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2013-11-26
Carbohydrates of biological
importance
General characteristics
Most carbohydrates are found naturally in bound form rather
than as simple sugars
Polysaccharides (starch, cellulose, inulin, gums)
Glycoproteins and proteoglycans (hormones, blood
group substances, antibodies)
Glycolipids (cerebrosides, gangliosides)
Glycosides
Mucopolysaccharides (hyaluronic acid)
Nucleic acids
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Nature of Carbohydrates
Carbohydrates are carbon compounds that contain
large quantities of hydroxyl groups.
The simplest carbohydrates also contain either
an aldehyde moiety (these are termed
polyhydroxyaldehydes) or a ketone moiety
(polyhydroxyketones).
Carbohydrates classification
The monosaccharides are also called simple sugars
and have the formula (CH2O)n.
Monosaccharides - simple sugars, with multiple
hydroxyl groups.
Based on the number of carbons (e.g., 3, 4, 5, or 6) a
monosaccharide is a triose, tetrose, pentose, or
hexose, etc.
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Monosaccharides, either aldoses or ketoses, are often given
more detailed generic names to describe both the important
functional groups and the total number of carbon atoms.
Thus, one can refer to aldotetroses and ketotetroses,
aldopentoses and ketopentoses, aldohexoses and ketohexoses,
and so on.
Sometimes the ketone-containing monosaccharides are named
simply by inserting the letters-ul-into the simple generic terms,
such as tetruloses, pentuloses, hexuloses, heptuloses, and so
on.
Monosaccharides consist typically of three to seven carbon atoms
and are described either as aldoses or ketoses, depending on
whether the molecule contains an aldehyde or a ketone group
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Aldohexoses
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Sedoheptulose (The Pentose Phosphate Pathway)
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Polyhydroxy aldehydes and ketones often containing
chiral centers
Optical isomers
(enantiomers)
Carbohydrates - Stereochemistry
The configuration around every chiral carbon is different
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Stereoisomers that are mirror images of each other are called
enantiomers, or sometimes enantiomeric pairs.
Pairs of isomers that have opposite configurations at one or more
of the chiral centers but that are not mirror images of each other
are called diastereomers or diastereomeric pairs.
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Sugar molecules that differ in configuration at only
one several chiral centers are called epimers
Mannose and galactose are epimers of D-glucose (at C-2 and C-4, respectively).
Fischer projection of glyceraldehyde
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GLUCOSE
D or L refers to the configuration of the highest numbered asymmetric
carbon (farthest from aldehyde or ketone groups)
Cyclic Structures and Anomeric Forms
Although Fischer projections are useful for presenting
the structures of particular monosaccharides and their
stereoisomers , they ignore one of the most
interesting facts of sugar structure—the ability to
form cyclic structures with formation of an additional
asymmetric center.
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Formation of hemiacetals and hemiketals
Alcohols react readily with aldehydes and ketones to form
hemiacetals and hemiketals.
Pentoses and hexoses can cyclize, as the aldehyde or
keto group reacts with a hydroxyl on one of the distal
carbons.
E.g., glucose forms an intramolecular hemiacetal by
reaction of the aldehyde on C1 with the hydroxyl on
C5, forming a six-member pyranose ring, named
after the compound pyran.
The representations of the cyclic sugars are called
Haworth projections.
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All monosaccharides have the ability to cyclize and form ringed
structure
Aldoses cyclize to produce cyclic hemiacetals (forming a pyranose sugar)
and ketoses cyclize to produce hemiketals (forming a furanose sugar)
Formation of the two cyclic forms of Dglucose:
anomer alpha (α) -OH is down in
Haworth projection
beta (β) -OH is up in Haworth projection
Isomeric forms of monosaccharides that differ
only in the configuration about the hemiacetal
or hemiketal carbon atom are called anomers.
The α and β anomes of D-glucose
interconvert in aqueous solution by
a process called mutarotation.
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Rules for drawing Haworth projections
draw either a six or 5-membered ring including
oxygen as one atom
O
O
most aldohexoses are six-membered
aldotetroses, aldopentoses, ketohexoses are 5membered
Rules for drawing Haworth projections
next number the ring clockwise starting next to the
oxygen
5
O
O
1
4
3
2
1
4
3
2
if the substituent is to the right in the Fischer
projection, it will be drawn down in the Haworth
projection (Down-Right Rule)
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Rules for drawing Haworth projections
for D-sugars the highest numbered carbon (farest
from the carbonyl) is drawn up.
For L-sugars, it is drawn down
for D-sugars, the OH group at the anomeric
position is drawn down for α and up for β.
For L-sugars α is up and β is down
Formation of glucose hemiacetal
In the α-anomer the hemiacetal –OH group is on the same side of the
Fischer projection as the oxygen at the configurational carbon
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Isomeric forms of monosaccharides differ only in their
configuration about the hemiacetal or hemiketal carbon atom
are called anomers
The hemiacetal or carbonyl carbon is called the anomeric
carbon
Formation of fructose hemiketal
The α anomer of fructose has the anomeric -OH group down, trans to
the terminal -CH2OH group. The β anomer has the anomeric -OH
group up, cis to the terminal -CH2OH.
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Mutarotation – the change in the specific rotation that
accompanies the interconversion of the α to β anomers in
aquesous solution
Many derivatives of monosaccharides are found in
nature.
These include
Oxidized forms in which the aldehyde and/or alcohol functional groups are
oxidized to carboxylic acids
Phosporylated forms in which phosphate is added by ATP to form
phosphoester derivatives
Amine derivatives such as glucosamine or galactosamine
Acetylated amine derivatives such as N-Acetyl-GlcNAc (GlcNAc) or
GalNAc
Lactone forms (intramolecular esters) in which an OH group attacks a
carbonyl C that was previously oxidized to a carboxylic acid
Condensation products of sugar derivatives with lactate
(CH3CHOHCOO-) and pyruvate, (CH3COCOO- ), both from the glycolytic
pathway, to form muramic acid and neuraminic acids, (also called sialic
acids), respectively.
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Reduction-oxidation reactions of
carbohydrates
Like all other aldehydes, aldose sugars are easily
oxidized to yield carboxylic acids.
When the aldehyde function of an aldose is oxidized to a
carboxylic acid the product is called an aldonic acid (a mild
oxidizing agent such as bromine water must be used for this
conversion).
When oxidation takes place only on carbon C6 the product is
called an uronic acid
If both ends of an aldose chain are oxidized to carboxylic acids
the product is called an aldaric acid.
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Sugar acids
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Aldonic and aldaric acids form lactones
Reduction
either done catalytically (hydrogen and a catalyst) or
enzymatically
the resultant product is a polyol or sugar alcohol (alditol)
glucose forms sorbitol (glucitol)
mannose forms mannitol
fructose forms a mixture of mannitol and sorbitol
glyceraldehyde gives glycerol
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Sugar alcohols are very useful
intermediates
Mannitol is used as an osmotic diuretic
Glycerol, myoinositol are important in lipid
metabolism
Glycerol is used as a humectant and can be nitrated to
nitroglycerin
Ribitol constituent of riboflavin/flavin coenzymes
Other important ones are xylitol and sorbitol
used in food and pharmaceutical processing
sugarless candies, gums have sorbitol in them
Reduction of Glucose
Sorbitol, also known as glucitol, is a sugar alcohol the body metabolises slowly.
Sorbitol does not diffuse through cell membrane easily and therefore accumulates, causing
osmotic damage.
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SORBITOL
Sorbitol is produced naturally by the body, but
sorbitol is poorly digested by the body.
Both fructose and sorbitol are found in the human
lens, where they increase in concentration in diabetes
and may be involved in the pathogenesis of diabetic
cataracts
Diabetic retinopathy and neurophathy may be related
to excess sorbitol in the cells of the eyes and nerves.
ALDITOLS (ALCOHOLS)
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Deoxy sugars
The deoxy sugars are monosaccharides with one or more
hydroxyl groups replaced by hydrogens.
Deoxy sugars also occur frequently in glycoproteins and
polysaccharides.
L-Fucose and L-rhamnose, both 6-deoxy sugars, are
components of some cell walls, and rhamnose is a component
of ouabain, a highly toxic cardiac glycoside found in the bark
and root of the ouabaio tree (Ouabain is used by the East
African Somalis as an arrow poison).
6-deoxy-L-mannose (L-rhamnose) is used as a fermentative
reagent in bacteriology
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6-deoxy-L-galactose
6-deoxy-L-mannose
Special monosaccharides: amino sugars
Constituents of glycosaminoglycans (GAG)
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SUGAR DERIVAIVES - Amino sugars
β D N-acetylglucosamine
Muramic acid and neuraminic acid, which are
components of the polysaccharides of cell
membranes of higher organisms and also bacterial
cell walls, are glucosamines linked to three-carbon
acids at the C-1 or C-3 positions.
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N-acetylneuraminic acid (NANA)
N-acetylneuraminic acid,
which is derived from
N-acetylmannosamine and
pyruvic acid, is an important
constituent of glycoproteins
Neuraminic acid (an amine
isolated from neural tissue)
forms a C-C bond between the
C-1 of N- acetylmannosamine
and the C-3 of pyruvic acid .
N-acetylneuraminate, (also called sialic acid) is
often found as a terminal residue of oligosaccharide
chains of glycoproteins.
Sialic acid imparts negative charge to glycoproteins,
because its carboxyl group tends to dissociate a
proton at physiological pH.
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In muramic acid (thus named as an amine isolated
from bacterial cell wall polysaccharides; murus is
Latin for “wall”), the hydroxyl group of a lactic acid
moiety makes an ether linkage to the C-3 of
glucosamine .
Phosphate derivatives
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Phosphate derivatives
Carbohydrates - Glycosides
Glycosides (replace suffix –ose with –oside) → Reaction at C1
Hemiacetal/Hemiketal + Alcohol -> O- Glycoside → Polysaccharides
Hemiketal/Hemiketal + Amine -> N-Glycoside
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Condensation reactions: acetal and ketal formation
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Glycosides can be with many types of molecules including another
sugar (oligosaccharides) . Disaccharides contain a glycosidic bond
anomeric carbon
Formation
of
maltose
The glycosidic bond protects the
anomeric carbon from oxidation.
Glu(α1→4)Glu
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A common disaccharide is lactose, which is
found only in milk.
β form
The anomeric carbon of the βD-galactose molecule reacts
with the C-4 hydroxyl group of
the β-D-glucose molecule to
form the glycosidic bond .
The bond is designated a
β(1→4) bond, indicating the
configuration of the anomeric
carbon (β), the number of the
anomeric carbon (1), and the
number of the carbon (of the
second sugar) to which it is
linked (4).
Sucrose
Sucrose is widely distributed in nature and occurs in
most plants; rich sources of sucrose include sugar
cane (20% sucrose), sugar beet (15–20%), mangolds
and carrots.
Sucrose is the sugar of familiar use in the domestic
household.
When sucrose is heated to a temperature of 160°C it
forms barley sugar, and at 200°C forms caramel.
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Important to remember:
The α in α-1→4- refers only to the fact that the
first glucopyranose is the α anomer.
Only anomeric carbons are designated α or β ,
not the other carbons in the carbohydrate.
For sucrose, the α in α-1 indicates that the
glucopyranose is the α anomer and β- 2 indicates
that the fructofuranose is the β anomer.
The correct specification of the configuration of the
anomeric carbon is critical: an α(1→4) linkage is
not the same thing as a β(1→4) linkage
Reducing sugars
Sugars with a free anomeric carbon (straight chain
exposing the aldehyde) can reduce certain
oxidizing agents.
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Maltose is reducing sugar
Reducing sugars
Lactose: Gal(β 1->4)Glc
Since Glc is attached to Gal
through the OH on C4, its
anomeric carbon, C1, could
revert to the noncyclic
aldehyde form.
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Sucrose: Glc(α 1→2)Fru
Sucrose: is composed of one
molecule of glucose and
fructose joined together
through a α-1, β-2-glycoside
linkage.
Since both functional reducing
groups are involved in the
glycoside linkage, sucrose
does not possess reducing
properties.
Sucrose: Glc(α 1→2)Fru.
Some common disaccharides
reducing sugar
non reducing sugar
non reducing sugar
Non reducing sugars are
named as glycosides.
Glc(α1→2β)Fru
configuration of
the anomeric
Carbon
carbons joined by
The glycosidic bond
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Digestion of Carbohydrates
Monosaccharides
Do not need hydrolysis before absorption
Very little (if any) in most feeds
Di- and polysaccharides
Relatively large molecules
Must be hydrolyzed prior to absorption
Hydrolyzed to monosaccharides
Only monosaccharides can be absorbed
Carbohydrate Digestion
Mouth
Salivary amylase
Breaks starches down to maltose
Plays only a small role in breakdown because
of the short time food is in the mouth
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Carbohydrate Digestion
Pancreas
Pancreatic amylase
Hydrolyzes alpha 1-4 linkages
Produces monosaccharides, disaccharides,
and polysaccharides
Major importance in hydrolyzing starch and
glycogen to maltose
Polysaccharides
Amylase
Disaccharides
Digestion in Small Intestine
Digestion mediated by enzymes synthesized
by cells lining the small intestine (brush
border)
Disaccharides
Brush Border Enzymes
Monosaccharides
* Exception is β-1,4 bonds in cellulose
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Digestion in Small Intestine
Sucrose
Sucrase
Glucose + Fructose
* Ruminants do not have sucrase
Maltose
Lactose
Maltase
Lactase
Glucose + Glucose
Galactose + Glucose
Structures of the following compounds are
obligatory for the control test of carbohydrates
General scheme of hemiacetal and hemiketal formation.
Structures of D-glucose and D-fructose presented in open chain, Fischer projection
formulas and Haworth projection formulas (use whole chemical name for each
monosaccharide describing type of anomer and type of ring).
Structure of sedoheptulose
Aldonic, uronic and aldaric acids formed by different type oxidations of
monosaccharides (glucose and galactose).
Reduction products of glucose and mannose (alditols)
Reaction of lactone formation (gluconolactone)
Derivatives of monosaccharides: glucosamine, galactosamine, mannosamine,
N-acetylglucosamine and N-acetylgalactosamine
Phosphate ester of sugars: glyceraldehyde -3-phosphate; dihydroxyacetone-3phosphate; glucose-6-phosphate, glucose-1-phosphate; fructose 1,6 bisphosphate
Disaccharides: maltose and lactose and name them correctly using whole chemical
name. (You should be able to give the name of each disaccharide given its Haworth
structure).
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