Carbohydrate Structure and Function
Carbohydrate Structure and Function
Carbohydrate Structure and Function
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Functions
Primary source of energy (eg. glucose)
Energy storage (glycogen, starch)
Structural component of cell membrane & nervous tissue.
Structural component of many organisms: cell walls of
bacteria(Peptidoglycan), the exoskeleton of many insects and cell
wall of fungi(Chitin), plant cell wall(cellulose).
Can be attached to other macromolecules (glycoproteins and
glycolipids)
Other carbohydrate polymers
Lubricate skeletal joints/synovial fluid & in vitreous fluids.
Recognition & adhesion b/n cells: intercellular signaling
moieties when covalently-linked to cell surface glycoproteins.
Structural components of nucleic acids and blood groups
Metabolic precursors of all other biomolecules: proteins,
nucleotides , coenzymes, fatty acids.. 3
All of these functions are made possible by the characteristic
chemical features of carbohydrates, such as the:
• Existence of at least one & often two or more asymmetric
centers.
• Ability to exist either in linear or ring structures.
• Capacity to form polymeric structures via glycosidic bonds.
• Potential to form multiple hydrogen bonds with water or other
molecules in their environment.
Diseases are associated with abnormal carbohydrate
metabolism. Includes, Diabetes mellitus, Galactosemia, Lactose
intolerance, Glycogen storage diseases, etc.
No specific carbohydrates have been identified as dietary
requirements.
Carbohydrates can be synthesized from amino acids, and we can
convert one type of carbohydrate to another.
However, health problems are associated with the complete 4
aldose ketose
aldehyde
ketone
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Monosaccharides Nomenclature….
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Monosaccharides…
Examples of
Examples of Aldoses/ Monosaccharides Ketoses/Monosaccharides
containing aldehyde functional group containing ketone
functional group
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Important Monosaccharides
oD-glyceraldehyde and dihydroxyacetone are aldo- and keto-
trioses, respectively, that are intermediary compounds in
carbohydrate and lipid metabolism.
oD-Ribose is the most important pentose obtained from Nucleic
acids hydrolysis, component of RNA, DNA, ATP, GTP etc. and a
number of coenzymes. It is a reducing aldo-sugar synthesized in
the body from glucose.
oGlucose (or dextrose) is the grape and blood sugar. Glucose is
the building unit and end product of hydrolysis of starch, dextrin,
glycogen, sucrose, maltose and lactose. All monosaccharides
ingested may be converted into glucose in the body and all can be
synthesized from it.
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Glucose is the most important carbohydrate b/c:
The most abundant monosaccharide in nature
As glucose that the dietary carbohydrate is mainly absorbed into
the blood stream or into w/c it is converted in the liver
It is a major fuel of human tissues
It is converted to other carbohydrates having specific functions
such as; Glycogen(storage),Ribose(nucleic acids),Galactose
(lactose of milk & complexes with lipids & proteins).
Mannose is a subunit in glycoproteins and neuraminic acid. It is
obtained by hydrolysis of the plant mannosans and gums.
Galactose is a subunit of the milk sugar, lactose. It is also a
constituent of the structure of glycoproteins, glycolipids and
mucopolysaccharides.
Fructose- sweetest sugar. It is the main sugar in bee's honey and
fruits. It is obtained from inulin and sucrose hydrolysis. It is
called the semen sugar, since it is present in seminal fluid and
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H OH HO H
CH2OH CH2OH
D-Glyceraldehyde L-Glyceraldehyde
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Glyceraldehyde is considered as a reference sugar for other sugars.
C. Epimers- Carbohydrate isomers that differ in configuration
around only one specific carbon atom are defined as epimers of
each other. They differ in distribution of H and OH groups around
a single asymmetric carbon atom.
For example, glucose and galactose are epimers—their structures
differ only in the position of the -OH group at carbon 4.
D-Mannose and D-Galactose are not epimers)
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D. Geometric isomers: These are isomers that differ in distribution
of atoms or groups around the axis of a double bond in space,
e.g., cis-form of a compound that has groups on the same side of
the double bond and trans-form that has the groups on opposite
sides of the double bond.
Examples- cis-fumaric acid in which the two carboxylic groups
are present on one side and trans-fumaric acid in which these
groups are present on the opposite sides of the C=C bond.
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2. Optical property- is a characteristic feature of compounds with
asymmetric carbon
When a beam of plane- polarized light is passed through a
solution of an optical isomer, it will be rotated either to the
right when the sugar is dextrorotatory(d or +), such as
glucose, galactose and starch; or to the left when the sugar is
levorotatory (l or –), such as fructose and invert sugar.
Racemic mixture (+)-is a solution containing dextrorotatory=
levorotatory & is optically inactive.
All the monosaccharides except dihydroxyacetone contain at
least one asymmetric (chiral) carbon atom and hence
optically active.
Eg. The two optical isomers of glyceraldehydes containing one
asymmetric carbon atom are D-glyceraldehyde and L-
glyceraldehyde which are mirror images of each other
These optical isomers are called enantiomers.
In nature D-isomer is abundant and sugars present in the body
are all D-isomers. 17
Enantiomers
Enantiomers
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3. Cyclization of monosaccharides
Monosaccharides with five or more carbons exists
predominantly in a ring (cyclic) form in aqueous solution as
they are often more stable in as cyclic structures than they are
as open chains.
In cyclic monosaccharides, the aldehyde (or ketone) group has
reacted with an alcohol group on the same sugar, making the
carbonyl carbon (carbon 1 for an aldose or carbon 2 for a
ketose) asymmetric.
The formation of these ring structures is the result of:
A general reaction b/n alcohols & aldehydes or ketones to
form derivatives called, hemiacetals or hemiketals.
Because of their similarity to the ring compound called pyran
six-membered ring structures are called pyranoses whereas
five-membered ring is known as furanose because of their
similarity to the ring compound called furan. 19
Cyclization of monosaccharides…..
During cyclization of glucose (an aldose), a new asymmetric
center is formed, at C-1(carbonyl carbon)
Thus two isomers of D-glucose exist as α-D-glucose (in which
the OH group at C-1 lies below the plane of the ring) and β-D-
glucose (in which the OH group at C-1 lies above the plane of
the ring).
The carbonyl carbon (C-1 in this case) is called the anomeric
carbon atom and so the α and β forms are called anomers.
In aqueous solution, the α- and β-forms rapidly interconvert via
the open-chain structure, to give an equilibrium mixture. This
process is called mutarotation. It is the spontaneous change in
the specific degree of optical rotation of a freshly prepared
sugar solution - particularly in dilute alkaline solutions.
Eg.
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Reducing property (chemical property)
Sugars that contain a free aldehyde or ketone group can
reduce can reduce the cupric salts, bismuth, silver and picric
acid. Eg. cupric ions (Cu2+) to cuprous ions (Cu+) and hence
are called reducing sugars.
Such sugars can react with chromogenic agents (eg.
Benedict's reagent or Fehling's solution) causing the reagent to
be reduced and colored, with the anomeric carbon of the sugar
becoming oxidized. For eg., addition of alkaline CuSO4 (called
Fehling’s solution) to an aldose sugar produces a red cuprous
oxide (Cu2O) precipitate and converts the aldose to an aldonic
acid, such as gluconic acid.
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2. Oligosaccharides-
Are carbohydrate Conjugates made of 2-10 monosaccharides.
2.1. Disaccharides- the most common oligosaccahrides made up of
two monosaccharide units joined covalently by an O-glycosidic
linkage via a condensation reaction (removal of water).
The glycosidic bond is created between the C-1 of one sugar and
the -OH of another carbon
General formula C12H22O11
reducing or non-reducing depending upon whether the C1-aldehyde
or C2-keto groups were consumed in the linkage or not.
Reducing disaccharides: contain a free anomeric carbon.
A. Maltose: Malt sugar
formed between C-1 and C-4 positions of two glucose units.
The configuration of the anomeric carbon atom involved is the α
form and hence the bond is called an α (1→4) bond or abbreviated
as α-1–4. 23
Maltose is present in germinating cereals and in barley.
Commercial malt sugar contains maltose. It may be formed
during the hydrolysis of starch.
It is hydrolyzed into two glucose molecules by HCl or by the
intestine maltase enzyme.
Isomaltose: it is similar to maltose except that it has an α-1→6-
glucoside linkage
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B. Lactose: Milk sugar
is a disaccharide formed between the anomeric carbon (C-1)
of D-galactose and C-4 of D-glucose.
Since the anomeric carbon of the galactose involved in the
bond is in the β-configuration, the glycosidic bond formed is
called β- (1→4) bond which can be abbreviated as β -1–4.
It is hydrolyzed by HCl or by intestine enzyme, lactase, into
galactose and glucose.
CH2OH CH2OH
O O
OH H H
H
4 1 O 4 H 1
OH H OH H
H H OH
H OH H OH
-D-Galactose -D-Glucose 25
Lactose is digestible by most humans by lactase enzyme present
in small intestine to galactose and glucose.
5% of people from Scandinavia and 90% of Asian adults suffer
from lactose intolerance – deficiency in enzyme lactase.
For those with the deficiency:
Lactose accumulates in small intestine, degraded by intestinal
bacteria producing CO2, hydrogen gas, and organic acids
Symptoms
• Bloating, Nausea, Cramping, Diarrhea
For lactose and maltose, one of the anomeric carbons has been
used to form the bond, leaving the second anomeric carbon free.
Thus both lactose and maltose are reducing sugars.
In contrast, sucrose lacks free reducing end and non-reducing.
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Sucrose is dextrorotatory, but when hydrolyzed by the intestinal
sucrase enzyme or by HCl, the produced fructose and glucose
mixture is levorotatory because of the strong levorotation of
fructose. This is why the levorotatory mixture produced from
sucrose hydrolysis is called invert sugar while sucrose was
dextrorotatory. For the same reason, sucrase is called invertase.
B. Trehalose: is a major constituent of the circulating fluid
(hemolymph) of insects, serves as an energy storage compound.
It is also found in yeasts and other fungi. Here, the two anomeric
carbon atoms of the two α-D-glucose moieties connect each
other by -1,1-glucosidic linkage. The sugar is known as a
stabilizer of proteins and a protector of the plant and animal
tissues from damage by desiccation and freezing. As a result,
trehalose is used in processed foods and medicinal and cosmetic
preparations though it has small supply, depending on extraction
from yeast cells. It is hydrolyzed by the intestinal trehalase
enzyme into two -glucose molecules.
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2.2. Trisaccharides: Raffinose is containing D-galactose, D-
glucose, D-fructose and present in molasses.
2.3. Tetrasaccharides: Stacchyose is composed of two galactose
units and one unit each of glucose and fructose. It is found in
onions.
3. Polysaccharides/ glycans
Are long chains of monosaccharides( >10 monosaccharides /
molecule) joined together by glycosidic bonds
Divided in to two classes based on composition:
1.Homoglycans or homopolysaccharides
are composed of only one type of monosaccharide
Starch
Mixture of 2 types of glucose polymers (amylose and
amylopectin)
a. Amylose
The core part representing 20% of the granule
Is linear, unbranched chain of α(1,4) D-glucose molecules
Each amylose has 2 ends: Non-reducing End (Glucose
molecule with free –OH on C4) & Reducing End (Glucose
molecule with free –OH on C1 – anomeric carbon).
Water-soluble and gives blue color with iodine solution.
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(14)
b. Amylopectin
The outer shell representing 80% of the granule
Main backbone is amylose (linear) with D-glucose molecules in
α(1, 4) linkage
Also has branches: Connect to backbone and to each other by
α(1, 6) linkages
Branch points every 25-30 glucoses
Insoluble in water and gives red color with iodine solution.
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Degradation of starch/amylopectin
Amylose [α(1, 4) linked glucose] is degraded by enzymes called
Amylases in the mouth and intestine to yield maltose and
glucose
Maltose is further degraded to 2 glucoses by maltase in intestine
All glucose is then absorbed by the body and used to make
cellular energy
Additional enzymes are needed to hydrolyze the α(1,6) linkages
between glucoses at the branches – called a “debranching”
enzyme
Dextran: is a highly branched bacterial and yeast polysaccharide
made up of - 1,6 linked poly-D-glucose with -1,3; -1,4; and
-1,2 branches. Dental caries/tooth decay, caused by
Streptococcus bacterium growing on the surface of teeth
synthesizes and secretes dextran by dextran-sucrose.
Dextran is used for the treatment of hypovolumic shock as 32 in
cases of hemorrhagic shock by restoring blood pressure .
Glycogen
Branched glucose polysaccharide
Similar in structure to amylopectin (-1,4 and -1,6-glucosidic
linkages)
But have α-1,6 branches every 8-10 residues (like amylopectin
with more branches)
Stored in liver and muscle as granules or particles (up to 10% of
liver mass and 1-2% muscle mass)
Glycogen gives deep-red color with iodine solution.
Significance of branching
allows several sites for simultaneous synthesis and degradation
Branching makes glycogen compact and coiled = efficient way
to store glucose
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B. Structural homopolysaccharides: cellulose and chitin
Cellulose
make the structure of plant cell wall
water-insoluble straight chain polymer of glucose with β-(1- 4)
linkages with alternating glucose molecules
Although it is indigestible in human, it gives very important benefits
as dietary fibers (prevent constipation by increasing peristalsis;
adsorbs endogenous and exogenous toxins, bile acids and cholesterol
and prevents their absorption into the body=lowering blood
cholesterol).
Its fermentation by large intestinal bacteria gives some vitamins and
volatile fatty acids (particularly butyric acid) that are strong
anticancer agents against colorectal cancer.
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Inulin- is a fructose polymer present in onions.
It is not metabolizable in human body but has a small
molecular weight and is water soluble.
Therefore, its intravenous injection is used to determine the
glomerular filtration rate of the kidney by the test known as
’Inulin clearance test’.
Chitin - is a linear polymer of -N-acetyl-glucosamine units
joined by -1,4-glucosidic linkage.
Make the structure of fungal cell wall and insects exoskeleton
only difference from cellulose is the replacement of the OH at
C-2 with an acetylated amino group. Similar to cellulose,
chitin cannot be digested by vertebrates and is probably the
second most abundant polysaccharide, next to cellulose, in
CH OH CH OH
nature. H
O
2
H
O
2
H H
O 4 1 O 4 1 O
OH H OH H
2 2
H HN C CH3 H HN C 35
CH3
O O n
-D-2-N-Acetyl-glucosamine -D-2-N-Acetyl-glucosamine
Heteropolysaccharides
They provide protection, shape, extracellular support, or site of
recognition for the cells.
They are of two types:
A. Non-nitrogenous heteropolysaccharides: They do not
contain sugar-amines.
Plant gums, mucilages, and Pectins
•Composed of pentoses, hexoses and uronic acids
•Used as emulsifying agents and for the treatment of diarrhea.
Agar
• Composed of the unbranched polymer agarose and the
branched agaropectin.
• Used for supporting material in gel electrophoresis, bacterial
growing culture, for vitamins and drugs packaging capsules.
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B. Nitrogenous heteropolysaccharides: contain sugar amines.
Three types: Proteoglycans, glycoproteins, and glycolipids
1. Proteoglycans
Complexes of polysaccharides called glycosaminoglycans and
core proteins(membrane protein or a secreted protein).
The glycosaminoglycan chain can bind to extracellular
proteins through electrostatic interactions between the protein
and the negatively charged sugar moieties on the proteoglycan.
Proteoglycans are major components of all extracellular
matrices(ECM).
Major components of connective tissue, providing strength and
resilience. e.g. hyaluronic acid Found in cartilage and synovial
fluid.
FIG. Proteoglycan structure,
showing the tetrasaccharide
bridge.
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Glycosaminoglycans are the structural and functional units of
proteoglycans.
The extracellular matrix in the tissues of multicellular animals is
composed of an interlocking meshwork of heteropolysaccharides
and fibrous proteins such as collagen, elastin, fibronectin, and
laminin.
The heteropolysaccharides, called glycosaminoglycans (GAGs;
also named, mucopolysaccharides), are a family of linear
unbranched polymers composed of repeating disaccharide units.
The two repeating units are amino sugar (mainly, N-
Acetylglucosamine or N-acetylgalactosamine) and Uronic acid
(mainly, D-glucuronic acid or L-iduronic acid).
Due to their ionizable -OH and sulfate groups, GAGs have more
negative charges causing to retain much water and making them
highely an incompressible substance
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The major GAGs are: Hyaluronic acid, Chondroitin sulphate,
Dermatan sulphate, Keratan sulphate, Heparin and Heparan
sulphate. glucosaminoglycans
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Peptidoglycans
Found in cell wall of bacteria.
Composed of alternating residues of N-acetylglucosamine
and N-acetylmuramic acid joined by β- (1-4) linkages.
Within the bacterial cell wall, they are cross-linked by short
peptides (containing D-amino acids).
However, the mammalian lysosomal enzyme lysozyme kills
bacteria by hydrolyzing the β1-4 glycosidic bond.
Penicillin and related antibiotics kill bacteria by preventing
synthesis of the cross-links, leaving the cell wall too weak to
resist osmotic lysis.
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2. Glycoproteins
Glycoproteins contain covalently linked oligosaccharides that
are smaller but more structurally complex, and therefore more
information-rich, than GAGs.
Oligosaccharides covalently linked to Asp or Ser/Thr residues
They are found in eukaryotic cells(Golgi, secretory granules,
and lysosomes).
They are found on the outer face of the plasma membrane, in
the extracellular matrix, and in the blood.
Carbohydrate forms a glycosidic linkage with the – OH of Ser
or Thr through its anomeric end (O-linked), or an N-glycosyl
link through the amide of Asn (N-linked).
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Examples: antibodies, the intrinsic factor important for absorption
of vitamin B12, plasma transport proteins, enzymes (e.g., the blood
clotting cascade), and as structural components of the extracellular
matrix, e.g, collagen.
Functions
Serve as markers to
identify a cell type (Cell
surface markers)
Can serve as antigenic
determinants (how
antibody recognizes the
protein) on proteins
The difference between
blood types is due to
glycosylation of red
blood cell proteins
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3. Glycolipids/ Lipopolysaccharides
Are carbohydrate-lipid conjugates in which the hydrophilic head
groups are oligosaccharides, which, as in glycoproteins, act as
specific sites for recognition by carbohydrate-binding proteins.
Bacterial cell wall lipopolysaccharides and the human ABO blood
group cell membrane antigens are important examples.
Glycolipids and glycosphingolipids in plants and animals and
lipopolysaccharides in bacteria are components of the cell envelope,
with covalently attached oligosaccharide chains exposed on the
cell’s outer surface.
Carbohydrates as Informational Molecules
Carbohydrates serve as information-rich molecules that guide
many biological processes. Cells use specific oligosaccharides to
encode important information about intracellular targeting of
proteins, cell-cell interactions, cell differentiation and tissue
development, and extracellular signals. 43
Examples include:
1. Create entry mechanisms for microbial pathogens
Some microbial pathogens have proteins called lectins that help
their adhesion to host cells or toxin entry into cells(eg. Influenza
virus, Helicobacter pylori , Cholera toxin)
2. Asialoglycoprotein -receptor interactions
asialoglycoprotein- lectin interaction triggers endocytosis and
destruction of the particular glycoprotein by liver cells (removing
old RBCs, unwanted hormones, antibodies & the like from the
blood).
3. Movement of immune cells (T lymphocytes) through the
capillary wall, from blood to tissues, at sites of infection or
inflammation is enhanced though P-selectin (a type of lectin).
4. Interaction of sperm with ovulated eggs- is through
hyaluronidase, which allowing sperm entry.
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