric

—OH group of the sugar and make it a better leaving group
Biological Ester Formation: Phosphorylation
 Reduction of Monosaccharides
❑ Treatment of an aldose or ketose with NaBH4 reduces it to a
polyalcohol called an alditol
❑ Only a small amount of the open-chain form is present at any given
time
❑ D-Glucitol is itself a naturally occurring substance present in many
fruits and berries
❑ D-sorbitol, as a sweetener and sugar substitute in foods.
 Oxidation of Monosaccharides
• An aldose is easily oxidized to yield the corresponding carboxylic acid,
an aldonic acid
– Tollens' reagent (Ag+ in aqueous NH3),
– Fehling's reagent (Cu2+ in aqueous sodium tartrate), and
– Benedicts reagent (Cu2+ in aqueous sodium citrate)
• All three reactions serve as simple chemical tests for what are called
reducing sugars—reducing because the sugar reduces the metal oxidizing
reagent.
• All aldoses are reducing sugars because they contain an aldehyde group,
but some ketoses are reducing sugars as well
 Oxidation of Monosaccharides
• Benedict’s reagent and Tollens’ give positive tests with aldoses
and ketoses.
• The tests are positive even though aldoses and ketoses exist
primarily as cyclic hemiacetals or hemiketals
• In alkaline solution ketoses are converted to aldoses , which are
then oxidized by the cupric complexes
 Oxidation of Monosaccharides
• Carbohydrates that contain only acetal groups do not give positive
tests with Benedict’s or Tollens’ solutions, and they are called
nonreducing sugars
• Glycosides, are non-reducing because the acetal group is not
hydrolyzed to an aldehyde under basic conditions.
 Oxidation of Monosaccharides
• Oxidation of an aldose to a dicarboxylic acid, aldaric acid

• If only the —CH2OH end of the aldose is oxidized without

affecting the —CHO group, a monocarhoxylic acid (uronic
acid) is formed

The reaction must he done enzymatically; no satisfactory chemical

reagent is known that can accomplish this selective oxidation in the
laboratory.
Chain Lengthening: The Kiliani—Fischer Synthesis
• The C1 aldehyde group of the starting sugar becomes C2 of the
chain-lengthened sugar, and a new C1 carbon is added
– Aldoses react with HCN to form cyano-hydrins
– Convertion of the cyanohydrin nitrile group into an aldehyde

•The cyanohydrin is formed

as a mixture of
stereoisomers at the new
chirality center, so two new
aldoses, differing only in
their stereochemistry at C2

•Chain extension of D-
arabinose, for example,
yields a mixture of D-glucose
and D-mannose (Class work)
 Chain Shortening: The Wohl Degradation
❑ The exact opposite of the Kiliani-Fischer sequence
❑ the aldose aldehyde carbonyl group is first converted into a nitrile,
❑ The resulting cyanohydrin loses HCN under basic conditions—the
reverse of a nucleophilic addition reaction
❑ The Wohl degradation does not give particularly high yields of chain-
shortened aldoses, but the reaction is general for all aldopentoses and
aldohexoses
Home tasks
Home tasks

• No plane of symmetry and

not a meso compound.
• So optically active

• Plane of symmetry and

therefore a meso compound.
• So optically inactive
Home tasks

• No plane of symmetry, and

so not a meso compound.
• Thus, optically active

• Plane of symmetry and

therefore a meso compound.
• So optically inactive

D-Allaric acid
Home tasks
 The Eight Essential Monosaccharides
• Human need eight monosaccharides for proper functioning
• All can be biosynthesized from simpler precursors if necessary
• More energetically efficient if obtained from the diet
• Used for the synthesis of
the glycoconjugate
components of Cell Wall.

•NANA is the parent

compound of Sialic acid
•NANA has nine carbons and
is an aldol reaction product of
N-acetylmannosamine with
pyruvate (CH3COCO2-)
0
Cell-Surface
Carbohydrates
Carbohydrates composition of ABO blood group
 Disaccharide
• A disaccharide or biose is the carbohydrate formed when two
monosaccharides undergo a condensation reaction

• There are two different types of disaccharides:

– Reducing disaccharides (e.g. lactose)

– Non-reducing disaccharides (e.g. sucrose)

 Types of disaccharide
• Reducing disaccharides, in which one monosaccharide is a reducing
sugar and has a free hemiacetal unit

– Example: Cellobiose, lactose and Maltose

• Non-reducing disaccharides, in which the components bond through an

acetal linkage between their anomeric centers and neither
monosaccharide has a free hemiacetal unit

– Example: Sucrose and trehalose

Lactose Sucrose
 Most common disaccharide
• Most common disaccharides are:
• Sucrose, lactose, and maltose

• Maltose hydrolyzes to 2 molecules of D-glucose

• Lactose hydrolyzes to a molecule of glucose and a

molecule of galactose

• Sucrose hydrolyzes to a molecule of glucose and a

molecule of fructose
 Common disaccharides

Disaccharide Unit 1 Unit 2 Bond

Sucrose glucose fructose α(1→2)β

Lactulose galactose fructose β(1→4)

Lactose galactose glucose β(1→4)

Maltose glucose glucose α(1→4)

Trehalose glucose glucose α(1→1)α

Cellobiose glucose glucose β(1→4)

 Common disaccharides
Sucrose Lactose
Glucose (α1→2β) fructose Galactose (β 1→4) Glucose
 Common disaccharides
Trehalose Cellobiose
Glucose (α1→1 α) Glucose Glucose (β1→4) Glucose
 Sucrose
• Table sugar (sucrose) comes from plant sources.

• Two important sugar crops predominate:

– sugarcane (Saccharum spp.) and

– sugar beets (Beta vulgaris),

• Sugar can account for 12% to 20% of these

plant's dry weight.
 Sucrose (+66.5o)
❑ -D-glucopyranosido-b-D-fructofuranoside

❑ b-D-fructofuranosido--D-glucopyranoside

• Also known as table sugar

– Commercially obtained from sugar cane or sugar beet

– Sucrose specific rotation +66.5

– Hydrolysis yield glucose (+52.5o) and fructose (–92o) (invert sugar)

• Invert sugar because the sign of optical rotation changes, or inverts, during
the hydrolysis of sucrose ([a]D=66.5) to a glucose/fructose mixture
([a]D =-40).
• Used pharmaceutically to make

syrups, troches
 Lactose
❑ This is a disacchride found in milk
(milk sugar) and is composed of
glucose and galactose
❑ b-D-galactose joined to -D-glucose

via b (1,4) linkage milk contains the

α and β-anomers in a 2:3 ratio

❑ Used in infant formulations, medium

for penicillin production and as a
diluent in pharmaceuticals
 Maltose
• This is a disaccharide composed of 2 glucose units, which is
formed from starch or glycogen by digestion

• 2-glucose molecules joined via (1,4) linkage known as malt

sugar produced by the partial hydrolysis of starch (either
salivary amylase or pancreatic amylase)

• used as a nutrient, sweetener and as a fermentative reagent

 Cellobiose and Maltose

•Cellobiose can't be digested by

humans and can't be fermented
by yeast.
•Maltose, however, is digested
without difficulty and is fermented
readily. Maltose

•Both are reducing sugars (Think

why.)
•We can not digest cellulose
(Why?)

Cellobiose
 Polysaccharides

• PS have one free anomeric —OH group at

the end of a very long chain
– polysaccharides aren't reducing sugars and don't
show noticeable mutarotation
• Types:
-Homopolysaccharides
-Heteropolysaccharides
Polysaccharides
 Cellulose

• Most abundant polysaccharide in nature

• Cellulose molecule is a linear, unbranched
homopolysaccharide, consisting of 10,000 to 15,000 D-
glucose units.
• Cellulose forms extended fibers.
 Starch
Amylose:
•Insoluble in cold water
• Salivary amylase
•Accounts for about 20% by weight of starch • Pancreatic amylase
•Consists of several hundred glucose molecules
linked together by 1—>4- α -glycoside bonds

Amylopectin:
•Soluble in cold water
•Accounts for about 80% by weight of starch
•Amylopectin contains l->6-α-glycoside branches
approximately every 25 glucose units

Source of starch:
Rice, Wheat etc. (energy storage in plant source)
Amylopectin
 Glycogen
❑ Like the amylopectin found in starch, glycogen contains a
complex branching structure with both α(1—>4) and α(1—>6)
links
❑ Glycogen molecules are larger than those of amylopectin up
to 100,000 glucose units and contain even more branches
❑ Frequency of brunching is more than starch (after~12
residues).
❑ Source: Meats (energy storage in animal: liver and muscle)

Glycogen
 Most animal can’t digest cellulose
• Glycogen and starch ingested in the diet are hydrolyzed by α-
amylases and glycosidases, enzymes in saliva and the
intestine that break (α1-4) glycosidic bonds between glucose
units.

• Most animals cannot use cellulose as a fuel source, because

they lack an enzyme to hydrolyze the (β-1-4) linkages.

• Some herbivores also harbor in their intestines of colonies

of bacteria that can digest them for a portion of the
cellulose they eat. The enzymes responsible for this
hydrolysis are called cellulases.
 Chitin
• Chitin is a linear homopolysaccharide composed of N-
acetylglucosamine residues in β-(1-4 ) linkage

• Probably the second most abundant polysaccharide, next to

cellulose, in nature

• The only chemical difference from cellulose is the

replacement of the hydroxyl group at C-2 with an acetylated
amino group.

• Chitin forms extended fibers similar to those of cellulose,

and like cellulose cannot be digested by vertebrates.
 Chitin
N-Acetylglucosamine-N-acetylglucosamine , β-(1-4 )
linkage
• Chitin is the principal component of the
hard exoskeletons of nearly a million
species of arthropods—insects, lobsters,
and crabs.

• The hard crust of chitin protects insects

and shellfish
 Some Other Important Carbohydrates
• Deoxy sugars

• 2-deoxyribose exists in water solution as a complex equilibrium mixture of

both furanose and pyranose forms. The most common deoxy sugar found
in DNA
• Amino sugars