Carbohydrates

Structure, Function and Types

 Carbohydrates are hydrates of carbon

 Polyhydroxy aldehydes or ketones

 Carbo are also called “Saccharides” - (Greek saccharon = sugar )

 “hydrate of carbon” : composed of carbon and water and have

a composition of (CH2O)n, )
 Ratio - C: H: O is 1:2:1
eg: glucose - C6H12O6 / (CH2O)6 / C6(H2O) 6

 Some carbohydrates also contain nitrogen, phosphorus or

sulfur.

 Widely distributed in both animal and plant tissues.

 The most abundant constituents of living matter.

 Biological importance of Carbohydrates

1. Source of energy
Most commonly used - glucose.

2. Energy storing
 In animals excess glucose stored as glycogen in liver and
muscle / plants as starch
 Starch - the major dietary carbohydrate for man
 liver glycogen is used during fasting or starvation to
replenish the blood glucose
 Muscle, glycogen used to provide energy during exercise.
 Biological importance of Carbohydrates

3. Structural function
Plants : cellulose
Arthropods : chitin
Humans : proteoglycans, glycoproteins and glycolipids
connective tissues /cell membranes
Bacteria : peptidoglycans in cell membranes

4. important intermediates in various metabolic

pathways
eg. : Glucose-6-phosphate
Glyceraldehydes – 3 – phosphate
 Biological importance of Carbohydrates
5. Immunologically significant groups
blood group antigens / cell surface antigens.

6. Receptor sites for hormone recognition

Glycoprotein on the surface of liver /fat cells receptor for
insulin.

7. Components of important compounds in the cells

RNA /coenzymes - ribose & DNA - deoxyribose.

8. Medicinal importance
Some antibiotics contain carbohydrates.
 Classification of carbohydrates
Three main groups :
Monosaccharides | Disaccharides | Polysaccharides

Monosaccharides
Simplest sugars : can not be hydrolyzed further

Disaccharides :
Two monosaccharide units

Oligosaccharides :
3-10 monosaccharide units

Polysaccharides :
Many molecules of monosaccharides
 Common monosaccharides
Galactose
Glucose
• Hardly tastes sweet
•Mild sweet flavor
• Hydrolysis of lactose
•Known as blood sugar

1. Most have a sweet taste

2. Solids at room temperature
3. Extremely soluble in water

Fructose
•Sweetest sugar
•Found in fruits and honey
•Added to soft drinks and
deserts
Importance of monosaccharides
 Classification of carbohydrates

Three main groups : Monosaccharides | disaccharides|polysccharides

1. Monosaccharides
“Saccharide” – sakcharon- “sugar”
Simple sugars / single polyhydroxy aldehyde or ketone unit
Cannot be hydrolysed into smaller units
Aldehydes - aldoses or ketones- ketoses

Aldose Ketose
Classification of monosaccharides
C3 - Triose

C4 - Tetrose

C5 - Pentose

C6 - Hexose
Hexoses have different chemical composition

Glucose Fructose Galactose

Structure of glucose can be represented in three ways

Straight Haworth Chair form

chain form projection
Isomerism  Identical molecular formula but different
structure
Structural isomerism
Stereoisomerism.

Structural isomerism
Same formula but different structure- eg. glucose & fructose
6 CH2OH
HOCH2 O CH2OH
H H
5
O
4 1
OH H
H HO OH
OH 3 2 OH H

H OH
OH H
Glucose (C6H12O6) Fructose (C6H12O6)
 Stereoisomerism
Same molecular formula & structure but different spatial
arrangement of atoms
The presence of asymmetric carbon atoms allow this.
Asymmetric C atom is a C atom with 4 different groups
attached to it

Asymmetric C atom
CHO CHO
l l
H – C – OH HO – C – H
l l
The spatial arrangement
CH2OH of – OH is different.
CH2OH
In one it is on the right,
Glyceraldehyde On the other it is on the
(A triose) left.
 Isomerism of monosaccharides

 Same chemical formula but have different structures

Steroisomers : monosaccharides with asymmetric carbon atoms

have pair of structures that are mirror images
 Isomerism of monosaccharides
 Orientation of the - H and – OH groups around the carbon atom
present adjacent to the carbon atom of terminal primary alcohol
group
Right –D Left - L

 Most of the monosaccharides in mammals - D configuration

 Asymmetric C atom – rotates a beam of plane of
polarized light
 D and L : identical in all chemical and physical properties
except the direction they rotate the plane of polarized
light (optical isomerism / enatiomers).

Right - dextrorotatory (+) Left - levorotatory (-)

 Monosaccharides form epimers

 Very closely related sugars / differ in configuration of

a single carbon atom other than the anomeric
carbon (carbonyl carbon)
 Epimers of glucose - mannose and galactose
Hemiacetal & hemiketal formation

H H

C O + R' OH R' O C OH

R R
aldehyde alcohol hemiacetal

R R

C O + "R OH "R O C OH

R' R'
ketone alcohol hemiketal
 Glucose forms Cyclic Structures
 In aqueous solutions glucose exists in non reactive, inert cyclic
conformation > 99.99 / inertness - blood glucose
 The aldehyde/keto group reacts with an alcohol group on the
same sugar

The carbon atom which is involved in hemiacetal or acetal formation -

Anomeric Carbon
 Hexoses form Cyclic Structures

5- membered 6- membered
furanose pyranose

D- glucofuranose D- glucose D- glucopyranose

D- fructofuranose D- fructose D- fructopyranose

 Cyclization produces anomers
Cyclization of glucose produces a new asymmetric center at C1 called
anomeric C (former carbonyl C)

Isomeric forms that differ only in their configuration at

hemiacetal/hemiketal/anomeric c atom : anomers
α: OH below the ring (α-D-glucopyranose)
 β : OH above the ring (β -D-glucopyranose)
 Mutarotation

36% trace 64%

Chemical properties of monosaccharides
Heating with strong mineral acids (H2SO4, HCL) results in
the loss of water from the sugar forming a
furfural derivative

The furfural can condense with a napthol, thymol, resorcinol

to give coloured cpds. This is the basis of:

• Molisch’s test
• Seliwanoff’s test
• Bial’s
• Tollens – phloroglucinol – HCL test
 In dilute alkaline medium, both aldoses and ketoses
form enediols, which are reducing. This conversion
is dependent on the availability of a “FREE”
aldehyde or ketone group

This is the basis of Benedict’s and Fehling’s test

1 1 H
H – C – OH
H – C =O ll 1l
l H – C – OH
C – OH
H – C – OH l
2 l
l 2C=O
H – C – OH
H – C – OH l
l
l H – C – OH
H – C – OH
H – C – OH l
l
l H – C – OH
H –5 C – OH
H – C – OH l 5l
5 H – C – OH
l H – C – OH
H – C – OH 6 l
l 6
6l H – C – OH
H
H l
H

Aldose
Enediol Ketose
 Oxidation of Monosaccharides
 Monosaccharides oxidized by mild oxidizing agents - Cu2+
(alkaline CuSO4 - Benedict’s reagent) to form a red-orange
precipitate of copper(I) oxide (Cu2O).
 Carbonyl carbon oxidized to a carboxylic group.
 Sugars that undergo this reaction are called reducing
sugars.
 Sugar acids
Oxidation of Ald. Carbon / hydroxyl carbon or both.

Glucose is oxidized by hypobromous acid (HOBr) to

gluconic acid , glucosaccharic acid & glucuronic acid
Aldhyde
1
O
H – C =O O H–C=O
ll
l ll l
1 C – OH
H – C – OH C – OH H – C – OH
l
l l l
H – C – OH
H – C – OH H – C – OH H – C – OH
l
l l l
H – C – OH
H – C – OH H – C – OH H – C – OH
l
l l l
H – C – OH
H – C – OH H – C – OH H – C – OH
5 l
l l l
H – C – OH
H – C – OH H – C – OH C – OH
5l
6l l
H – C – OH ll
H C – OH O
6l
ll
1ry Alcohol. H
O

Glucose Gluconic acid Glucosaccharic acid Glucuronic acid

 Sugar Alcohols
Reduction of the carbonyl carbon produce polyhydroxy alcohols
Glucose Sorbitol

Mannose Mannitol

Fructose Sorbitol

Mannitol
1CH2OH
1CH2OH l 1 CH2OH
l l
2C=O
H – C – OH HO – C – H
2l l
l 2
H – C – OH
H – C – OH H – C – OH
l
l Reduction Reduction l
H – C – OH
H – C – OH H – C – OH
l
l 5 l
5 H – C – OH 5
H – C – OH H – C – OH
l
l l
6CH2OH
6CH2OH 6 CH2OH

Sorbitol Fructose Mannitol

 Glycosides formation
A condensation reaction between a – OH group of a
monosaccharide or monosaccharide residues and a second
compound that may or may not be a another monosaccharides.

1. If the second group is a hydroxyl an O-glycosidic bond is formed.

2. If the second group is an amine, and N-glycosidic bond is formed.
 Ester formation

 The primary or secondary alcohol groups in the sugar

molecules form esters with acids.
 The most important esters intermediatory metabolites in
carbohydrate metabolism.
 Amino sugars (Hexosamines)
– OH group replaced by an amino group-amino sugars.
eg: D – glucosamine, D – galactosamine , D – mannosamine

CH2OH CH2OH

H O H H O H
H H
OH H OH H
OH OH OH O OH
H NH2 H N C CH3
H
-D-glucosamine -D-N-acetylglucosamine
 Medical importance of monosaccharide

i. In therapy
 Glucose (dextrose) is used for intravenous feeding.
 Dextrose (25% or 50%) can be injected intravenously

ii. In diagnosis
metabolic disturbances can be detected by estimation of
urinary and blood levels of several sugars
Glucose - diabetics
Galactose - galactosaemia
Fructose - fructose intolerance
 Classification of carbohydrates

2.Disaccharides : Two monosaccharide units

Sucrose = Glucose + fructose

Maltose = Glucose + Glucose

Lactose = Glucose + Galactose

 Classification of carbohydrates

3. Oligosaccharides : 3-10 monosaccharide units

The monomers of a disaccharide / polysaccharide are
linked by “glycosidic bonds”

When the bonding is through an oxygen atom,

The glycosidic bond is called a

“O” glycosidic bond.

6 CH
6 CH
2OH 2OH

H H H
5 H 5
O O
4 1 4 1
H OH H
OH
OH O 3 2 OH
3 2

OH H OH
H
Glucose
Glucose
 Different types of glycosidic linkages

Three naturally occurring glycosidic linkages:

• 1-4’ link: Anomeric carbon - oxygen on C4 of second sugar.

• 1-6’ link: Anomeric carbon - oxygen on C6 of second sugar.
Reducing sugars

• 1-1,2’ link: Anomeric carbons of the two sugars are bonded.

Non-reducing sugars
 Maltose
Consists of 2 glucose units in α (1-4) glycosidic bond.
The anomeric C of one glucose is free. Hence it
has reducing properties.

6 CH
6 CH
2OH 2OH

H H H
5 H 5
O O
4 1 4 1
H OH H
OH
OH O 3 2 OH
3 2

OH H OH
H

a OH (below ring) of anomeric carbon associated with linkage

2 glucose units joined by “O-α (1-4)-glycosidic” bonds. This is maltose

 Lactose
The anomeric carbon of the bond comes from galactose.

The anomeric carbon of glucose is free  give reducing

properties.

OH on anomeric C is above ring (β), hence β (1-4)

6 CH
2OH 6 CH
2OH
H H
5 5 H
O O
4 1 4
OH H O H 1
OH
OH 3 2 H 3 2 OH

H OH OH
H

Galactose Glucose

Lactose  b (1-4) link

 Sucrose
with the α (1-2) link

No potential aldehyde or keto group. Hence non reducing

6 CH 1
2OH O H
HOCH2
H H
5
O 2 5
4 1
OH H
O H HO
OH 3 2 CH2OH
6
4
H OH

OH H

Glucose Fructose
α (1-6 ) glycosidic linkage
 Monosaccharides make polysaccharides

Polymerization of several hundred simple sugar units.

Also called glycans
Differ in the length of chains / the degree of branching.

Homopolysaccharides
Contain only a single type of monomeric unit (eg. starch,
amylose, amylopectin, cellulose, dextrins, glycogen, chitin).

Heteropolysaccharides
 Contain two or more different kinds of monomeric units. (eg.
glycoproteins, glycolipids).
 Polysaccharides

Storage Structural
Starch and Glycogen Cellulose, hemicellulose
 Starch-composition

Plants store sugar as starch / made of amylose (15 – 20%) and

amylopectin (80 – 85%).
Amylose
 A glucose polymer with α(14) linkages.
Soluble in boiling water.
Unbranched polymer , 200 – 2000 glucose units
Straight line / helix.
Blue colour formed with iodine : due to the complex formed
by iodine arranging themselves in the helix of amylose

Glycemic index of a starchy food is a measure of its digestibility

 Starch-composition
Amylopectin
 A glucose polymer with mainly α(14) linkages, but it also has
branches formed by α(16) linkages.
 The length of linear units in amylopectin is only 25.
 α(1->4) linkage (25) to α(1->6) linkage.
 The branches produce a compact structure & provide multiple
chain ends
CH2OH CH2OH
H O H H O H amylopectin
H H
OH H OH H 1
O
OH
O
H OH H OH

CH2OH CH2OH 6 CH2 CH2OH CH2OH

H O H H O H H 5 O H H O H H O H
H H H H H
OH H OH H OH H 1 4 OH H OH H
4 O O
O O OH
OH 2
3
H OH H OH H OH H OH H OH
 Glycogen
 Glucose storage polymer in animals
 Similar in structure to amylopectin. Both α(1→4) glycosidic
linkages and α(1→6) branch points.
 Highly branched : for every 8 to 12 glucose units.
 Insoluble /contribute little to the osmolarity of cytosol
 The highly branched structure permits rapid glucose release
from glycogen stores, e.g., in muscle during exercise.
 Red/brown colour - iodine
CH2OH CH2OH
H O O
glycogen
H H H
H H
OH H OH H 1
O
OH
O
H OH H OH

CH2OH CH2OH 6 CH2 CH2OH CH2OH

H O H H O H H 5 O H H O H H O H
H H H H H
OH H OH H OH H 1 4 OH H OH H
4 O O
O O OH
OH 2
3
H OH H OH H OH H OH H OH
 Cellulose

 A major constituent of plant cell walls, consists of long linear/

unbranched chains of  - D – glucopyronose units linked by
  (1 4) bonds, strengthened by cross linked hydrogen
bonds
CH2OH 6CH OH CH2OH CH2OH CH2OH
2
O 5 O O H O H O OH
H H H
H H H H H
OH H 1 O 4 OH H 1 O OH H O OH H O OH H
OH H H H
H 2 H
3
H OH H OH H OH H OH H OH

 Every other glucose is flipped over, due to β linkages.

 Promotes intra-chain and inter-chain H-bonds and van der Waals
interactions, cause cellulose chains to be straight & rigid, and pack
with a crystalline arrangement in thick bundles - microfibrils.
 Microfibrils are very strong.
 Role - to impart strength and rigidity to plant cell walls, can
withstand high hydrostatic pressure gradients. Osmotic
swelling - prevented.
 Cannot be digested by many mammals - absence of a
hydrolase that attacks the  - linkages.

 An important sources of “bulk” in the diet.

 Stimulates intestine to contract / propel the food undergoing
digestion in expulsion of feces.
Homopolysaccharides - single monomers
Chitin

 Linear polysaccharide
 Structural polysaccharide of invertebrates.
 Exoskeletons of crustaceans and insects.
 N – acetyl – D – glucosamine units joined by  (1 4)
glycosidic bonds
Glycoproteins
 Glycoproteins
 Heteropolysaccharides
 Sugars are covalently attached to peptide back bone via
amino sugars (N-acetylglucosamine and N-
acetylgalactosamine)
 Carbohydrate chain is relatively short , often branched
 May/may not be negatively charged
 Almost all the plasma proteins of humans, except albumin are
glycoproteins.
 Glycoprotein- structure
two types of glycopeptide bonds. 1. N – Glycosyl linkage

2. O - Glycosyl linkage
 Glycoprotein plays a major role in the body
Structural molecules
Lubricants /protective agents
Transport molecules for
Vitamins, Lipids, Minerals
Immunologic molecules
Hormones
Enzymes
Cell attachment
Recognition sites
Membrane glycoproteins
Collagen, elastin,
fibrins, bone, matrix
Mucins, mucous secretions,
snake venous toxins
Transferrin
Immunoglobulins,
histocompatibility antigens,
Chorionic gonadotrophin,
Thyrotrophin
Proteases, Nucleases
Cell – cell
Virus – cell/ cell-cell
Bacterium – cell, Hormone
receptors
Glycoproteins - mucins
 Glycoproteins - mucins
O – linked glycoproteins
in the secretion of mucous membrane / lubricative and protective
properties.
Multiple COO- group of N – acetylneuramic acid / negatively
charged / repel each other and prevent folding
Give an extended rod like conformation / forms a viscoelastic gel
Other sugars sulphated / similar properties.

Function
1. Protect the mucous membranes of the respiratory gastro-
intestinal and other tracts by acting as a protective barrier on
the epithelial surface
2. provide lubrication.
3. The high density of oligosaccharide chains block the approach
of proteases
 Glycoproteins - Collagen

 Protein backbone - monosaccharides and disaccharides

Covalently attached to hydroxylysine in glycosidic linkage.
 Only protein contain glucose as the sugar.
 Carbohydrate content of collagen varies according to the
type and distributions.
 Glycoproteins in human blood cells
Human blood group antigens

Many plasma membrane

proteins - glycoproteins.
Eg: Glycophorin, the human
red cell membrane.
Contains - 60% carbohydrate.

 Carbohydrate chains facing out

 Blood group recognition sites.
 Specificity is determined by the nature
of the sugar residues in major blood
groups .
 Glycoproteins determines the blood type

Four main blood groups.

A, B, AB and O- depending
on the carbohydrate residues.
Face outside the cell
membrane.
Antigens differ from one
another
only in the sugar residues in
peripheral portion
 Glycoproteins in bacterial cell wall

Bacterial cell wall polysaccharide

 bacterial cell wall - long parallel polysaccharide chains cross linked
to each other at intervals by short polypeptide chains.
 Polysaccharide chains - alternating monosaccharide units; N–
acetyl glucosamine, N–acetyl muramic acid. linked by (1 4)
linkages.
 Attached to each N– acetyl muramic acid unit
 Lectins

Carbohydrate binding proteins /

bind one or more specific sugars.
Tools for probing the surface of
cells/ lectins recognize specific
sugars exposed on the surface
membrane of cells.
The binding of lectin to specific
sugars - agglutinating of the cells.
Agglutinate cancer cells/
Showing that cancerous
transformation involve alteration
of the cell surface sugars
 Role of carbohydrates in glycoproteins

1. Modulate physiochemical properties (solubility, viscosity

charge and denaturation)
Oligosaccharides are hydrophilic and increases solubility of proteins
Glycoproteins : high stability to heat, detergents, acids and bases.
 Role of carbohydrates in glycoproteins

2.Protein folding conformation and stabilization of biological

membranes

 Carbohydrates are needed for folding and acquisition of the

correct conformation of certain proteins and they also participate
in subunit interactions.
 The presence of carbohydrate is not always essential for the
particular function of glycoprotein in which it occurs.
 The carbohydrate of transmembrane, glycoproteins may help to
orient and anchor these molecules in the lipid bilayer.
 The carbohydrate of glycoproteins, protect these molecules
against proteolysis from inside and outside the cell.
 Role of carbohydrates in glycoproteins

3. Biological recognition
immunological determination structures of blood groups, A, B,
and AB and O
act as acceptors for lectins / involved in cell adhesion.

4. Involved in biologic activity eg: hormone actions

5. Target proteins to specific sub cellular locations

 Proteoglycans

High MW chains linked covalently to a “core

protein” containing 95% carbohydrates

Component of extra cellular matrix

 Proteoglycans
Sugar chain is long and unbranched with repeating disaccharides
 Repeating disaccharides: glycosaminoglycans
 Glycosaminoglycans are heteropolysaccharides containing
amino sugars (hexosamine) and uronic acids.
 Glycosaminoglycans covalently linked to proteins
 Proteoglycans structural features

High MW chains linked covalently to a protein core

3 types of proteoglycan polysaccharide - polypeptide linkages

1. O – glycosidic bond / Xyl - Ser

2. O – glycosidic bond / GalNAC -Ser (Thr)
3. N – glycosylamine bond / GlcNAC - Asn.

Types of polysaccharides distinguished by

a. monosaccharides composition.
b. glycosidic linkage.
c. amount and location of their sulfate substituent.
 Glycosaminoglycans

Six classes

I. Hyaluronic acid
II. Chondroitin sulfate
III. Keratan sulfate I and II.
IV. Heparin
V. heparan sulfate
VI. Dermatan sulfate.
 Hyaluronic acid
Bacteria and animal organisms /
tissues
Unsulfated
Synovial fluid of joints
Clear /Highly viscous solution
Provide lubrication

vitreous body of the eye

Jelly like consistency to eye /
glassy appearance

In cartilage and tendons

Tensile strength and elasticity
Amino group of glucosamine is
acetylated : eliminate the
positive charge
Contribute to compressibility
 Chondroitin sulfate
Cont….

 Prominent component of
cartilage
 To maintain the neuronal shape

 Associate tightly with

hyaluronic acid with the aid of
“link protein” to generate very
large aggregates in connective
tissue

 GlaNAC carries a sulfate substituent in the 4 – or 6 – position

 One sulfate substituent per disaccharide unit

 Chondroitin sulfate
 bind electrostatically each other and structural Cont….
components of matrix, collagen and elastin.

 Chondritin sulphate binds to collagen and forms a cross-

linked mesh giving strength and resilience to ECM

 Holds the cells together and provide a porous pathway / act

as a molecular sieve : for diffusion of nutrients and oxygen
to individual cells
 Some are polyanions and bind to polycatios which attracts
water into ECM provide turgor
 The structure and hydration of the ECM provide rigidity,
combined with flexibility and compressibility, enabling tissue to
withstand torsion and shock.
 Keratan sulfate

Keratan sulfate I – cornea

keratan sulfate II - present along with

chondroitin sulfate, attached to
hyaluronic acid in loose connective
tissue.

In cartilage, bone and horny structures

 Heparin
 An important anticoagulant in blood
 Stored in granules of mast cells / in intracellular
 Most GlcN residues N – sulfated, few acetylated
 90% of the uronic acid residues - IdUA
 IdUA frequently sulfated
 Protein molecule of heparin proteoglycan is unique, consisting
exclusively serine and glycine residues
 Heparin- functions

Interactions with plasma proteins

 synthesized and stored in mast cells, always in close

proximity to blood vessels.
 high negative charge density, interacts, strongly with
several plasma components.
 bind to blood clotting factors and to lipoprotein lipase
present in capillary walls and cause release of triglyceride
degrading enzyme into circulation.
 Heparan sulfate
Associated with plasma membranes .
More acetylated of the GlcNAc residue, fewer N – sulfates.
Act as receptors in cell growth and cell to cell
communication
Some cell surface heparan sulfate glycosaminoglycans -
covalently linked to core proteins spanning the membrane
 Dermatan sulfate
 Widely distributed in skin, blood vessels, tendon and heart valves.
 To maintain the overall shape of the eye
 Resembles both chondroitin sulfates and heparin sulfate.
 Formation - as in heparin and heapran sulfate.
 Proteoglycans - functions

 Provide the ground/packing substance of connective tissues

 Ions draw a large quantities of water and occupy space causing

swelling and stiffening the matrix

 Produce a gel-like matrix that forms the body’s ground

substance

 Containing a large number of sulfate and carboxylate groups :

gives a high density of negative charge

 Induces a repulsion, forms a rod like helix / keep the carboxylic

groups on alternative sides
 Proteoglycans - functions

 extended rod form in a solution and surrounded by a shell of

water molecules

 When compressed – water “squeezed out” and occupy a

smaller volume and when compression released spring back to
original volume due to the repulsion of the negative charges

 Provides resilience, cushioning the impact between bones