CARBOHYDRATES

INTRODUCTORY BIOCHEMISTRY
 CARBOHYDRATES

• Carbohydrates (“hydrate of carbon”) have empirical formulas

of (CH2O)n , where n ≥ 3
• Monosaccharides one monomeric unit
• Oligosaccharides ~2-20 monosaccharides
• Polysaccharides > 20 monosaccharides
• Glycoconjugates linked to proteins or lipids

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 MONOSACCHARIDES
Aldoses and Ketoses

• Aldoses - polyhydroxy aldehydes

• Ketoses - polyhydroxy ketones
• Trioses (3 carbon sugars) are the smallest monosaccharides

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 MONOSACCHARIDES
Fisher projections of trioses

• Aldehyde C-1 is drawn at the top of a

Fischer projection
• Glyceraldehyde (aldotriose) has a chiral
centre (C-2 carbon has 4 different groups
attached to it)
• Dihydroxyacetone (ketotriose) does not
have an asymmetric or chiral carbon and is
not a chiral compound

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 MONOSACCHARIDES
Fisher projections of 3 to 6 carbon D-aldoses

• D-sugars have the same configuration as D-Dlyceraldehyde in their chiral carbon most
distant from the carbonyl carbon
• Aldoses shown blue (next slide) are most important in biochemistry

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Fisher projections of the 3 to 6 carbon D-aldoses (blue structures are most common)

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Fisher projections of the 3 to 6 carbon D-ketoses (blue structures are most common)

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 MONOSACCHARIDES
Characteristics

• Hexoses are the most abundant monosaccharides

• Aldopentoses are important components of nucleic acids
• Derivatives of trioses and heptoses are important intermediates in carbohydrate
metabolism
• All simple monosaccharides are white crystalline solids that are freely soluble in water,
but insoluble in nonpolar solvents
• Most have a sweet taste

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 MONOSACCHARIDES
Stereoisomers
• Stereoisomers have the same molecular formula and the same structure, but differ in
their configuration (the arrangement of their atoms in space)

Geometrical (cis-trans)
Stereoisomers
Optical isomerism

• Optical isomerism occurs in molecules which contain one or more asymmetric

carbon atoms (chiral centers)

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 MONOSACCHARIDES
Stereoisomers
• All of monosaccharides except dihydroxyacetone contain one of more asymmetric
carbon atoms

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 MONOSACCHARIDES
Stereoisomers
• D- and L-Glyceraldehydes are the reference or parent compounds for designating the
absolute configuration of all stereoisomeric compounds
• Chiral molecules are optically active, i.e. they rotate the plane of polarized light
• The convention of designating D- and L- stereoisomers was originally based on the
optical properties of glyceraldehyde
• The form of glyceraldehyde that caused rotation to the right (dextrorotatory) was
designated D; the form that caused rotation to the left (levorotatory) was designated L
• Longer aldoses and ketoses can be considered as extensions of glyceraldehyde and
dihydroxyacetoene, respectively, with chiral H-C-OH groups inserted between the
carbonyl carbon and the primary alcohol group

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 MONOSACCHARIDES
Enantiomers

• Enantiomers - pairs of D-sugars and L-sugars

• Aldoses and ketoses of the L series are mirror
images of their D counterparts
• 2n represents the number of possible optical
isomers, where n is the number of asymmetric
carbon atoms

• D sugars predominate in nature

• L sugars are also found in nature (L-Fucose and L-Rhamnose)

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 MONOSACCHARIDES
Epimers
• Epimers - sugars that differ at only one of several chiral centers

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 MONOSACCHARIDES
Cyclization of Aldoses and Ketoses
Mutarotation and anomers
• In aqueous solution, many monosaccharides act as if they had one more asymmetric
center than is given by the open chain (Fisher projection) structural formulas
• Glucose may exist in 2 different isomeric forms differing in their specific rotation: α-D-
Glucose and β-D-Glucose

Properties α-D-Glucose β-D-Glucose

Specific rotation [α]20 +112.2ο +18.7ο
Melting point, οC 146 150
Solubility in H2O, g per 100ml 82.5 178
Relative rate of oxidation by 100 <1.0
glucose oxidase
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 MONOSACCHARIDES
Cyclization of Aldoses and Ketoses
Mutarotation and anomers
• When the α and β isomers of D-Glucose are dissolved in water, the optical rotation of
each gradually changes with time and approaches a final equilibrium value of [α]20D =
+52.7º
• The change called mutarotation is due to the formation of an equilibrium mixture
consisting of about 1/3 α-D-Glucose and 2/3 β-D-Glucose at 20οC
• The α and β isomers of D-Glucose are not open chain structures, but six-membered
ring structures formed by the reaction of the alcoholic –OH at C5 with the aldehydic C1

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 MONOSACCHARIDES
Cyclization of Aldoses and Ketoses
Pyran and furan ring systems
• A six-membered sugar ring is a “pyranose”

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 MONOSACCHARIDES
Cyclization of Aldoses and Ketoses
Pyran and furan ring systems
• A five-membered sugar ring is a “furanose”

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 MONOSACCHARIDES
Cyclization of Aldoses and Ketoses
Reaction of an alcohol with:
a) An aldehyde to form a hemiacetal

a) A ketone to form a hemiketal

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 MONOSACCHARIDES
Cyclization of Aldoses and Ketoses
• D-Glucopyranose is an intramolecular hemiacetal in which the –OH group at C5 has
reacted with the aldehydic C1, rendering it asymmetric
• D-Glucopyranose can exist in 2 different stereoisomers designated α and β
• Isomeric forms of monosaccharides that differ from each other only in configuration
about the carbonyl carbon atom are anomers and the carbonyl carbon is called the
anomeric carbon, which is the most oxidized carbon

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 MONOSACCHARIDES
Cyclization of Aldoses and Ketoses
Cyclization of D-Glucose to form α-D-Glycopyranose and β-D-Glycopyranose

C-5 hydroxyl close to

aldehylde group

Reaction of C-5 hydroxyl

with one side of C-1
gives α, reaction with
the other side gives β
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 MONOSACCHARIDES
Cyclization of Aldoses and Ketoses
Cyclization of D-Ribose to form α- and β-D-Ribopyranose and α- and β-D-Ribofuranose

Continued on next slide

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 MONOSACCHARIDES
Derivatives
• Many sugar derivatives are found in biological systems
• Some are part of monosaccharides, oligosaccharides or
polysaccharides
• These include
o sugar phosphates
o deoxy sugars
o amino sugars
o sugar alcohols
o sugar acids
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 MONOSACCHARIDES
Sugar Phosphates
• Monosaccharides are often converted to phosphate esters by a reaction with ATP
• These are important intermediates in metabolic pathways

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 MONOSACCHARIDES
Deoxy Sugars
• In deoxy sugars, a hydrogen atom replaces an OH

- Most abundant deoxy sugar

- Important building block of DNA

- L-Fucose and L-Rhamnose (6-deoxy-L-mannose)

are important components of some bacterial
cell walls

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 MONOSACCHARIDES
Sugar Alcohols
• The carbonyl oxygen of monosaccharides can be reduced by H2 gas in the presence of
metal catalysts or by enzymes to form the corresponding sugar alcohol (polyhydroxy
alcohol)

Important components of lipids Component of

FMN and FAD

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 MONOSACCHARIDES
Sugar Acids (1/3)
• Sugar acids are carboxylic acid
• Produced from aldoses by:
Oxidation of C-1 to yield an aldonic acid
Oxidation of the highest numbered carbon to an alduronic acid

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 MONOSACCHARIDES
Sugar Acids (2/3)
Aldonic acids
• D-Glucose yields D-Gluconic acid, which in its
phosphorylated form in an important intermediate
in CHO metabolism

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 MONOSACCHARIDES
Sugar Acids (3/3)
Uronic acids
• D-Glucose yields D-Glucuronic acid
• Uronic acids are very important
biologically (D-Galacturonic acid and D-
Mannuronic acid)

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 REDUCING SUGARS
• If a sugar has a free aldehyde group or a group that can readily convert to an aldehyde
group (e.g. fructose), it will act as a reducing agent in alkaline solution and will be
oxidized to a sugar acid
• The reagents designed to test for a reducing sugar include a mixture of cupric ions
(Cu2+; blue) in a basic solution that will react with the reducing sugar to form cuprous
ions (Cu+; red precipitate)

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 MONOSACCHARIDES
Amino Sugars (1/4)
• An amino group replaces a monosaccharide OH
• Amino sugars of glucose and galactose occur commonly in glycoconjugates

H–C O H–C O
H – C – NH2 H – C – NH2
OH – C – H OH – C – H
H – C – OH OH – C – H
H – C – OH H – C – OH
CH2OH CH2OH

D-Glucosamine D-Galactosamine

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 MONOSACCHARIDES
Amino Sugars (2/4)
• The amino group is sometimes acetylated

N-Acetyl-α-D-glucosamine
Major component of chitin, a
structural polysaccharide found
in the exoskeletons of insects
and crustaceans
N-Acetyl-α-D-galactosamine
Component of glycolipids and
chondroitin sulfate, major
polysaccharide of cartilage
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 MONOSACCHARIDES
Amino Sugars (3/4)
• Muramic acid and Neuraminic acid are important building blocks of the structural
polysaccharides found the cell walls of bacteria and the cell coats and membranes of
higher animal cells, respectively

N-Acetylmuramic acid
N- Acetyl-D-glucosamine and
lactic acid
N-Acetylneuraminic acid
N- Acetyl-D-mannosamine and pyruvic acid
(Sialic Acid)
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 DISACCHARIDES AND OTHER GLYCOSIDES
Glycosidic Bonds
• A Glycosidic bond is formed by the reaction of the anomeric carbon of a
monosaccharide with a hydroxyl group of another monosaccharide to yield
disaccharides
• Oligosaccharides and polysaccharides are chains of monosaccharides joined by
glycosidic bonds
• Glucosides - glucose provides the anomeric carbon
• Glycosides are hydrolyzed by enzymes called glycosidases, which differ in their
specificity according to the type of glycoside bond (alfa or beta), the structure of the
monosaccharide units, and the structure of the alcohol

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 DISACCHARIDES AND OTHER GLYCOSIDES
Glycosides
D-Glucose with methanol yields a glycoside
• In this acid-catalyzed condensation reaction, the anomeric –OH group of the hemiacetal
is replaced by an –OCH3 group, forming methyl glucoside, an acetal

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 DISACCHARIDES AND OTHER GLYCOSIDES
Structures of Disaccharides
• The most common oligosaccharides in nature are disaccharides
• Disaccharides consist of two monosaccharides joined by a glycosidic bond
• In the systematic description of a disaccharide, we must specify:
• Linking atoms
• Configuration of the glycosidic bond
• Name of each monosaccharide residue

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 DISACCHARIDES AND OTHER GLYCOSIDES
Structures of Disaccharides
Maltose (1/2)
• Maltose is present in malt
• It is formed as an intermediate product of
the action of amylases on starch

• It contains two D-Glucose molecules linked by α(1à4) glycosidic bond

• The 2nd glucose molecule contains a free anomeric –OH group than could
exists in α or β:
• It undergoes mutarotation
• Reducing sugar

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 DISACCHARIDES AND OTHER GLYCOSIDES
Structures of Disaccharides
Maltose (2/2)

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 DISACCHARIDES AND OTHER GLYCOSIDES
Structures of Disaccharides
Cellobiose
• Repeating disaccharide unit of cellulose
• It contains two D-Glucose molecules linked by β(1à4) glycosidic bond
• It undergoes mutarotation
• It is a reducing sugar

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 DISACCHARIDES AND OTHER GLYCOSIDES
Structures of Disaccharides
Lactose (1/2)
• Most abundant carbohydrate in milk (5% milk)
• Contains D-Glucose and D-Galactose units linked by β(1à4) glycosidic bond
• It undergoes mutarotation
• It is a reducing sugar

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 DISACCHARIDES AND OTHER GLYCOSIDES
Structures of Disaccharides
Lactose (2/2)
• Infants have the intestinal enzyme lactase that hydrolyzes lactose to its component
monosaccharides for absorption into the bloodstream
• Many adults have low levels of this enzyme and consequently much of the lactose they
drink move through their digestive track to the colon where its bacterial fermentation
produces large quantities of CO2, H2 and irritating organic acids

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 DISACCHARIDES AND OTHER GLYCOSIDES
Structures of Disaccharides
Sucrose (1/2)
• Sucrose is the table sugar and is synthesized only
in plants
• Contains β-D-Fructose and α-D-Glucose units
linked by α,β(1à2) glycosidic bond

• Unlike most disaccharides and oligosaccarides, sucrose contains no free

anomeric carbon atoms:
• It does not undergo mutarotation
• It is a nonreducing sugar
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 DISACCHARIDES AND OTHER GLYCOSIDES
Structures of Disaccharides
Sucrose (2/2)
• Sucrose is much more readily hydrolyzed than other disaccharides
• The hydrolysis of sucrose to D-Glucose and D-Fructose is often called
inversion
Sucrose D-Glucose + D-Fructose

• The mixture is called the invert sugar

• The hydrolysis of sucrose is also catalyzed by invertase and can be followed
with a polarimeter

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 Nucleosides and other Glycosides

• Anomeric carbons of sugars can form glycosidic linkages with alcohols, amines and thiols
in an appropriate solvent
• Aglycones are the groups attached to the anomeric sugar carbon

N-Glycosides
• Nucleosides attached via a ring
nitrogen in a glycosidic linkage as in
guanosine

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 Nucleosides and other Glycosides
O-glycosides

• Digoxin is made up of digoxigenin and digitoxose

• Extracted from the leaves of foxglove plant
Digoxin • A potent stimulant of the heart muscle

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 POLYSACCHARIDES
Classes of Polysaccharides

• Polysaccharides (also called glycans) differ from each other in the nature of their
recurring monosaccharide units, the length of their chains, the types of bonds linking
the units, and in the degree of branching
• Homoglycans - homopolysaccharides containing only one type of monosaccharide
• Heteroglycans - heteropolysaccharides containing residues of more than one type of
monosaccharide
• Most polysaccharides can be classified according to their biological roles

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46
 POLYSACCHARIDES
Storage Homoglycans
Starch and Glycogen
• D-Glucose is stored intracellularly in polymeric forms
• Polymer of α(1à4)-linked subunits of glucose, with
α(1à6)-linked branches
• Plants and fungi – starch
• Animals – glycogen (more extensively branched and
more compact than starch)

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 POLYSACCHARIDES
Storage Homoglycans
Starch
• Starch is a mixture of amylose (unbranched, 100-1,000 D-glucose residues) and
amylopectin (branched, 300-6,000 D-glucose residues)

Structure of amylose
- Linear polymer
- Gives blue color with iodine
- MW up to 500,000 Da
- Assumes a left-handed
helical conformation in
water

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 POLYSACCHARIDES
Storage Homoglycans
Starch
Structure of amylopectin
- Branching occurs once every 25 residues and the branch contains 15-25 residues
- Gives red violet color with iodine
- MW up 100 million Da

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 POLYSACCHARIDES
Storage Homoglycans
Glycogen
• Abundant in the liver (10% of wet weight) and skeletal muscles (1-2%)
• Much larger than amylopectin (about 50,000 D-glucose residues)
• More highly branched than amylopectin; branching occurs once every 8-12 glucose
residues

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 POLYSACCHARIDES
Storage Homoglycans
Starch and Glycogen
• Starch and glycogen are hydrolyzed by α- and β-
amylases, both cleave α(1à4) glucosidic bonds
• α-Amylase in an endoglucosidase found in saliva
and pancreatic juices
• β-Amylase is an exoglucosidase found in plants
and removes successisve maltose units from the
nonreducing ends
• Limit dextrin Action of α- and β-amylases

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 POLYSACCHARIDES
Structural Polysaccharides in Plants
Cellulose (1/3)
• Linear unbranched polymer of 300-15,000 D-Glucose units linked by β(1à4) glucosidic
bond. MW range 50,000 to 2,500,000 Da
• The most abundant structural polysaccharide in the plant world. It accounts for over 50%
of the organic matter in the biosphere

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 POLYSACCHARIDES
Structural Polysaccharides in Plants
Cellulose (2/3)
• Digested by cellulase (β-glucosidase), which is not secreted in the digestive tract of most
mammals. It cannot be used as food
• Ruminants (cows and sheep) are exception and can use cellulose as food. The bacteria in
their rumen form the enzyme cellulase

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 POLYSACCHARIDES
Structural Polysaccharides in Plants
Cellulose (3/3)
• Present in the cell walls of plants as cellulose microfibrils, linked by strong Intra- and
interchain hydrogen bonds, giving cellulose its strength and rigidity

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 POLYSACCHARIDES
Structural Polysaccharides in Plants
Hemicelluloses
• Heteropolymers present in most plant cell walls such as xylan, arabinoxylan, and
xyloglucan
• They are not structurally related to cellulose and are referred to as cellulose-linked
glycans. They have different types of sugars, linkages and bonds

Xyloglucan
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 POLYSACCHARIDES
Structural Polysaccharides in Plants
Pectins
• Pectins are present in the primary cell walls of plants and in the middle lamella
• There are different types of pectins, including homogalacturonan, rhamnogalacturonan,
and others. They bind calcium in plant cells

Homogalacturonans

• It is mainly used in food as a gelling agent and stabilizer, among others

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 POLYSACCHARIDES
Structural Polysaccharides in Bacteria
• Bacteria are classified into:
– Gram positive (cell walls contain very little lipids) e.g. Streptococcus
– Gram negative (cell walls rich in lipids) e.g. E. coli
• Bacterial cell walls are different in having varying levels of peptides, proteins, lipids, and
carbohydrates
• They are similar in that the peptide and carbohydrate part are arranged in a common
structural framework, which is a grid like network of polysaccharide chains covalently
cross-linked to each other via small peptide bridges, referred to as peptidoglycans

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 POLYSACCHARIDES
Structural Polysaccharides in Bacteria
Peptidoglycans (1/4)
• The polysaccharide (heteroglycan) moiety is composed of composed of repeating
disaccharide units consisting of GlcNAc and N-acetylmuramic acid (MurNAc) with β(1à4)
linkages connecting the units. Successive units are also attached by β(1à4) linkages

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 POLYSACCHARIDES
Structural Polysaccharides in Bacteria
Peptidoglycans (2/4)
• The peptide moiety consists of a tetrapeptide and a pentapeptide

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 POLYSACCHARIDES
Structural Polysaccharides in Bacteria
Peptidoglycans (3/4)
• Peptidogylcan synthesis (Staphylococcus
aureus): The cross-linking is catalyzed by
a transpeptidase, the enzyme that
penicillins inhibit
• Penicillinase, secreted by resistant
bacteria, converts penicillin to
penicillinoic acid

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 POLYSACCHARIDES
Structural Polysaccharides in Bacteria
Peptidoglycans (4/4)
• Penicillin structure resembling -D-Ala-D-Ala
is shown in red

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 POLYSACCHARIDES
Structural Polysaccharides in Animals
Chitin
• Linear homopolysaccharide composed of N-acetylglucosamine (GlcNAc) residues in
β(1à4) linkage
• Principal component of the hard
exoskeletons of many arthopods
(insects, lobsters, crabs, etc.)
• 2nd most abundant
polysaccharide in nature
(≈1billion tons produced each
year in the biosphere)

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 POLYSACCHARIDES
Structural Polysaccharides in Animals
Cell coats
• The cells in the tissues of vertebrates are not surrounded by a rigid cell wall
• They do have an outercoat that is in some respect comparable to cell walls
• The major components of cell coats of animals are:
Glycolipids
Glycoproteins
Glycosaminoglycans

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 POLYSACCHARIDES
Glycosaminoglycans
• Heteropolysaccharides of the extracellular matrix (ECM), unique to animals and bacteria
and are not found in plants
• Family of linear polymers composed of repeating disaccharide units
• They are so named because of the presence of amino sugars (usually the N-acetyl forms
of D-glucosamine and D-galactosamine)
• They are also characterized by the presence of negatively charged –COO- (sugar acids)
and –OSO3- groups

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 POLYSACCHARIDES
Glycosaminoglycans
• Glycosaminoglycans do not occur in the free state, but associated mainly with proteins to
form proteoglycans

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 POLYSACCHARIDES
Glycosaminoglycans
• Important glycosaminoglycans in carbohydrates:
Hyaluronic acid
Chondroitin sulfate Found in the proteoglycans of
connective tissues
Keratan sulfate
Heparin

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 POLYSACCHARIDES
Glycosaminoglycans
Hyaluronic acid (1/2)
Repeating disaccharide

GlcA = D-glucuronate
GlcNAc = N-acetylglucosamine

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 POLYSACCHARIDES
Glycosaminoglycans
Hyaluronic acid (2/2)
• Composed of 250-25,000 linked disaccharide units
• Primary components of the ground substance of connective tissues
• Present in the synovial fluid, a viscous packing around bone joints serving as
lubricant and shock absorber
• Present in the vitreous humor of the eye and the umbilical cord
• Certain pathogenic bacteria secrete hyaluronidases as well as snake venoms
and insect venoms

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 POLYSACCHARIDES
Glycosaminoglycans
Chondroitin sulfate (1/2)
Repeating disaccharide

GlcA = D-glucuronate
GalNAc4SO3- = N-acetylgalactosamine-4-sulfate

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 POLYSACCHARIDES
Glycosaminoglycans
Chondroitin sulfate (2/2)
• Similar to hyaluronic acid in having alternating ß(1→3) and ß (1→4) and the presence N-
acetylamino sugar
• They have negatively charged sulfate groups on C4 of the amino sugar (chondroitin-4-
sulfate or chondroitin A) or on C6 (chondroitin-6-sulfate or chondroitin C)
• The length of chondroitin sulfate ranges from 15-150 disaccharide units
• Chain length and extent of sulfation may be affected by age of tissue and may be related
to some disease conditions

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 POLYSACCHARIDES
Glycosaminoglycans
Keratan sulfate (1/2)
Repeating disaccharide

Gal = D-galactose
GlcNAc6SO3- = N-acetylglucosamine-6-sulfate
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 POLYSACCHARIDES
Glycosaminoglycans
Keratan sulfate (2/2)
• Similar to hyaluronic acid in having alternating ß(1→3) and ß (1→4) and the
presence N-acetylamino sugar
• GlcNAc is sulfated at C6
• Chain length 10-15 dissaccharide units
• In addition to the dissacchride units it contains a small amount of fucose,
mannose, scialic acid and GlcNAc

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 POLYSACCHARIDES
Glycosaminoglycans
Heparin
• A natural anti-coagulant that binds strongly to antithrombin III (a protein involved in the
terminating and clotting process) and inhibits blood clotting
• In contrast to other glycosaminoglycans, it is not a constituent of connective tissue, but
found in the mast cells that line arterial walls, especially in liver, lungs, and skin
• It is administered intravenously to patients during and after surgery
• It is heterogeneous and made of at least 4 sugar derivatives: D-glucuronic acid, L-
iduronic acid, D-glucosamine, N-acetylglucosamine

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