carbohydrates

Carbohydrates
Carbohydrates are the most abundant organic molecules in nature.
Hydrates of carbon
Carbohydrates are defined as polyhydroxyaldehydes or ketones or
compounds which produce them on hydrolysis.
Composed of carbon, hydrogen and oxygen
General molecular formula Cn (H2O)n
Some carbohydrates contain Sulphur, Nitrogen or Phosphorus

Functions of Carbohydrates
Main sources of ENERGY in body (4kcal/g)
RBCs and Brain cells have an absolute requirement of carbohydrates.
Storage form of energy (starch and glycogen)
Excess carbohydrate is converted to fat.
Glycoproteins and glycolipids are components of cell membranes and
receptors.
Structural basis of many organisms.e.g. Cellulose in plants, exoskeleton of
insects, cell wall of microbes, mucopolysaccharides and ground substance in
higher organisms.

Classification of Carbohydrates
Carbohydrates

Monosaccharides
1 sugar unit

e.g.Glucose,
fructose etc

Disaccharides
2 sugar units

e.g.Sucrose

Oligosaccharides
3-9 units

Polysaccharides
>10

e.g. Maltotriose

Homoglycans

e.g. starch,
glycogen

Heteroglycans
e.g. GAGs or
glycosaminoglycans

Monosaccharides
Molecules having only one actual or potential sugar group
No. of
carbon
3
4
5

Generic
name

Aldoses

Ketoses

Trioses

Aldotriose e.g.
glyceraldehyde

Ketotriose e.g.
Dihydroxyacetone

Tetroses

Aldotetrose e.g.
Erythrose

Ketotetrose e.g.
Erythrulose

Pentoses

Aldopentoses e.g
Arabinose, Xylose,
Ribose

Ketopentoses e.g.
Xylulose, Ribulose

Hexoses

Aldohexose e.g.
Glucose, Galactose,
Mannose

Ketohexose e.g.
Fructose

Aldoheptose:
Glucoheptose

Ketoheptose e.g
Sedoheptulose

Heptoses

Pentoses of Physiological importance

Hexoses of Physiological Importance

Stereoisomers
Compounds having same structural formula, but differing in spatial
configuration are known as stereoisomers.
Asymmetric carbon:
Four different groups are attached to the same carbon.
The reference molecule is glyceraldehyde.
All monosaccharides can be considered as molecules derived from
glyceraldehyde by successive addition of carbon atoms.

Penultimate
Carbon

Stereoisomers

D and L Isomers of glucose

D and L Isomers are mirror images of each other.
The spatial orientation of H & OH groups on the C-atom (C5 for glucose),
adjacent to the terminal primary alcohol carbon determines whether the sugar
is D or L Isomer.
If the OH group is on the right side, the sugar is of D-Isomer.
If the OH group is on the left side, the sugar is of L-Isomer.
Mammalian tissues have D- sugars.

Aldoses

Ketoses

Optical activity
Optical activity is a characteristic feature of compounds with asymmetric carbon atom.
When a beam of polarized light is passes through a solution of an optical isomer, it will be
rotated either to the right or left.
Depending on the rotation, molecules are called dextrorotatory (+) or levorotatory (-).
Racemic mixture: If d & l isomers are present in equal concentration, it is known as racemic
mixture.
NOTE: Racemic mixture does not exhibit any optical activity.

Epimers
If two monosaccharides differ from each other in their configuration around a single
specific carbon atom, they are referred as epimers to each other.
Glucose & galactose are C4-epimers
Glucose & mannose are C2-epimers
Inter-conversion of epimers is known as epimerization, epimerases catalyzes this reaction.

Enantiomers
Enantiomers are a special type of stereoisomers, that are mirror images of each
other.
Majority of sugars in higher animals are of D-type.

Diastereoisomers
The term diastereomers is used to represent the stereoisomers that are not mirror images of
one another.
Configurational changes with regard to C2 , C3 and C4 will produce eight different
monosaccharides.

Total D + L forms = 16 isomers of glucose

Physical Properties
Reference Carbon atom of Sugars: Penultimate carbon atom is the reference carbon atom for naming sugars.
All monosaccharides can be considered as molecules derived from glyceraldehyde by
successive addition of C units.

Penultimate
carbon

Anomerism

Anomers have same composition but differ in the orientation of groups around anomeric carbon
atom, Anomeric carbon being the functional group of the carbohydrate .
Anomeric carbon is a carbonyl carbon atom, e.g. 1st carbon atom in glucose is anomeric carbon
atom.
Carbonyl carbon atom becomes asymetric because of ring structures of monosaccharides in
solution thus anomers are encountered in cyclic structures of monosaccaharides.
The alpha & beta cyclic forms of D-glucose are known as anomers.
They differ from each other in the configuration only around C1 known as anomeric carbon.
The hemiacetal (or carbonyl) carbon atom is called the anomeric carbon.
In case of alpha anomer, the OH group held by anomeric carbon is on the opposite side of the
group CH2OH of sugar ring.

Mutarotation:
When D-glucose is crystallized at room temperature and a fresh solution is
prepared, its specific rotation of polarized light is 112o; but after 12- 18 hrs it
changes to +52.5 o
This change in rotation with time is called as mutarotation.
Glucose has two anomers and .
Traces of linear forms,
intermediate forms

Stereochemistry in carbohydrates
same chemical/physical
property

Enantiomers
Same connectivity
Have chiral carbon
superimposable
Mirror image each
other

Diastereomers
Same connectivity
Have chiral
carbon
Non
superimposable
No Mirror image

chiral centre

Mirror image

Not Mirror image

diff chemical/physical property

diff configuration at one or more
of equivalent stereocenter
mirror image
diff configuration
not mirror image
same configuration
2 chiral centre22= 4 stereoisomer
3 chiral centre 23 = 8 stereoisomer
2n

n = chiral centre

Glucose Isomers
Enantiomer/mirror image

Natural occur sugar D form

Glucose 4 stereocenter
C5 chiral center further from C1
OH on right
- D form
All chiral center
diff configuration

Mirror image

*
*
*
*

D glucose

L - glucose

OH at C1 bottom ring
glucose

equilibrium bet straight chain ring form

OH at C1 top ring
glucose
glucose

glucose

Stereochemistry in carbohydrates
same chemical/physical property

Enantiomers
Same connectivity
Have chiral carbon
superimposable
Mirror image each
other

Diastereomers
Same connectivity
Have chiral carbon
Non
superimposable
No Mirror image

chiral centre

Mirror image

Not Mirror image

diff chemical/physical property

diff configuration at one or more
of equivalent stereocenter
mirror image
diff configuration
not mirror image
same configuration
2 chiral centre22= 4 stereoisomer
3 chiral centre 23 = 8 stereoisomer
2n

n = chiral centre

Fructose Isomers
Enantiomer/mirror image

Natural occur sugar D form

Fructose 3 stereocenter
C5 chiral center further from C1
OH on right
- D form
All chiral center
diff configuration

Mirror image

*
equilibrium bet straight chain ring form
D fructose

L - fructose

OH at C2 bottom ring
fructose

OH at C2 top ring
fructose
fructose

fructose

Stereochemistry in carbohydrates
Glucose Isomers
Enantiomer/mirror image

Natural occur sugar D form

Glucose 4 stereocenter
C5 chiral center
OH on right
- D form

*
*
*

All chiral center

diff configuration

Mirror image

D glucose

equilibrium bet straight chain ring form

L - glucose

Starch

Cellulose

(1-4 glycosidic link)

glucose

glucose

glucose

All OH gp below

Starch/glycogen - glucose link together (1-4 glycosidic link)

Human have amylase recognise glucose - can digest starch

(1-4 glycosidic link)

glucose

glucose

glucose

glucose

OH gp alternate
Cellulose - glucose link together (1-4 glycosidic link)
Cow have cellulase recognise glucose can digest cellulose
Cellulose fibre to human strong long chain - H 2 bond bet chain

Interrelationship of Carbohydrates with Proteins and lipids

Glycoproteins and glycolipids are formed when sugars combine, respectively, with proteins
and lipids. Biologically these are important compounds as they are an integral part of cell
membranes.
Glycoproteins are also often important integral membrane proteins, where they play a role
in cellcell interactions.
Glycolipids are lipids with a carbohydrate attached by a glycosidic bond. Their role is to
serve as markers for cellular recognition and also to provide energy.
Biological membranes are composed of proteins, lipids and carbohydrates. The
carbohydrates in the membrane are covalently bonded to proteins (glycoproteins) or with
lipids (glycolipids).

Cell surface carbohydrates and blood groupings

Small polysaccharide chains, covalently bonded by glycosidic links to hydroxyl groups on
proteins (glycoproteins), act as biochemical markers (i.e. antigenic determinants) on cell
surfaces.
The membrane of the red blood cells (RBCs) contains glycoproteins/glycolipids, and the
type of sugar that combines with these proteins/lipids varies from person to person. This
gives rise to different blood groups (A, B, AB and O).
Other examples
Glycoproteins
One example of glycoproteins found in the body is mucins, which are secreted in the
mucus of the respiratory and digestive tracts. The sugars when attached to mucins give
them considerable water-holding capacity and also make them resistant to proteolysis by
digestive enzymes.
Glycoproteins are important for white blood cell recognition, especially in mammals.
molecules such as antibodies (immunoglobulins), which interact directly with antigens.
molecules of the major histocompatibility complex (or MHC), which are expressed on the
surface of cells and interact with T cells as part of the adaptive immune response.

 Glycolipids
Cellcell Interactions
The sugar moiety of the glycolipid will bind to a specific complementary carbohydrate
or lectin, type of cell-surface protein, of a neighboring cell. The interaction of these cell
surface markers initiates cellular responses that contribute to activities such as cell recognition,
regulation, growth, and apoptosis
Immune Responses
An example of how glycolipids function within the body is the interaction between leukocytes
and endothelial cells during inflammation. Selectins on the surface of leukocytes and
endothelial cells will bind to the carbohydrates attached to glycolipids to initiate the immune
response. This binding allows for leukocytes to leave circulation and congregate near the site
of inflammation. This is the initial binding mechanism, after which it is followed by
expression of integrins which form stronger bonds and allow leukocytes to migrate toward the
specific site of inflammation

Connection of Proteins and Carbohydrates in Glucose metabolism

Proteins are hydrolyzed by a variety of enzymes in cells.
Most of the time, the amino acids are recycled into the synthesis of new proteins. If there are
excess amino acids, or if the body is in a state of starvation, some amino acids will be
shunted into the pathways of glucose catabolism.
Each amino acid must have its amino group removed prior to entry into these pathways. The
amino group is converted into ammonia.
In mammals, the liver synthesizes urea from two ammonia molecules and a carbon dioxide
molecule. Thus, urea is the principal waste product in mammals produced from the nitrogen
originating in amino acids, and it leaves the body in urine.

Figure:The carbon skeletons of certain amino acids (indicated in boxes) derived from proteins can feed into the citric acid
cycle. (credit: modification of work by Mikael Hggstrm)

Connection of Lipids and Carbohydrates

The lipids that are connected to the glucose pathways are cholesterol and triglycerides.
Cholesterol is a lipid that contributes to cell membrane flexibility and is a precursor of steroid
hormones. The synthesis of cholesterol starts with acetyl groups and proceeds in only one
direction. The process cannot be reversed.
Triglycerides are a form of long-term energy storage in animals. Triglycerides are made of
glycerol and three fatty acids. Animals can make most of the fatty acids they need.
Triglycerides can be both made and broken down through parts of the glucose catabolism
pathways.
Fatty acids are catabolized in a process called beta-oxidation that takes place in the matrix of
the mitochondria and converts their fatty acid chains into two carbon units of acetyl groups.
The acetyl groups are picked up by CoA to form acetyl CoA that proceeds into the citric acid
cycle.

Figure:Glycogen from the liver and muscles, hydrolyzed into glucose-1-phosphate, together with fats and proteins, can
feed into the catabolic pathways for carbohydrates.

Sugar alcohols
Sugar alcohols (also called polyhydric alcohols, polyalcohols, alditols or glycitols)
are organic compounds, typically derived from sugars, that comprise a class of polyols.
Contrary to what the name may suggest, a sugar alcohol is not a sugar nor an alcoholic
beverage. They are white, water-soluble solids that can occur naturally or be produced
industrially from sugars.
They are used widely in the food industry as thickeners and sweeteners.
In commercial foodstuffs, sugar alcohols are commonly used in place of table sugar
(sucrose), often in combination with high intensity artificial sweeteners to counter the low
sweetness.
Xylitol is perhaps the most popular sugar alcohol due to its similarity to sucrose in visual
appearance and sweetness.

Structure
Sugar alcohols have the general formula HOCH2(CHOH)nCH2OH. In contrast, sugars have
two fewer hydrogen atoms, for example HOCH2(CHOH)nCHO or
HOCH2(CHOH)n1C(O)CH2OH
Common sugar alcohols
Glycerol (3-carbon)
Erythritol (4-carbon
Xylitol (5-carbon)
Mannitol (6-carbon)
Erythritol
Sorbitol (6-carbon)
Inositol (6-carbon; a cyclic sugar alcohol)
Volemitol (7-carbon)
Isomalt (12-carbon)
Polyglycitol

Sucrose
Sucrose is a disaccharide that is composed of a unit of glucose (acetal form) and a unit of
fructose (ketal form) linked through C-1 of glucose and C-2 of fructose, i.e. a 1,20 link.
In sucrose, neither glucose nor fructose can exist in open chain form because of the
formation of acetal and ketal as shown below. As a result, sucrose is not a reducing sugar,
and does now exhibit mutarotation.
The specific rotation [a]D of sucrose is 66. Hydrolysis of sucrose yields glucose and
fructose with specific rotations [a]D52.5 and 92, respectively, and makes the resulting
mixture levorotatory. This phenomenon of sucrose is called the inversion of sucrose, and
the resulting mixture is known as invert sugar, which is the main component of honey, and
is sweeter than sucrose itself.

Starch
Starch, an essential component of our diet, is a high molecular weight polymer of glucose
where the monosaccharide (glucose) units are linked mainly by 1,4-a-glycoside bonds, similar
to maltose.
Plants are the main source of starch. Starch is obtained from wheat (Triticum sativum), rice
(Oryza sativa) and maize (Zea mays), all from the plant family Gramineae. Potato (Solanum
tuberosum; family Solanaceae) and maranta (Maranta arundinacea; family Marantaceae) are
also good sources of starch.
Starch consists of two main components: amylose (insoluble in cold water) and amylopectin
(soluble in cold water). Amylose, which accounts for about 20 per cent by weight of starch,
has an average molecular weight of over 106.
It is a polymer of glucopyranose units linked together through a 1,4-linkages in a linear chain.
Hydrolysis of amylose produces maltose.

Applications
The pharmaceutical and cosmetic uses of starch include its use as dusting powder, binder,
dispersing agent, thickening agent, coating agent and diluent.
Starch soaks up secretions and helps to render injured parts less liable to bacterial
infections.
As a dusting powder for application to chafings and excoriations, it is used either alone or
mixed with zinc oxide, boric acid and other similar substances.
Boiled with water it may be employed as an emollient for the skin.
Starch is the best antidote for poisoning by iodine

Cellulose
Cellulose, the most abundant natural organic polymer, consists of several thousands of Dglucose units linked by 1,4-b-glycoside bonds.
Cellulose has a linear chain structure. Different cellulose molecules can then interact to form a
large aggregate structure held together by hydrogen bonds.
On hydrolysis, cellulose produces cellobiose, and finally glucose.
Nature uses cellulose mainly as a structural material to provide plants with strength and
rigidity.
Human digestive enzymes contain a-glucosidase,but not b-glucosidase. Therefore, human
digestive enzymes cannot hydrolyze b-glycosidic links between glucose units.
In human beings, starch (but not cellulose), is hydrolyzed enzymatically to produce glucose.
Therefore, cellulose does not have any dietary importance.

Applications
Although there is no food value in cellulose for humans, cellulose and its derivatives are
commercially important.
Cellulose is used as raw material for the manufacture of cellulose acetate, known
commercially as acetate rayon, and cellulose nitrate, known as guncotton.
Commercially important fibres, e.g. cotton and flax, consist almost completely of cellulose.
Water soluble, high viscosity grade cellulose ether compositions are useful for the reduction
of serum lipid levels, particularly total serum cholesterol, serum triglycerides and low
density lipoprotein (LDL) levels, and/or attenuate the rise of blood glucose levels.
Cellulose derivatives, e.g. hydroxyethylcellulose, are used in the formulation of sustained
release tablets and suspensions.
Natrosol (hydroxyethylcellulose) is a nonionic water-soluble polymer that is extensively
used as a thickener, protective colloid, binder, stabilizer and suspending agent, particularly
in applications where a nonionic material is desired.
Natrosol is also used in cosmetic preparations as a thickening agent for shampoos,
conditioners, liquid soaps and shaving creams.

Heparin
Heparin is an injectable blood thinner (anticoagulant).
It is used to treat and prevent deep vein
thrombosis and pulmonary embolism.
It is also used as part of the treatment of myocardial
infarction and unstable angina.
heparin is a polymer with a molecular weight ranging from
3 to 30 kDa
Heparin is a member of the glycosaminoglycan family
of carbohydrates (which includes the closely related
molecule heparan sulfate) and consists of a variably
sulfated repeating disaccharide unit.
The most common disaccharide unit is composed of a 2-Osulfated iduronic acid and 6-O-sulfated, N-sulfated
glucosamine, IdoA(2S)-GlcNS(6S).
This makes up 85% of heparins from beef lung and about
75% of those from porcine intestinal mucosa.

Low molecular weight heparins (LMWHs)

Low molecular weight heparins (LMWHs) are obtained through
various methods of chemical and enzymatic depolymerization from
clinical-grade unfractioned heparin.
LMWH may in principle be prepared by fractionation of UFH or by its
depolymerisation.
deaminative cleavage with nitrous acid or an organic nitrite
Chemical or enzymatic beta-elimination
Oxidative depolymerisation
As the method of depolymerization varies between products, each
LMWHs has an specific fingerprint in its chemical structure and an
own distinctive molecular weight profile.
Typically LMWHs have a mean molecular weight between 3000 and
7,000 Da.
Unlike unfractioned heparin, LMWH chains are too small to form a
ternary complex with the thrombin and the antithrombin.
Consequently, they exert its anticoagulant activity primarily through
inhibition of factor Xa.

LMWH

Average
molecular
weight

Bemiparin

3600

Nadroparin

4300

Reviparin

4400

Enoxaparin

4500

Parnaparin

5000

Certoparin

5400

Dalteparin

5000

Tinzaparin

6500

The advantages of LMWH over unfractionated heparin are:

1. Better bioavailability: this type of heparin does not bind to proteins or endothelial cells, nor
it is neutralized by plasma proteins. Therefore the entire dosage performs the anticoagulant
function.
2. More predictable dose-response: Monitoring or dose adjustment is not needed during its
administration.
3. Less frequent subcutaneous dosing: Its plasma half-life is longer than that of unfractionated
heparin, therefore it can be administered subcutaneously once or twice daily instead of
intravenous infusion of high dose heparin.
4. Other:
. Possibly a smaller risk of bleeding.
. Smaller risk of osteoporosis in long-term use.
. Smaller risk of heparin-induced thrombocytopenia, a potential side effect of heparin.
. The anticoagulant effects of heparin are typically reversible with protamine sulfate, while
protamine's effect on LMWH is limited.
. LMWH has less of an effect on thrombin compared to heparin, but about the same effect on
Factor Xa.

Medical uses of Heparin

In thearapeutic doses, it acts as an anticoagulant, preventing the formation of clots and
extension of existing clots within the blood.
While heparin does not break down clots that have already formed (unlike tissue
plasminogen activator), it allows the body's natural clot lysis mechanisms to work normally
to break down clots that have formed.
Heparin is generally used for anticoagulation for the following conditions:
Acute coronary syndrome,
Atrial fibrillation
Deep-vein thrombosis and pulmonary embolism
Cardiopulmonary bypass for heart surgery
ECMO circuit for extracorporeal life support
Hemofiltration
Indwelling central or peripheral venous catheters
Cryonics
Heparin and its low-molecular-weight derivatives (e.g., enoxaparin, dalteparin, tinzaparin)
are effective at preventing deep vein thromboses and pulmonary emboli.

Glycosides
Compounds that yield one or more sugars upon hydrolysis are known as glycosides.
A glycoside is composed of two moieties: sugar portion (glycone) and non-sugar portion
(aglycone or genin).
For example, the hydrolysis of salicin produces a glucose unit and salicyl alcohol.
Glycosides of many different aglycones are extensively found in the plant kingdom.
Many of these glycosides are formed from phenols, polyphenols, steroidal and terpenoidal
alcohols through glycosidic attachment to sugars.
Among the sugars found in natural glycosides, D-glucose is the most prevalent one, but Lrhamnose, D- and L-fructose and L-arabinose also occur quite frequently.
Of the pentoses, L-arabinose is more common than D-xylose and the sugars often occur as
oligosaccharides.
The sugar moiety of a glycoside can be joined to the aglycone in various ways, the most
common being via an oxygen atom (O-glycoside).
However, this bridging atom can also be a carbon (C-glycoside), a nitrogen (N-glycoside) or
a sulphur atom (S-glycoside).
By virtue of the aglycone and/or sugar, glycosides are extremely important pharmaceutically
and medicinally. For example, digitoxin, a cardiac glycoside

Classification

Based on sugar component

Glycosides that contain glucose are called
glucoside.
Similarly, when the sugars are fructose or
galactose, the glycosides are called fructoside or
galactoside, respectively
Based on aglycone
Glycosides can be classified on the basis of the
structural types of aglycone present in the
glycoside.
For example, in anthraquinone, flavonoid, iridoid,
lignan or steroid glycosides, the aglycones are
anthraquinone, flavonoid, iridoid, lignan or
steroid, respectively

Based on properties or functions

Glycosides that have soaplike properties are called
saponins.
Similarly, glycosides that liberate hydrocyanic acid
(HCN) on hydrolysis are known as cyanogenic
glycosides, and
glycosides that have an effect on heart muscle are
called cardiac glycosides.