CARBOHYDRATES

STRUCTURE AND CLASSIFICATIONS

• Polyhydroxyaldehyde or polyhydroxyketone, or a substance
that can be hydrolyzed to form these compounds

• Referred to as saccharides (Latin: saccharum, “sugar”).

• Most abundant organic compounds in the plants

• Act as storehouses of chemical energy

• Essential components of nucleic acids

• (D-ribose and 2-deoxy-D-ribose)
• Components of supportive structures in
• Plants (cellulose)
• Crustacean shells (chitin)
• Connective tissues in animals (acidic polysaccharides)
• Carbohydrates are classified depending on the number of
simple sugars they contain:
• Monosaccharides which cannot be hydrolyzed to simpler
carbohydrates
• Oligosaccharides
• Polysaccharides
• Derives from the general molecular formula Cn(H2O)m.
• Glucose (blood sugar): C6H12O6
• Sucrose (table sugar): C12H22O11

• Not all carbohydrates have this general formula.

• Some have insufficient or excess oxygen atoms.
• Some contain nitrogen.
B. Structure and
Nomenclature
Monosaccharides:
• Have the general formula CnH2nOn, where n varies from 3 to 8

• Aldose: a monosaccharide containing an aldehyde group

• Ketose: a monosaccharide containing a ketone group

Monosaccharides:
• Classified by their number of carbon atoms

Name Formula
• Suffix “ose”
Triose C3 H6 O3
Tetrose C4 H8 O4
Pentose C5 H1 0 O 5
Hexose C6 H1 2 O 6
Heptose C7 H1 4 O 7
Octose C8 H1 6 O 8
Monosaccharides:
• There are only two trioses

CHO CH2 OH
CHOH C= O
CH2 OH CH2 OH
Glyceraldehyde D ihydroxyacetone
(an aldotriose) (a ketotriose)
Monosaccharides:
• Can exist in different structural configurations called
“projections” or “conformations”

• These are:
• Fischer
• Haworth
• Chair
Fischer Projections:
• Glyceraldehyde, the simplest aldose, contains a stereocenter
and exists as a pair of enantiomers.

CHO CHO

H C OH HO C H

CH2 OH CH2 OH
Fischer Projections:
• Two-dimensional representation for showing the configuration
of tetrahedral stereocenters
• Horizontal lines represent bonds projecting forward
• Vertical lines represent bonds projecting to the rear

con vert to
CHO a Fischer CHO
projection
H C OH H OH
CH2 OH
CH2 OH
Fischer Projections:
• In 1891, Emil Fischer made the arbitrary
assignments of D- and L- to the enantiomers of
glyceraldehyde.

CHO CHO
H OH HO H
CH 2 OH CH 2 OH
D-Glyceraldehyde L-Glyceraldehyde
25 25
[]D = +13.5° []D = -13.5°
Fischer Projections:
• D-monosaccharide: -OH on its penultimate carbon is on the
right
• L-monosaccharide: -OH on its penultimate carbon is on the
left
CHO CHO
H OH HO H
CH 2 OH CH2 OH
D-Glyceraldehyde L-Glyceraldehyde
25 25
[]D = +13.5° []D = -13.5°
Fischer Projections:
• Most common D-tetroses and D-pentoses

CHO CHO
CHO CHO H OH H H
H OH HO H H OH H OH
H OH H OH H OH H OH
CH2 OH CH2 OH CH2 OH CH2 OH
D -Erythros e D -Threose D -Rib os e 2-D eoxy-D -rib os e
Fischer Projections:
• Three most common D-hexoses

CHO CHO CH2 OH

H OH H OH C=O
HO H HO H HO H
H OH HO H H OH
H OH H OH H OH
CH2 OH CH2 OH CH2 OH
D-Gl u co s e D-Gal acto se D -Fru c to s e
Haworth Projections:
 Hemiacetal (half-acetal)
• Results when alcohol is added to the carbonyl group of an aldehyde
or ketone

• -H of the alcohol adds to the carbonyl oxygen and -OR adds to the
carbonyl carbon
Haworth Projections:
• When both the carbonyl group and the hydroxyl group are in
the same molecule, they can form a cyclic hemiacetal with a 5-
or 6-member ring.

redraw to
O show the -OH 3 2
5
4
3
2
1 an d -CHO clos e 1 H H
H to each oth er 4
C
5 O O-H
O-H O O
4-Hyd roxypentanal H A cyclic hemiacetal
Haworth Projections:
• D-Glucose forms these cyclic hemiacetals

1
CHO red raw to sh ow th e -OH CH2 OH
H OH on carbon-5 close to the 5
H OH
aldeh yd e on carbon-1 O
HO H H C
OH H 1
H OH HO H
5
H OH H OH
CH2 OH
D -Glucose CH2 OH CH2 OH anomeric
carb on
H O H OH
OH (  )
H + H
OH H OH H
HO H HO OH(  )
H OH H OH
-D -Glucopyranose -D -Glucopyranose
(-D -Glucose) ( -D -Glucos e )
Haworth Projections:
• New carbon stereocenter created in forming the cyclic
structure is called an anomeric carbon

• Stereoisomers that differ in configuration only at the anomeric

carbon are called anomers

• Anomeric carbon of an aldose is C-1; most common ketoses is

C-2
Haworth Projections:
• Terminologies:
• α form: -OH on the anomeric carbon is on the side
of the ring opposite from the terminal -CH2OH
(down)
• β form: -OH on the anomeric carbon is on the same
side of the ring as the terminal -CH2OH (up)

HOCH2 O H HOCH2 O OH ()

H H H H
H OH () H H
OH OH OH H
-D -Ribofuranose -2-D eoxy-D -ribofuranose
(-D -Rib os e) (-2-D eoxy-D -rib os e)
Haworth Projections:
• Terminologies:
• Pyranose: 6-member ring sugar containing O

• Furanose: 5-member ring sugar containing O

O O
Furan Pyran
Haworth Projections:
• Aldopentoses also form cyclic hemiacetals
• The most prevalent forms of D-ribose and other pentoses in
the biological world are furanoses

HOCH2 O H HOCH2 O OH ()

H H H H
H OH () H H
OH OH OH H
-D -Ribofuranose -2-D eoxy-D -ribofuranose
(-D -Rib os e) (-2-D eoxy-D -rib os e)
Haworth Projections:
• D-fructose also forms a five-membered cyclic
hemiacetal
1
HOCH2 O CH2 OH
5 H HO 2

H OH( )
HO H 1
CH2 OH
2
 -D -Fructofuranose C=O HOCH2 O OH ( )
( - D -Fructos e) HO H 5 H HO 2
H OH H CH2 OH
5
H OH HO H 1

CH2 OH
D -Fru ctose  - D -Fru ctofu ran os e
(- D -Fructose)
Chair Conformations:
• For pyranoses, the six-membered ring is more
accurately represented as a chair conformation

anomeric
carbon
CH2 OH
HO O
HO
OH()
OH
 -D -Glu copyran os e
( - D -Glucos e)

CH2 OH CH2 OH
HO OH HO O
HO O HO
C
OH H
HO
OH( )
D -Glucos e
- D -Glu copyran os e
(  - D -Glucose)
Chair Conformations:
• In both a Haworth projection and a chair conformation, the
orientations of groups on carbons 1-5 of β-D-glucopyranose
are up, down, up, down, and up

6
CH 2 OH
6
5 O OH()
H 4 CH2 OH
H HO O
4 OH 1
H HO 5
HO H 2 OH( )
3
3 2 OH 1
H OH
-D -Glucop yranose  - D -Glucopyranose
(Haw orth p rojection) (ch air con formation)
 Mutarotation
• The change in specific rotation that accompanies formation of
an equilibrium mixture of α- and β-anomers in aqueous
solution

• α- and β-anomers can have the ring open and then form the
other anomer.
Mutarotation:
Mutarotation:

CH2 OH CH2 OH CH2 OH

HO O HO OH HO O
HO HO O HO
OH C
OH HO HO
H OH
-D -Glucopyranose Open-chain form -D -Glucopyranose
[] D 2 5 = + 18.7° [] D 2 5 = +112°
C. Physical and Chemical
Properties
Monosaccharides:
• Sweet, colorless crystalline solids
• Very soluble in water; slightly soluble in ethanol

S w eetness S w eetness
Relative to Artificial Relative to
Carbohydrate S ucrose Sweetener S ucrose
fructos e 1.74 saccharin 450
sucrose (tab le sugar) 1.00 acesu lfame-K 200
honey 0.97 aspartame 180
glu cose 0.74
maltose 0.33
galactos e 0.32
lactose (milk su gar) 0.16
Glycosides:
• Formed when hemiacetal reacts with alcohol to
give an acetal
anomeric
CH 2 OH carbon
O OH
H +
H H Acetals
OH H + CH3 OH
-H2 O
HO H
H OH glycos idic
CH2 OH bond CH2 OH
-D -Glu copyran os e
O OCH3 H OH
(-D -Glu cose) H
H H
Hemiacetal OH H + OH H
HO H HO OCH3
H OH H OH
Methyl -D -glu copyran os ide Methyl -D -glu copyran os ide
(Methyl -D -glu coside) (Methyl -D -glucos ide)
Glycosides:
• Cyclic acetal derived from a monosaccharide is called a
glycoside

• Bond from the anomeric carbon to the -OR group is called a

glycosidic bond
Glycosides:
 Canbe hydrolyzed in acidic solution to form alcohol
and a monosaccharide

• Mutarotation is not possible:

• Ring can’t open up
• No equilibrium with the open-chain form
D. Oxidation and Reduction
of Simple Sugars
Reduction Products:
• Aldehyde and ketone groups can be reduced to form alcohols

• Carbonyl groups can be reduced to a hydroxyl groups (alditol)

• Requires reducing agents such as NaBH4 (Sodium

Borohydride) or metal H2
Alditols:
• Sorbitol is found in the plant world in many berries and in
cherries, plums, pears, apples, seaweed and algae.

• It is about 60 percent as sweet as sucrose and is used in the

manufacture of candies and as a sugar substitute for diabetics.
Alditols:
• Other common alditols
CH2 OH
HO H CH2 OH
CH2 OH HO H H OH
H OH H OH HO H
H OH H OH H OH
CH2 OH CH2 OH CH2 OH
Erythritol D -Mannitol Xylitol
Oxidation Products:
• Aldehyde group can be oxidized to produce a carboxylic acid.

• Aldehyde group of an aldose is oxidized under basic

conditions to a carboxylate anion called an aldonic acid.

• Any carbohydrate that reacts with an oxidizing agent to form

an aldonic acid is classified as a reducing sugar .
E. Common Dissacharides
Sucrose:
• Most abundant disaccharide in the biological world
• Non-reducing sugar

CH2 OH a unit of -D -

CH2 OH
O glu copyran os e
HO
OH 1 HO 1
HO OH
OH O HOCH2 O a unit of -D -
HOCH2 O fructofuranose
O
HO 2 HO 2

CH2 OH 1
CH2 OH
1
OH OH
Sucrose:
Lactose:
• Principal sugar present in milk; it makes up
about 5 to 8 percent of human milk and 4 to 6
percent of cow's milk.

• Consists of D-galactose bonded by a β-1,4-

glycosidic bond to carbon 4 of D-glucose

CH2 OH
O OH -1,4-glycosid ic bond
OH
4 CH2 OH
CH2 OH OH O CH2 OH
OH O O 4
HO 1 O O
OH 1
OH OH HO OH
OH
OH
Lactose:
Maltose:
• Present in malt, the juice from sprouted barley and other
cereal grains

• Consists of two glucose units joined by an α-1,4-glycosidic

bond
-1,4-glycosid ic
1 4 CH 2 OH CH2 OH b on d
O
HOCH2 O O OH HO
O OH HO 1
OH OH 4 CH2 OH
HO O O
HO HO OH
OH OH
F. Polysaccharides
Polysaccharides:
• Polymer containing many monosaccharide units

• Starch: a polymer of D-glucose

• Two forms: amylose and amylopectin

• Glycogen
• Energy-reserve carbohydrate for animals

• Cellulose
Amylose:
• Composed of unbranched chains of up to 4000
D-glucose units joined by α-1,4 bonds
Amylopectin:
• Contains chains up to 10,000 D-glucose units also joined by α-
1,4-glycosidic bonds

• Branched compound

• New chains of 24 to 30 units attached by α-1,6 linkages

Amylopectin:
Glycogen:
• Branched polysaccharide of approximately 106 glucose units
joined by α-1,4- and α-1,6-glycosidic bonds

• Total amount of glycogen in the body of a well-nourished

adult human is about 350g, divided almost equally between
liver and muscle
Cellulose:
• Chain of D-glucose units joined by β-1,4-glycosidic bonds

• Average chain has approximately 2200 glucose units per molecule.

• Arrangement of parallel chains in bundles gives cellulose fibers

their high mechanical strength.

• Insoluble in water
Cellulose:
• Can not be digested by humans and other
animals except ruminants but can be digested
by many bacteria and microorganisms
G. Blood Group Sugars
Blood Group Sugars:
• Several sugar groups attached to red blood cell (RBC) surface

• Difference in one sugar accounts for ABO blood type.

Blood Group Sugars:
Blood Group Sugars:
 GLYCOBIOLOGY

GLYCOCONJUGATES - biologically active molecules

made up of informational carbohydrates covalently
joined to a protein or a lipid
 GLYCOCONJUGATES:
Proteoglycans (95% CHO)
- macromolecules of the cell surface or extracellular matrix.
- glycosaminoglycan moiety dominates the structure and is the main
site of biological activity .
- has multiple binding sites via H-bonding and electrostatic interactions.
Glycoproteins
- have one or several oligosaccharides covalently joined to a protein
- found on the outer face of plasma membrane, in the extracellular
space, in the blood, membranes of organelles (lysozomes, golgi
complexes, secretory granules)
- highly specific sites for recognition and high-affinity binding by other
proteins.
Glycolipids
- membrane lipids in which the hydrophilic head groups are
oligosaccharides.
- specific sites for recognition by CHO-binding proteins.
Tissues are not made up solely of cells. Substantial
part of their volume is extracellular space , largely
filled by an intricate network of macromolecules
constituting the :

EXTRACELLULAR MATRIX

Glycosaminoglycan or GAG found covalently linked

to proteins in the form of PROTEOGLYCAN

Fibrous Proteins : Collagen, elastin, fibronectin

and laminin
Glycosaminoglycans (GAGs) are unbranched
polysaccharides consisting of alternating
hexosamine and hexuronic residues which
carry sulfate groups in different positions.

The chondroitin sulfate family

includes seven sub-types
The known GAGS are designated unsulfated chondroitin
chondroitin sulfate, sulfate, oversulfated chondroitin
sulfate and chondroitin sulfates
keratan sulfate, A-E which vary in the number and
dermatan sulfate, position of their sulfate functional
groups. Chondroitin sulfate A is
hyaluronic acids, also known as chondroitin 6-
heparin and sulphate, chondroitin sulfate B is
also known as dermatan sulphate,
heparan sulfate. and chondroitin sulfate C is also
known as chondroitin 4-sulphate.
 Glycosaminoglycan & Proteoglycans are
Components of the Extracellular Matrix

Extracellular matrix ( or ground substances) are gel-like

material that:
- fills the extra-cellular space in animal tissues.
- holds cells of tissues together
- provides a porous pathway for the diffusion of nutrients
and oxygen to individual cells.
- composed of the interlocking meshwork of
heteropolysaccharides and fibrous proteins.
Common Heteropolysaccharide (Glycosaminoglycan)
Components of
Extracellular Matrix

The ionized
carboxylate and
sulfate groups gives
these polymers their
characteristic high
negative charge.

To minimize repulsive
forces of the negative
charges , the molecules
assume an extended
conformation in soln.
- this explains the very
high viscosity of soln of
this long thin molecules.
Proteoglycan structure, linked to a Trisaccharide Bridge

 A typical trisaccharide linker connects a glycosaminoglycan to

a serine residue in the core protein
 A xylose residue at the reducing end of the linker is joined by its
anomeric carbon to the hydroxyl of the serine.

 The Ser residue is generally in the sequence -Ser-Gly-X-Gly-

although not every protein has an attached glycosaminoglycan.
A proteoglycan aggregate of the extracellular matrix

Supramolecular
assembly of many
aggrecan core
proteins bound to a
single molecule of
hyaluronate.

Aggrecan strongly
interacts with the
collagen in the
extracellular matrix
of cartilages -
contributing to its
development and
tensile strength.
Fibrous matrix proteins (collagen, fibronectin and elastin)
are interwoven with the extracellular matrix, forming a cross-
linked meshwork which gives the extracellular matrix
strength and resilience

This involves electrostatic interactions between the sulfate

and/or carboxylate groups of the proteoglycan complex and
the basic side chains in collagen and the other proteins.

 Fibronectin has separate domains that bind, fibrin, heparan sulfates,

collagen and integrins
 Integrins have binding site for a number of other extracellular
macromolecules. They mediate signaling between the cell interior and
the extracellular matrix.

An array of interactions between cellular and

extracellular molecules.
Interaction between the cell and extracellular matrix

- Association between the

cells and proteoglycan of
the extracellular matrix is
mediated by a membrane
protein ( integrin) and by
an extracellular protein
(fibronectin).
- Proteoglycan and
fibronectin are closely
associated with collagen
fibers.
Proteoglycans in the Extracellular Matrix of the Rat Cartilage

Core protein

GAG

The tissue was rapidly frozen at -196 C, fixed and stained while still frozen
(freeze substitution) to prevent the GAG chains from collapsing. The
proteoglycans form a filamentous network where a single striated collagen
fibril is imbedded (Alberts)
 SOME COMMON PROTEOGLYCANS

PROTEOGLYCAN

Aggrecan

Betaglycan

Decorin

Perlecan

Syndecan

Dally (in
Drosophila)
Alberts, The Cell
 BACTERIAL CELL WALL

o Rigid -> characteristic shapes

o Allows bacteria to live in hypotonic environment
( < intracellular salt concn)
o Responsible for bacterial virulence ( disease-evoking power)
Protects bacteria from lysis in the host cell
o Contains characteristic antigen (immunological markers)
ex. O-antigen of gram-negative bacteria
Lipopolysaccharides
Injection of bacterial cell wall preparations into animals can invoke
immunity against the bacteria.

BACTERIA are classified as gram positive or gram

negative depending on whether or not they take
up gram stain
BACTERIAL CELL WALL HAVE A PEPTIDOGLYCAN
FRAMEWORK

Cell walls of both gram-positive and gram-negative

bacteria consists of covalently linked polysaccharide
and polypeptide chains which form a baglike
molecule that completely encases the cell.

Linear chains of alternating N-acetylglucosamine (NAG), B(1-

4) –linked to N-acetylmuramic acid (NAM).
 NAM’s lactic acid residue forms amide bond with
tetrapeptide to form peptidoglycan repeating unit.
Neighboring parallel peptidoglycan chains covalently cross-
linked via a pentaglycine chain
 Bacterial Cell Wall Contains Heteropolysaccharide

Peptidoglycan of the cell wall of

the gram-positive bacterium
Staphylococcus aureus.

Lysozyme hydrolyzes the

glycosidic bonds between MurNac
and GlcNac

- present in tears, defense against

bacterial infection of the eye.
- also produced by certain
bacterial viruses to ensure their
release from the host bacteria, an
essential step in the viral
infection cycle
Cell Wall of Gram Positive Bacteria :Staphylococcus aureus

The D-amino acids of peptidoglycans provides resistance to protease

 Gram Negative Bacterial Cell Wall

Gram-negative bacterial cell wall also contain peptidoglycan, but it is

single-layered and covered by an outer lipid membrane layer.

This difference accounts for the different staining properties of

Gram(+) and Gram (-) bacteria and the differential sensitivity to
different antibiotics.
Glycoproteins Are Information-Rich Conjugates
Containing Oligosaccharides
 Proteins secreted by eukaryotic cells :
- immunoglobulins (antibodies)
- hormones (follicle-stimulating hormone, luteinizing
hormone, thyroid stimulating hormone)
 Milk proteins: lactalbumin
 Proteins secreted by the pancreas: ribonuclease
 Integral proteins of plasma membrane function as:
- receptors for cpds in circulation (hormones)
- mediator of interaction between cells.
 Proteins of endoplasmic reticulum and golgi apparatus
 Serum and mucus proteins
The biological advantage of adding
oligosaccharides to proteins

 The hydrophilic clusters of CHO alter the

polarity and solubility (conformation) of the
proteins with which they are conjugated.

 The oligosaccharide chains attached to the

newly synthesized proteins in the ER and Golgi
complex may influence the polypeptide –folding
events and determine the tertiary structure of
the protein.
In summary, the functions of CHO chains of
the glycoproteins are diverse:

• stabilize the protein against denaturation

• protect it from proteolytic degradation
• enhance its solubility
• serve as recognition signals to facilitate cell-cel
interaction
  When numerous negatively charged
oligosaccharide chains are clustered in a single
region of the protein, the charge repulsion
favors the formation of extended , rod-like
structure.

 The bulkiness and negative charges of

oligosaccharides also protects some proteins
from attack by proteolytic enzymes.
Oligosaccharide Linkages in Glycoproteins

O-linked glycosidic bond to the hydroxyl N-linked glycosidic bond to the amide
(-OH) grp of Ser or Threonine. N of Asn residue.
N-linked Glycoproteins Exhibit Numerous Glycoforms

- variant species that differ in sequences, locations

and numbers of its covalently attached
oligosaccharides

Ex: Bovine Ribonuclease B ( RNase

B) has a single N-linked
oligosaccharide chain. Core sequence
has considerable
microgeheterogeneity. Mannose NAG
vs CHO-free enzyme RNase A

Oligosaccharide does not appear to Core Sequence

affect conformation,substrate
specificity, or catalytic activity.
O-Linked Glycoproteins - Protective Functions

• O-linked CHO are not uniformly distributed along the polypeptide

chain.
• Clustered into heavily glycosylated (65-85% CHO by wt.)
sergents ( Ser & Thr 20 to 40% of the aa sequence).
• CHO hydrophilic and steric interactions cause the heavily
glycosylated region to assume extended conformation.

Mucins: large O-linked glycoprotein (protein comp of mucus)

• CHO are sulfated and mutually repelling.

• Consists of stiff chains with random coil conformations that
occupy time averaged volumes approx thoseof small bacteria.

Thus , mucins, at physiological concentration, form intertangled

networks that comprise the viscoelastic gels which protect and
lubricate the mucous membrane that secrete them.
Oligosaccharide Biomarkers Mediate a Variety of
Intercellular Interactions
A. CHO Groups of Membrane-bound Glycoproteins are located on
the external surface of cell membrane

- Base on electron microscopy: GP labeled with lectins

conjugated with ferritin ( electron dense iron hydroxide core)
- Important for intercellular comunication and not for
intracellular “housekeeping”

B. Oligosaccharides-lectin interaction mediate many

biological processes
Lectin - proteins found in all organisms
- bind CHOs with high specificity and affinity.
- can recognize critically situated hydrogen-bonding
partners in its CHO recognition domain.
- serve in a variety of cell-cell recognition and adhesion
process.
Roles of Oligosaccharides in Recognition and Adhesion
in the Cell surface
Glycolipids and Lipopolysaccharides Are
Membrane Components

From E. coli

S. typhimurium

Gangliosides Bacterial Lipopolysaccharide

Lipopolysaccharides
 Dominant surface feature of the outer membrane of the gram
negative bacteria such as E. coli and Salmonella typhimurium.

 Prime targets of the antibodies produced by verterbrate

immune system in response to bacterial infection

 Important determinants of the serotype of bacterial strains

(serotypes are strains that are distinquished on the basis of
antigenic properties)

 S. Typhimurium has six fatty acids bound to two glucosamine

residues, one of which is the point attachment of the complex
oligosaccharide. E. Coli has similar unique structure

 Some are toxic to human and other animals. Gram – negative

bacterial infections can dangerously lower blood pressure that
accompany toxic shock syndrome.