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Carbohydrates
Carbohydrates are the most abundant biomolecules on Earth. Each year,
photosynthesis converts more than 100 billion metric tons of CO2 and H20 into
cellulose and other plant products. Carbohydrates are polyhydroxy aldehydes
and ketones, or substances that yield such compounds on hydrolysis. Many,
but not all have the empirical formula (CH2O)n, but some also contain
nitrogen, phosphorus, or sulfur. Carbohydrates occur in four main size
classes: monosaccharides, disaccharides, oligosaccharides, and
polysaccharides. The most abundant monosaccharide in nature is D-glucose,
which is also known as dextrose. A common disaccharide, sucrose, consists of
the six-carbon sugars D-glucose and D-fructose. Common polysaccharides
include cellulose and starches. Both of these are homopolymers of D-glucose
units, but with different linkages between residues. More complex
carbohydrate polymers attached to a protein or lipid moiety (glycoconjugates)
are also prevalent in nature.
Common Monosaccharides
Common aldoses and ketoses of three-, five-, and six-carbon
lengths are shown in Fig. 1. The simplest monosaccharides are
the two three-carbon trioses: D-glyceraldehyde, an aldotriose;
and dihydroxyacetone, a ketotriose. The most common
monosaccharides in nature are the aldohexose D-glucose, and the
ketohexose D-fructose. The aldopentoses D-ribose and 2-deoxyD-ribose are components of nucleotides and nucleic acids.
D & L Stereoisomers
All of the monosaccharides except dihydroxyacetone
contain one or more asymmetric (chiral) carbon
atoms and thus occur in optically active isomeric
forms. The simplest aldose, glyceraldehyde, contains
one chiral center (the middle carbon atom) and
therefore has two different optical isomers, or
enantiomers (Fig. -2). One of the two enantiomers of
glyceraldehyde is, by convention, designated the D
isomer and the other is the L isomer. In general, a
molecule with n chiral centers can have 2n
stereoisomers. Glyceraldehyde has 21 = 2; the
aldohexoses with four chiral centers have 24 = 16.
The stereoisomers of monosaccharides of each
carbon-chain length are divided into two groups
that differ in the configuration about the chiral
carbon that is most distant from the carbonyl
carbon. Those in which the configuration of this
reference carbon is the same as that of Dglyceraldehyde are designated D isomers. Those
with the same configuration as L-glyceraldehyde are
L isomers. Thus of the 16 possible aldohexoses, eight
are D forms and 8 are L forms. The reason D forms
predominate in nature is unknown.
Structures of the D Monosaccharides
The structures of the D stereoisomers of all the aldoses and ketoses having
three to six carbon atoms are shown in Fig. 3 (next two slides). The carbons of
a sugar are numbered beginning at the end of the chain nearest the carbonyl
group. Each of the eight aldohexoses, which differ in the stereochemistry at C2, C-3, and C-4, has its own name: D-glucose, D-mannose, D-galactose, and so
forth. The four- and five-carbon ketoses are designated by inserting “ul” into
the name of the corresponding aldose; for example, D-ribulose is the
ketopentose corresponding to the aldopentose D-ribose. The ketohexoses are
named otherwise: for example, fructose is named from the Latin fructus,
“fruit”.
Structures of the D-Aldoses
Structures of the D-Ketoses
Epimers of D-Aldohexoses
Two monosaccharides that differ only in the configuration around one chiral
carbon atom are called epimers. D-glucose and D-mannose are epimers
which differ in the configuration at C-2. D-glucose and D-galactose are
epimers that differ in the configuration at C-4 (Fig. 7-4).
Common L Stereoisomers
Some sugars occur naturally in their L form. Some examples are
L-arabinose (below) and the L isomers of some sugar derivatives
that are common components of glycoconjugates.
It is important to specify the enantiomers of carbohydrates in
a simple way. Suppose you had a model of one of these glucose
enantiomers in your hand. You could, of course, use the R,S
system to describe the configuration of one or more of the
asymmetric carbon atoms. A different system, however, was in
use long before the R,S system was established. The D,L system,
which came from proposals made in 1906 by M. A. Rosanoff, is
used for this purpose.
Often the designations aldo- and keto- are omitted, and these
molecules are referred to simply as trioses, tetroses, and the like.
C. Fischer Projection Formulas:
Glyceraldehydes contains a chiral center and therefore
exists as a pair of enantiomers.
Glyceraldehyde is a common name; the IUPAC name for this
monosaccharide is 2,3-dihydroxypropanal. Similarly, dihydroxyacetone
is a common name; its IUPAC name is 1,3-dihydroxypropanone. The
common names for these and other monosaccharides, however, are so
firmly rooted in the literature of organic chemistry and biochemistry
that they are used almost exclusively to refer to these compounds.
Therefore, throughout our discussions of the chemistry and
biochemistry of carbohydrates, we use the names most common in the
literature of chemistry and biochemistry.
CHO
CHO
H
C
OH
CH2OH
(R)-Glyceraldehyde
HO
C
H
CH2OH
(S)-Glyceraldehyde
Chemists
commonly
use
two-dimensional
representations called Fischer projections to show the
configuration of carbohydrates. Following is an illustration of
how a three-dimensional representation is converted to a
Fischer projection.
1
1
4
C
3
2
(S)
4
C
2
3
(R)
The horizontal segments of a Fischer projection represent bonds directed toward
you and the vertical segments represent bonds directed away from you. The only
atom in the plane of the paper is the chiral center.
Four Diastereomeric C5H10O5 Aldopentoses
CHO
CHO
CHO
H
OH
HO
H
OH
H
OH
HO
H
OH
H
OH
H
CH2OH
H
H
CH2OH
D-(-)-ribose
(2R,3R,4R)
CHO
OH
HO
H
H
HO
H
OH
H
CH2OH
CH2OH
D-(+)-xylose
(2R,3S,4R)
D-(-)-arabinose
(2S,3R,4R)
OH
D-(-)-lyxose
(2S,3S,4R)
CHO
CHO
H
OH
H
OH
HO
OH
H2
C
CH2OH
HO
O
OH
H
H
OH
H
OH
OH
HO
HO
D-(-)-Threose
CHO
OH
OH
CH2OH
H
D-(-)-Erythrose
H
H
5
C
H2
4
OH
3
OH
CH2OH
D-(-)-Ribose
2(R),3(R),4(R),5-tetrahydroxypentanal
1
2
H
O
H2
C
OH
O
OH
H
Formation of Hemiacetals and Hemiketals
Aldotetroses and all monosaccharides with five or more carbon atoms occur
predominantly as cyclic ring structures in which the carbonyl group has
formed a covalent bond with the oxygen of a hydroxyl group along the chain.
The formation of these ring structures is the result of a general reaction
between alcohols and aldehydes or ketones to form derivatives called
hemiacetals or hemiketals (Fig. 5). Actually, two molecules of an alcohol can
add to a carbonyl carbon. The product of the first reaction for an aldose is a
hemiacetal, and the product of the first reaction for a ketose is a hemiketal. If
the -OH and carbonyl groups are from the same molecule, a five- or sixmembered ring results. The addition of the second alcohol molecule produces
the full acetal or ketal, and the bond formed is a glycosidic linkage. When the
two reacting molecules are both monosaccharides, the acetal or ketal
produced is a disaccharide.
Fig. 5
Cyclization of D-Glucose
The reaction of the first alcohol with an aldose
or ketose creates an additional chiral center at
what was the carbonyl carbon. Because the
alcohol can add to the carbonyl carbon by
attacking either from the “front” or the
“back”, the reaction can produce either of two
stereoisomeric configurations, denoted  and
ß. For example, D-glucose (Fig. 7-6) exists in
solution as an intramolecular hemiacetal in
which the free hydroxyl group at C-5 has
reacted with the aldehyde C-1, rendering the
latter carbon asymmetric and producing two
possible stereoisomers, designated  and ß.
These two isomeric forms, which differ only in
their configuration about the hemiacetal
carbon atom are called anomers, and the
carbonyl carbon is called the anomeric
carbon. The same
nomenclature is used to describe anomeric forms of hemiketals such as formed
by fructose (see below). The  and ß anomers of D-glucose interconvert via the
linear form in aqueous solution by a process called mutarotation. In solution,
an equilibrium mixture forms which consists of about one-third -Dglucopyranose, two-thirds ß-D-glucopyranose, and trace amounts of the linear
and five-membered glucofuranose ring forms.
Pyranoses and Furanoses
Six-membered monosaccharide ring
compounds are called pyranoses because
they resemble pyran (Fig. -7). Fivemembered monosaccharide ring compounds
are called furanoses because they resemble
furan. The systematic names for the two ring
forms of D-glucose are therefore -Dglucopyranose and ß-D-glucopyranose.
Ketohexoses such as fructose also occur as
cyclic compounds with  and ß anomeric
forms. In these compounds the hydroxyl
group at C-5 (or C-6) reacts with the keto
group at C-2 forming a furanose (or
pyranose, not shown) ring containing a
hemiketal linkage. D-fructose readily forms a
furanose ring (Fig. 7-7). The more common
anomer of this sugar in combined forms or in
derivatives is ß-D-fructofuranose.
• Anomeric carbon is the new asymmetric carbon (C-1 in glucose) that is created by
cyclization at the carbon bound to oxygen in hemiacetal formation, with essential role
in reducing properties of glucides.
a. If the hydroxyl on the anomeric carbon is below the plane of the
ring, it is in
the α position.
b. If the hydroxyl on the anomeric carbon is above the plane of the
ring, it is in
the β position.
CH2 -OH
CH2-OH
O
H
H
OH
H
H
OH
H
OH
OH
H
O
H
OH
OH
H
H
OH
H
OH
Mutarotation is the process by which α and β sugars, in solution, slowly
change into an equilibrated mixture of both.
1. α-D-Glucopyranose (62%);
2. β-D-Glucopyranose (38%);
3. α-D-Glucofuranose (trace);
4. β-D-Glucofuranose (trace);
5. Linear D-Glucose (0.01%).
GLUCOSE
CH2 -OH
CH2-OH
O
H
H
OH
H
CHO
H
C OH
HO C
H
C OH
H
C OH
OH
CH2 OH
H
H
OH
β-D-glucopyranose
CH2 -OH
H
O
CH-OH
H
OH
OH
OH
H
H
H
CH2 -OH
OH
OH
OH
OH
α-D-glucopyranose
CH-OH
H
OH
H
H
OH
O
H
OH
α-D-glucofuranose
OH
O
H
OH
H
H
OH
β-D-glucofuranose
CHO
H
C OH
HO C
H
HO C
H
H
C OH
CH2 OH
GALACTOSE
CH2-OH
O
OH
H
OH
CHO
H
C OH
HO C
H
HO C
H
H
C OH
CH2 OH
H
H
OH
H
H
OH
α-galactopyranose
CH2-OH
O
OH
H
OH
OH
H
H
H
H
OH
β-galactopyranose
FRUCTOSE
CH2-OH
H
CH2 -OH
C
O
HO C
H
H
C
OH
H
C
OH
CH2 OH
CH2-OH
O
OH
H
OH
H
OH
α-fructofuranose
CH2-OH
H
OH
O
OH
H
OH
H
CH2-OH
β-fructofuranose
Fisher Projection & Haworth Perspective
Formulas
Cyclic sugar structures are more accurately represented in Haworth
perspective formulas (see below) than in Fischer projections used for linear
sugar structures. In Haworth formulas the six-membered ring is tilted to
make its plane almost perpendicular to that of the paper. The bonds closest
to the reader are drawn thicker than those farther away. To convert the
Fisher projection formula of any linear D-hexose to a Haworth perspective
formula, draw the six-membered ring (five carbons, and one oxygen at the
upper right), number the carbons in a clockwise direction beginning with
the anomeric carbon, then add the hydroxyl groups as follows. If a hydroxyl
group is to the right in the Fischer formula, it is placed pointing down in the
Haworth formula. If a hydroxyl group is to the left in the Fischer formula,
then it is placed pointing up in the Haworth
formula. The terminal -CH2OH group
projects upward for the D-enantiomer, and
downward for the L-enantiomer. When the
hydroxyl group on the anomeric carbon of a
D-hexose is on the same side of the ring as C6, the structure is by definition ß. When it is
on the opposite side from C-6, the structure is
.
Example 1. Conversion of Fisher Projection to
Haworth Perspective Formulas
Conformational Formulas of Pyranoses
It is important to keep in mind the actual
conformational structures of the ring forms of
monosaccharides. For example the sixmembered pyranose ring is not actually planar,
as suggested by Haworth representations, but
instead tends to assume either of two chair
conformations (Fig. 7-8). The interconversion
of the two chair forms (conformers) does not
require bond breakage and does not change
the configurations of substituents attached to
any of the ring carbons. However, it does
require a considerable input of energy. The
actual three-dimensional structures of
monosaccharide units are important in
determining the biological properties and
functions of some polysaccharides, as shown
below.
CARBOHYDRATES
WITH IMPORTANCE IN
MEDICINE AND PHARMACY
TRIOSES
HC
H
C
O
CH2OH
OH
C
CH2OH
glyceraldehyde
O
CH2OH
dihydroxyacetone
• Result as intermediary metabolites (in phosphoric esters form) in the
reactions of carbohydrate degradation (glycolysis)
PENTOSES
CHO
H
C OH
H
C OH
H
C OH
CH2OH
CH2-OH
O
H
H
H
H
OH
CHO
OH
OH
H
C H
H
C OH
H
C OH
CH2OH
β-D-ribose
CH2-OH
OH
O
H
H
H
H
OH
H
β-2-deoxy-D-ribose
• Exogenous origin (food)
• In the cell, have higher metabolic stability than hexoses
• D-ribose (anomer β):
• Does not exist free in the cell
• Biological importance: as phosphate ester enters in the structure of
nucleosides, nucleotides, RNA, coenzymes, metabolic intermediates in
pentose-phosphate cycle
• 2-Deoxy-D-ribose (anomer β)
• In the structure of deoxyribonucleosides and nucleotides, structural
monomers of deoxyribonucleic acid (DNA)
HEXOSES
• Aldohexoses
• glucose = Glc = G (dextrose, blood sugar, grape sugar),
• galactose = Gal (cerebrose),
• mannose = Man
• Ketohexose
• fructose = Fru, F (levulose, fruit sugar )
GLUCOSE (GLC, G)
•
Ubiquitous in the animal and plant organisms
•
The main ose in the human organism
•
Location
•
In all the cells and fluids of the organism
except the urine
CH2 -OH
CHO
H
C OH
HO C
H
OH
H
H
C OH
H
C OH
O
H
H
H
OH
OH
H
OH
CH2 OH
In the blood it exists in a constant interval of 65-110 mg/dl (glycemia);
maintained mainly by the antagonistic action of 2 pancreatic hormones:
•insulin - hypoglicemiant
•glucagon – hyperglycemiant
The increased values of glycemia are present in diabetes mellitus and
endocrine diseases
Functions
-
– energetic: through degradation (glycolysis) energy is generated as ATP
– it enters in the structure of
diglucides: maltose, isomaltose, lactose, sucrose, celobiose
polyglucides: starch, glycogen, cellulose
– by oxidation in the liver it is transformed in glucuronic acid with important role in
detoxifying the organism.
CH2-OH
CHO
GALACTOSE (GAL)
H
C OH
HO C
H
HO C
H
H
O
OH
H
OH
OH
H
H
H
H
OH
C OH
CH2 OH
Location: it exists in reduced amount in blood, CSF, urine
Function:
– With glucose forms lactose, the sugar in the milk
– Enters in the structure of complex lipids in the brain (cerebrosides,
sulfatides, gangliosides)
–By oxydation in the liver forms the galacturonic acid that enters in the
structure of mucopolyglucides (complex carbohydrates)
CH2 -OH CH2-OH
FRUCTOSE (FRU, F)
• The sweetest of all sugars
• Structure: ketohexose
C
O
HO C
H
H
C
OH
H
C
OH
H
CH2-OH
O
OH
H
OH
OH
H
CH2 OH
• pyranose in free form and
• furanose in all natural derivatives
• Location:
• free in the secretion of seminal vesicles
• combined with glucose forms the sucrose, the sugar in the
fruits
• as phosphoric ester is an intermediate in the metabolism
of glucose (glycolysis and pentose-phosphate cycle),
Important Hexose Derivatives (I)
In addition to simple hexoses such as glucose, galactose, and mannose, there
are many sugar derivatives in which a hydroxyl group in the parent
compound is replaced with another substituent, or a carbon atom is oxidized
to a carboxyl group. In addition, hexoses in metabolic pathways commonly
are phosphorylated on hydroxyl groups (Fig. 7-9).
Important Hexose Derivatives (II)
In amino sugars, an -NH2 group replaces one of the -OH groups in
the parent hexose. Substitution of -H for -OH produces a deoxy
sugar, some of which occur in nature as L isomers. The acidic sugars
contain a carboxylate group, which confers a negative charge at
neutral pH. Lactones result from the formation of an ester linkage
between the C-1 carboxylate group and the C-5 hydroxyl group of
the sugar. Some notable functions of hexose derivatives in biology
are 1) N-acetylglucosamine and N-acetylmuramic acid, components
of the bacterial cell wall; and 2) N-acetylneuraminic acid (sialic
acid) and fucose, components of the oligosaccharide chains of
mammalian glycoproteins.
Sugar derivatives
CHO
COOH
CH2OH
H
C
OH
H
C
OH
H
C
OH
CH2OH
D-ribitol
H
C
OH
HO
C
H
OH
H
C
OH
OH
H
C
OH
H
C
OH
HO
C
H
H
C
H
C
CH2OH
D-gluconic acid
COOH
D-glucuronic acid
 sugar alcohol - lacks an aldehyde or ketone; e.g., ribitol.
 sugar acid - the aldehyde at C1, or OH at C6, is oxidized
to a carboxylic acid; e.g., gluconic acid, glucuronic acid.
Sugar derivatives
CH2OH
CH2OH
O
H
H
OH
H
H
OH
H
OH
OH
H
NH2
-D-glucosamine
O
H
H
H
O OH
OH
H
N
C
CH3
H
-D-N-acetylglucosamine
amino sugar - an amino group substitutes for a hydroxyl.
An example is glucosamine.
The amino group may be acetylated, as in
N-acetylglucosamine.
H
O
H3C
C
O
NH
R
H
COO
H
R=
OH
H
HC
OH
HC
OH
CH2OH
OH
H
N-acetylneuraminate (sialic acid)
N-acetylneuraminate (N-acetylneuraminic acid, 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, as shown here.
Disaccharides (I)
A disaccharide (e.g., maltose, Fig. 7-10) is
formed from two monosaccharides (two Dglucose molecules for maltose) when an -OH
alcohol group of the right D-glucose condenses
with the intramolecular hemiacetal of the left
D-glucose. Water is eliminated, and a glycoside
with a glycosidic bond is formed. The reversal
of this reaction is hydrolysis by attack of a
water molecule on this bond--a reaction which
is readily catalyzed using dilute acid. The
oxidation of a sugar by cupric ion occurs only
with its linear form, which exists in equilibrium
with its cyclic
forms. Thus, the anomeric carbon of the D-glucose residue on the left can no
longer react with Cu2+ because it is tied up in a glycosidic bond. In contrast, the
hemiacetal linkage in the right D-glucose molecule can open up, and react with
Cu2+. For this reason, the right end of maltose is called its reducing end. Because
mutarotation interconverts the  and ß forms of the right hemiacetal linkage, the
bonds at this position are sometimes depicted with wavy lines to indicate that
either configuration at the anomeric carbon is possible. In maltose, the
configuration of the anomeric carbon atom in the glycosidic linkage is .
Disaccharides (II)
The convention for formally naming disaccharides (and oligosaccharides) is as
follows. 1) Start with the configuration ( or ß) at the anomeric carbon joining the
first monosaccharide unit (on the left) to the second. 2) Name the nonreducing
residue at the left; to distinguish five- and six-membered ring structures, insert
“furano” or “pyrano” into the name. 3) Indicate in parentheses the two carbon
atoms joined by the glycosidic bond, with an arrow connecting the two numbers.
In maltose, (14) shows that C-1 of the first D-glucose unit is joined to C-4 of the
second. 4) Name the second residue. Following this convention, maltose is -Dglucopyranosyl-(14)-D-glucopyranose. Because most sugars in the textbook are
the D enantiomers and the pyranose form of hexoses predominates, a shortened
version of the formal name of compounds, such as maltose, can be used which
gives the configuration of the anomeric carbon and names the carbons joined by
the glycosidic bond. In this abbreviated nomenclature, maltose is Glc(14)Glc.
Symbols and abbreviations for common monosaccharides and some of their
derivatives are listed in Table 7-1 (not covered).