Download Carbohydrates: Structure and Biological Function:

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Carbohydrates: Structure and Biological Function:
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Glucose, fructose, sucrose, starch and cellulose- these chemical names are
common words in everyday use
They are most abundant members of the large and important class of
biomolecules called carbohydrates
Biologist believe that the carbohydrates make up a higher percentage of
biomass than any other biomolecule class
The carbohydrates are defined as compounds having polyhydroxy
aldehyde or ketone since they have reactive aldehyde and ketone
functional groups and multiple hydroxyl groups
The hydroxyl groups provide the possibility of strong intra or inter chain
interactions via hydrogen bonds
In addition to predominant elements carbon, hydrogen and oxygen, some
carbohydrates also contain sulfur, nitrogen or phosphorus
Like the other major classes of biomolecules (proteins, nucleic acids,
lipids), the carbohydrates are found in all forms of life and serve many
different functions:
•
The carbohydrates are probably best known for their role in energy
metabolism. Some compounds in this class (for example, glucose and
fructose) serve as fuel molecules for immediate use by organisms,
where other compounds (starch and glycogen) are chemicals stores for
future energy needs in plants and animals
•
Like proteins, some carbohydrates perform structural functions,
providing scaffolding for bacterial and plant cell walls, connective
tissue such as cartilage in animals and exoskeleton shell in
arthropods
•
The monosaccharides ribose and deoxyribose, as components of
the nucleic acids, serve a chemical structural role (RNA and DNA)
and as polar sites for catalytic processes (RNA, ribozymes)
•
Carbohydrates are covalently combined with proteins and complex
lipids on cell surfaces to act as informational markers for
molecular roles in cell-cell recognition processes and in signal
transduction
 Here we first introduce the unique structures and reaction of biologically
important carbohydrates and then turn to their presence in proteins and
involvement in biological processes
 Diseases associated with carbohydrates include:
• Diabetes mellitus
• Galactosemia - inability to metabolize galactose inherited defects in enzyme
• Glycogen storage diseases - a group of inherited diseases characterized by
deficient mobilization of glycogen or deposition of abnormal forms of
glycogen leading to muscle weakness or even death
• Lactose intolerance lactase deficiency leading to diarrhea and intestinal
discomfort
 Classification:
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Monosaccharides and Related Compounds:
• The simplest carbohydrates, sometimes referred to as monosaccharides or
sugars, are either polyhydroxy aldehydes (aldoses) or polyhydroxy
ketones (Ketoses)
• They can be derived from poly alcohols (polyols) by oxidation of one
carbinol group to a carbonyl group
• For example, the simple three-carbon triol, glycerol, can be converted
either to the aldotriose i.e. glyceraldehyde or to the ketotriose dihydroxyacetone, by loss of two hydrogens
Fig 12.1, Zubay
• Since the middle carbon of glyceraldehyde is connected to four different
substituents, it is a chiral center leading to two possible forms of
glyceraldehyde i.e. stereoisomers (enantiomer; D and L forms)
• We may visualize the four, five and six carbon sugars (tetroses, pentoses
ad hexoses) as arising from the triose through the stepwise condensation
of formaldehyde to either glyceraldehyde or dihydroxyacetone
• Indeed this may be the way in which sugars arose in prebiotic times but
biosynthesis of sugars occurs by other means
Fig 12.2, Zubay
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Fig 12.3, Zubay
Monosaccharides cyclize to form Hemiacetals;
• Aldehyde can add hydroxyl compounds to the carbonyl group
• If molecule of water is added, the product is an aldehyde hydrate
and if a molecule of alcohol is added, the product is a hemiacetal.
Further the addition of a second alcohol results in an acetal
Fig 12.4, Zubay
• The carbonyl group of a ketone reacts with an –OH group in a
similar fashion to form a hemiketal
P 202, Boyer 3rd Ed
• Sugars readily form intramolecular hemiacetals in cases in which
the resulting compound has a five or six member rings
• Hemiacetal formation was first observed in optical studies on Dglucose
• The optical rotation ([α]D) of a freshly dissolve sample of Dglucose changes with time because it possesses two stereoisomeric hemiacetal (anomers) that are interconvertible in solution
Fig 12.5, Zubay
• The optical rotation of a freshly prepared solution of either of these
compounds eventually approaches an intermediate value that
depends on the equilibrium between the two anomers
P 202
1
-The α designation for the D
series indicates that the
aldehyde of the C-1 hydroxyl
group is on the same side of the
structure as the ring oxygen in
Fisher projection while in β
configuration the aldehyde is
on the opposite side
- When sugar is dissolved in
water, the two hemiacetals are
in equilibrium with the straight
chain hydrated form
- Conversion of one hemiacetal
form into the other is called
mutarotation
- Equilibrium is reached
without an added catalyst in a
few hours at room temperature
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•
Hemiacetals with five member rings are called furanose and
hemiacetal with six member rings are called pyranose
• There are various way to represent glucose
Fig 12.6, Zubay
 Many Monosaccharides are Physiologically Important;
Table 14.2, Murray 27th Ed
Table 14.3, Murray 27th Ed
 Reaction of Monosaccharides;
• With several possible kinds of functional groups present in an
aqueous carbohydrate solution (hydroxyl groups, hemiacetal or
hemiketal and aldehyde or ketone groups), diverse chemical
reactions and unique products can be expected
• Here we will discuss those reactions that are either of biological
significance or used for identification and analysis of
carbohydrates
• Oxidation-Reduction;
o
The complete metabolic breakdown of glucose to CO2
and H2O is a process involving several oxidation steps,
the details of which will be discussed later on
o
The functional group most susceptible to oxidation is the
aldehyde group, which produces a carboxylic acid group
Many oxidizing agent including Tollens’ reagent [silver
ammonia complex, Ag(NH3)+2 ] and cupric ion (Cu 2+),
are used to identify the presence of reducing sugars
o
Reducing sugars are those that contain a free aldehyde
group and are capable of reducing metal ions in solution
Fig 7.11, Boyer 3rd Ed
o
Reduction of the aldehyde or ketone group of a
carbohydrate is also of biological importance
o
The reduction of aldehyde group in glucose yields sorbitol,
a sweetening agent
o
Another form of reduced carbohydrates are deoxysugars
Fig 7.12, Boyer 3rd Ed
• Esterification;
o
Esters are formed by reaction of hydroxyl groups with
acids
o
dehydrogenase
o
The most important biological esters of carbohydrates
are the phosphate esters made in the laboratory with
phosphoric acid
o
In the cell, phosphate esters are produces not by using
the very acidic phosphoric acid, but most often by
transfer of phosphate group from ATP to carbohydrate
hydroxyl group, a reaction catalyzed by enzymes called
kinases
Fig 7.13, Boyer, 3rd Ed
• Amino Derivatives;
o
The replacement of a hydroxyl group on a carbohydrate
by an amino group results in an unusual class of
compounds, the amino sugars
o
Two amino sugars that occur within nature are D-2aminoglucose (glucosamine) and D-2-aminogalactose
(galactosamine)
Glucosamine and its acetylated derivatives, Nacetlyglucosamine and N-acetylmuramic acid are found
as structural components of bacterial cell walls
o
Similarly, N-acetylglucosamine is a component of chitin,
a polymer found in the exoskeleton of insects and
crustaceans and
o
It is also a major structural unit of chondroitin sulfate, a
polymeric component of cartilage
o
The acidic amino sugar N-acetylneuraminic acid (sialic
acid), derived from the carbohydrate rhamnose, is a
component of glycoproteins and glycolipids
Fig 7.14, Boyer 3rd Ed
Window of Biochemistry 7.1
Glycoside Formation;
i. O-Glycosides
o
When carbohydrates are reacted with hydroxyl groups
under anhydrous mildly acidic conditions, a new linkage,
an O-glycosidic bond, is formed
Fig 7.15, Glick 3rd Ed
o
The hydroxyl group of another carbohydrate molecule
can substitute for the alcohol in the reaction, linking two
monosaccharides to make disaccharides and
polysaccharides
o
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Fig 7.16, Boyer 3rd Ed
Fig 7.17, Boyer 3rd Ed
N-Glycosides
o
The N-H group of amines can substitute for hydroxyl
groups and react at the anomeric carbon center of
carbohydrates
o
This linkage is called an N-glycosidic bond
o
This type of bond is of paramount importance in the
construction of nucleotides such as ATP and in the
nucleic acids RNA and DNA
Fig 7.18, Boyer 3rd Ed
Glycosides are widely distribute in nature; the aglycone may be
methanol, glycerol, a sterol, a phenol or a base such as adenine
The glycosides that are important in medicine because of their
action on the heart (cardiac glycosides) all contain steroids as the
aglycone
These include derivatives of digitalis and strophanthus such as
ouabian, an inhibitor of the Na+-K+ ATPase of cell membrane
P 259, Boyer 3rd Ed
Other glycosides include antibiotics such as streptomycin
Degradation product
of cellulose
Exclusively present in milk
of mammals
Abundant in sugar
cane and sugar beat
Degradation product of
starch
 Polysaccharides;
• Serving as monomeric units, the monosaccharides and their
derivatives are linked together to form a wide variety of
polysaccharides that play diverse biological role
• The stability of the variety of O-glycosidic bond makes it possible
for monosaccharides to combine into structurally distinct and
biologically useful polymers
• To define the structure of a polysaccharide, several structural
features must be recognized:
i. The identity of monomeric units
ii. The sequence of monosaccharide residues (if more than one
kind is present)
iii. The type of glycosidic bonds linking the units
iv. The approximate length of the chain (the approximate number
of monosaccharide units)
v. The degree of branching
• Homopolysaccharides are composed of a single type of
monosaccharide unit whereas
• Heterosaccharides contain two or more types of monosaccharides
•
The term oligonucleotide is used to denote polysaccharides with
small number of monosaccharides (usually fewer than 10)
• Glucose and its derivative are most common monomeric units.
However, other monosaccharides, including fructose, galactose
and derivatives are found in a natural polysaccharides
• In some polysaccharides, the individual strands are cross-linked by
short peptides. These compounds are component of bacterial cell
walls and called peptidoglycans
• Storage Polysaccharides;
o
Plants and animals store the energy molecule glucose in
starch and glycogen, respectively
o
These polysaccharides are stored in the cell in
cytoplasmic packages called granules
Fig 7.19, Boyer 3rd Ed
o
Starch is present in the chloroplasts of plants, where it is
produced by photosynthetic energy and especially
abundant in potatoes, corn and wheat
o
Glycogen granules are present primarily in liver and
muscle cells of animals
o
Because of numerous hydroxyl groups on the two
polysaccharides, much water is associated by hydrogen
bonding
In fact, each gram of glycogen stored in liver or
muscle tissue is hydrated with 2 gram of water
i. Starch
A mixture of two types of polymeric glucose, amylose
and amylopectin
When starch is ingested in the human diet, its degradation
begins in the mouth
The salivary enzyme α-amylase catalyzes the hydrolysis
of O-glycosidic bonds, yielding the disaccharides maltose
and oligosaccharide products
Fig 7.20, Boyer 3rd Ed
ii. Glycogen
Animals store glucose for energy metabolism in the
highly branched polymer, Glycogen
Fig 7.20, Boyer 3rd Ed
This polymer is identical to amylopectin except that it has
more numerous (1
6) branches i.e. about one every
tenth glucose residue in the main chain and a much
higher average molecular weight (several million)
Fig 7.21, Boyer 3rd Ed
o
- Molecular weight of amylose may range from few
thousand to 500,000
- The branch point occur on the average of
every twenty fifth glucose residue
- The average molecular weight of
amylopectin is about 1 million
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Like amylopectin, glycogen consists of a single reducing
end and many non reducing ends
This is of significance in the mobilization (release) of
glucose units for energy metabolism
The enzyme glycogen phosphorylase catalyzes the
removal of glucose residues from the numerous non
reducing ends, providing abundant supplies of glucose
when necessary
Although glycogen is present both in liver and muscle
cells, it is much more abundant in hepatic cells, where it
may account for as much as 10% of the wet weight and
only about 1% of the weight of muscle cells is glycogen
The extended chains and the angle of the α(1
4)
glycosidic bond of amylose, amylopectin and glycogen
make it possible for then to fold into tightly coiled helical
structures
Fig 7.22, Boyer 3rd Ed
Approximately six glucose residues make up one turn of
the helix
Other minor form of storage polysaccharides are present
in nature
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Dextran, found in yeast and bacteria consists of
glucose residues connected in to a main chain via α
(1
6) glycosidic bonds with occasional branches
formed by α (1
2), α (1
3) and α (1
4)
glycosidic bonds
Bacteria growing on teeth produce extra cellular daextran
that accumulates and becomes an important component of
dental plaque
Inulin, a homo polymer of D-fructose connected by β
(1 2) glycosidic linkages, is found in artichokes and
other vegetables
• Structural Polysaccharides
o
Some polysaccharides such as cellulose, chitin and
mucopolysaccharide are synthesized inside cells but
extruded to the outside to provide a protective wall or
lubricative coating to cells
o
Cellulose is the major structural component of wood and
plant fibers
o
This glucose polymer is extremely abundant in nature,
making up over 50% of the organic matter in biosphere
o
It is unbranched polymer connecting D-glucose units
together by β(1
4) glycosidic linkages
o
o
o
o
o
o
o
Fig 7.23, Boyer 3rd Ed
Fig 12.11, Zubay
The average molecule of cellulose contains between
10,000 and 15,000 glucose residues
The β configuration of the glycosidic bonds allows
cellulose to form very long and straight chains that differ
from the helical coils of starch and glycogen
The extended chains of cellulose can associate into
bundles of parallel chains fibrils
Fig 12.10 Zubay
This strong and rigid networks, which provide the
scaffolding for plant cell walls, are held together by intra
and intermolecular hydrogen boning
This strong, stabilized, sheet like arrangement of atoms
make cellulose a useful product for clothing, paper,
cardboard and building materials
Although a portion of our diet consists of vegetables and
fruits containing cellulose, we are unable to extract
cellular energy from this glucose polymer
Animal do not produce enzymes that can catalyze the
hydrolysis of β(1
4) glycosidic bonds between the
glucose residues in cellulose
o
o
o
o
o
o
o
Wood-rot fungi and some bacteria obtain nutrient glucose
by synthesizing and secreting enzymes (cellulase) that
catalyze the hydrolysis of the β(1
4)
These organisms are largely responsible for the decaying
of dead wood in forest
Ruminant animals (cattle, sheep, goat, camels, giraffes)
are able to use cellulose as a nutrient source because their
second stomachs contain bacteria that secrete cellulases
In a similar fashion, termites can digest wood cellulose
because their intestinal tracts contain Trichomypha, a
symbiotic microorganism that produces cellulase
Cellulose and its derivatives do, however, perform an
essential role in the diets of animals as bulk fiber or
“roughage” to assist the digestion and absorption of
nutrients
Another important polysaccharide component of plant
cell walls is pectin, a polyuronic acid, a C4 epimer of the
glucose derivative, D-glucuronic acid
Fig 7.24, Boyer 3rd Ed
Pectin extracted from plans is used as a gelling agent in
the preparation of jams and jellies
o
o
o
o
o
o
o
The protective exoskeleton of arthropods (insects, crabs,
lobsters) are composed primarily of the un-branched
homopolysaccharides chitin
P 218, Boyer 3rd Ed
This polymer is also found in smaller amounts in the cell
walls of yeast, fungi and algae
The monomeric building block of chitin is the glucose
derivative N-acetylglucosamine, linked in β (1 4)
glycosidic bonds
Fig 7.25, Boyer 3rd Ed
P 218, Boyer 3rd Ed
Like cellulose, chitin exits in extended chains that are
associated into fibers by intra and intermolecular
hydrogen bonding
Because human has no enzymes that can catalyze the
hydrolysis of β (1
4) linkages in chitin, it is
indigestible
Some structural polysaccharides are found in
connective tissue (cartilages and tendons) or extra cellular
matrix (ground substance) of higher animals
The extra cellular matrix is gel like martial that acts as
glue to hold cells together
A group of polymers, called mucopolysaccharides,
provide a thin, viscous, jellylike coating to cells
o
The most abundant in this class of polysaccharides is
hyaluronic acid which has alternating monomeric units of
N-acetlyglucosamine and D- glucuronic acid
Fig 7.26, Boyer 3rd Ed
o
Hyaluronic acid serves as a lubricant in the synovial fluid
of joints and is found in the extra cellular matrix of
connective tissues
o
Another component of the extra cellular matrix is
chondroitin sulfate, a hetero-polymer
mucopolysaccharides
o
Like hyaluronic acid, it is composed of two alternating
monomer units, N-acetylgalactosamine sulfate and Dglucuronic acid
Fig 7.27, Boyer 3rd Ed
• Structural Peptidoglycans
o
The rigid cell walls of bacteria, which provide physical
protection, are composed primarily of an un-branched
heteropolymer of alternating N-acetylglucosamine and Nacetylmuramic acid
o
The monomer units are linked into an extended backbone
by β(1
4) glycosidic bonds
o
The rigidity and strength of bacterial cell walls are
consequences of a network of peptide cross-links between
strands of the linear polysaccharides
o
The amino acid composition and sequence of the peptide
links vary from bacterium to bacterium
o
In Gram-positive bacterium Staphylococcus aureus, two
sets of peptides, a tetra-peptide and a penta-peptide of
five glycine residues, form the cross-links
Fig 7.28, Boyer 3rd Ed
o
Summary of the composition and biological roles of the
polysaccharides is given in this table
Table 7.3, Boyer 3rd Ed
• Glycoproteins - Structure
o
Proteins that have covalently bonded carbohydrate units
attached to them are called glycoproteins
o
These proteins are involved in many biological functions
including immunological protection, cell-cell recognition
events, blood clotting, signal transduction processes and
host-pathogen interactions
o
o
o
Carbohydrate portion of a glycoprotein usually
constitutes 1% to 30% of the total weight, although
some glycoproteins contain as much as 50% to 60%
carbohydrate
The most common monosaccharides found in
glycoproteins are glucose, mannose, galactose, fucose, Nacetylgalactosamine, N-acetylglucosamine and Nacetylneuraminic acid (sialic acid)
Fig 7.29, Boyer 3rd Ed
o
o
Sugars are attached to proteins as branched
oligosaccharide units, usually containing fewer than 15
carbohydrates residues
Two important types of covalent linkages involved in the
attachment of sugars to protein
Fig 7.30, Boyer 3rd Ed
o
Additional carbohydrates are usually linked to the first
monosaccharide on the glycoprotein
Fig 7.31, Boyer 3rd Ed
o
Glycoproteins with unique oligosaccharide compositions
and sequences are said to be “information rich”
They are frequently found on cell surfaces where they
serve as markers to identify the type of cell
o
Recognition of surface oligosaccharides is involved in
diverse processes blood type determination, antibody
action, cancer initiation, turnover of aged proteins and
viral growth
o
It has also been discovered that attaching sugar tails to
medicinal proteins enhances the therapeutic potency of
proteins
o
Many new discoveries about the structure and action of
glycoproteins are coming from the study of proteins that
act as “antifreeze agents” in the blood of arctic fish living
in subzero waters
o Glycoprotein – Function
i. Glycoproteins and Cancer
When cells transformed from a normal state to a
malignant state, changes take place in the
glycoproteins on the cell surface
These changes usually caused in the cancerous
cell by a deficiency of enzymes called
glycosyltransferases that attach carbohydrates to
membrane proteins by forming O- and Nglycosidic bonds
o
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Because of a phenomenon called contact
inhibition, normal cells usually stop growing
when their surface touch
Cancerous cells with altered cell surfaces do not
recognize the message to stop growing so they
pile up on each other
ii. Protein Turnover
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Oligosaccharides are also used to mark proteins
for age
Glycoproteins in the serum are constantly
“turned over” with newly synthesized ones
taking the place of the aged ones
In general, removing of carbohydrate units from
glycoproteins almost always increases their
susceptibility to proteolytic degradation
Fig 7.32, Boyer 3rd Ed
Liver cells have on their surfaces receptor
protein sites that recognize aged glycoproteins
lacking sialic acid
Such glycoproteins are taken up by liver cells
and degraded by proteolytic enzymes to free
amino acids
iii. Viral Growth
Many viruses including herpes simplex, hepatitis
B, influenza and HIV contain protein on their
surfaces that have potential sites for linkages of
oligosaccharides
Carbohydrates may be linked to these proteins
using host cell enzymes to produce
glycoproteins that are indistinguishable from
those on host cells
This allows the virus to thrive because it avoids
immune surveillance by the host cell and can
also attach and fuse to host cell receptors
For example HIV envelop protein gp 120 has
20-25 asparagine residues that are potential site
for attachment of oligosaccharide units by Nglycosidic linkage
iv. Antifreeze Glycoproteins
Fish living in the subzero waters of the Antarctic
and Arctic are protected from freezing by the
presence of antifreeze glycoproteins (AFGPs) in
their blood
The glycoproteins act by lowering the freezing
temperature of water
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Each AFGP has large number of repeating
units consisting of tripeptide Ala-Thr-Ala and a
disaccharide usually β-D-galactosyl-(1
3)-α
-N-acetyl-D-galactosamine is covalently linked
to each threonine hydroxyl group by an Oglycosidic bond
Japanese Biochemists have found that the
protein having only a single tripeptide unit with
disaccharide causes a measurable lowing of the
freezing temperature of water, although the
naturally occurring glycoproteins usually have
several tripeptide-disaccharide units
They have shown by NMR spectroscopy that the
glycoproteins fold to expose a polar, hydrophilic
side (with carbohydrates) that interacts strongly
with ice crystals, thus lowering the freezing
temperature
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