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Essential Biochemistry
Supplement on Carbohydrates
Of the major molecular building blocks of cells—nucleotides, amino acids, and lipids—
carbohydrates are the most abundant. Although their atomic composition is largely limited to C, H,
and O, carbohydrates take on a variety of biological functions from energy metabolism to cellular
structure. Carbohydrates, also known as sugars or saccharides, occur as monosaccharides
(simple sugars), small polymers (disaccharides, trisaccharides, and so on), and larger
polysaccharides (sometimes called complex carbohydrates). Monosaccharides follow the
molecular formula (CH2O)n, where n ≥ 3 (hence the name carbohydrate). But even saccharide
derivatives—many of which include groups containing nitrogen, phosphorus, and other
elements—are easy to recognize by their large number of hydroxyl (—OH) groups. This section
surveys monosaccharides and their derivatives, some common disaccharides, and polysaccharides.
1. MONOSACCHARIDES
The simplest sugars are the three-carbon compounds glyceraldehyde and dihydroxyacetone:
A sugar such as glyceraldehyde, in which the carbonyl group is an aldehyde, is known as an
aldose, and a carbohydrate such as dihydroxyacetone, in which the carbonyl group is a ketone, is
known as a ketose. In most ketoses, the carbonyl group occurs at the second carbon (C2).
Monosaccharides can also be described according to the number of carbon atoms they contain;
for example, the three-carbon compounds shown above are trioses. Tetroses contain four
carbons, pentoses five, hexoses six, and so on.
The aldopentose ribose (below) is a component of ribonucleic acid (RNA; its derivative 2′deoxyribose occurs in deoxyribonucleic acid, DNA). By far the most abundant monosaccharide
is glucose, an aldohexose. A common ketohexose is fructose:
Most carbohydrates are chiral compounds
Note that glucose, shown above, is a chiral compound because several of its carbon atoms (all
except C1 and C6) bear four different substituents (see Box 4-4 for a discussion of chirality). As
a result, glucose has a number of stereoisomers, as do nearly all monosaccharides (the symmetric
dihydroxyacetone is one exception). Below we describe several types of stereoisomerism that
apply to carbohydrates.
a. D and L enantiomers
Like the amino acids (Box 4-4), glyceraldehyde has two different structures that exhibit mirror
symmetry. Such pairs of structures, known as enantiomers, cannot be superimposed by rotation.
By convention, these structures are given the designations L and D, derived from the Greek levo,
left and dextro, right.
The enantiomeric forms of larger monosaccharides are given the D or L designation by
comparing their structures to D- and L-glyceraldehyde. In a D sugar, the asymmetric carbon
farthest from the carbonyl group (that would be C5 in glucose) has the same spatial arrangement
as the chiral carbon of D-glyceraldehyde. In an L sugar, that carbon has the same arrangement as
in L-glyceraldehyde. Thus, every D sugar is the mirror image of an L sugar.
Although enantiomers behave identically in a strictly chemical sense, they are not biologically
equivalent. This is because biological systems, which are built of other chiral compounds, such
as L-amino acids, can distinguish D and L sugars. Most naturally occurring sugars have the D
configuration, so the D and L prefixes are often omitted from their names.
b. Epimers
Glucose, in addition to its enantiomeric carbon (C1), has four other asymmetric carbons, so there
are stereoisomers for the configuration at each of these positions. Carbohydrates that differ in
configuration at one of these carbons are known as epimers. For example, the common
monosaccharide galactose is an epimer of glucose, at position C4:
Both ketoses and aldoses have epimeric forms. And like enantiomers, epimers are not
biologically interchangeable: an enzyme whose active site accommodates glucose may not
recognize galactose at all.
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c. α and β Anomers
The numerous hydroxyl groups that characterize carbohydrate structures also provide multiple
points for chemical reactions to occur. One such reaction is an intramolecular rearrangement in
which the sugar’s carbonyl group reacts with one of its —OH groups to form a cyclic structure:
The cyclic sugars are represented as Haworth projections in which the darker horizontal lines
correspond to bonds above the plane of the paper, and the lighter lines correspond to bonds
behind the plane of the paper. A simple rule makes is easy to convert a structure from its linear
Fischer projection (in which horizontal bonds are above the plane of the paper and vertical
bonds are behind it) to a Haworth projection: groups projecting to the right in a Fischer projection will point down in a Haworth projection, and groups projecting to the left will point up.
As a result of the cyclization reaction, the hydroxyl group attached to what was the carbonyl
carbon (C1 in the case of glucose) may point either up or down. In the α anomer, this hydroxyl
group lies on the opposite side of the ring from the CH2OH group of the chiral carbon that
determines the D or L configuration (in the α anomer of glucose above, the hydroxyl group points
down). In the β anomer, the hydroxyl group lies of the same side of the ring as the CH2OH
group of the chiral carbon that determines the D or L configuration (up in the glucose molecule
shown above).
Unlike enantiomers and epimers, which are not interchangeable, anomers in an aqueous solution
freely interconvert between the α and β forms, unless the hydroxyl group attached to the
anomeric carbon is linked to another molecule. In fact, a solution of glucose molecules consists
of about 64% β anomer, about 36% α anomer, and only trace amounts of the linear or openchain form.
2. MONOSACCHARIDE DERIVATIVES
The anomeric carbon of a monosaccharide is easy to recognize: it is the carbonyl carbon in the
straight-chain form of the sugar, and it is the carbon bonded to both the ring oxygen and a
hydroxyl group in the cyclic form of the sugar. The anomeric carbon can undergo oxidation, so it
can reduce substances such as Cu(II) to Cu(I). This chemical reactivity, often assayed using a
copper-containing solution known as Benedict’s reagent, can distinguish a free monosaccharide,
called a reducing sugar, from a monosaccharide in which the anomeric carbon has already
reacted with another molecule. For example, when a glucose molecule (a reducing sugar) reacts
with methanol (CH3OH), the result is a nonreducing sugar:
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Note that because the anomeric carbon is involved in the reaction, the methyl group can end up
in either the α or β position. The bond that links the anomeric carbon to the other group is called
a glycosidic bond, and a molecule consisting of a sugar linked to another molecule is called a
glycoside. Glycosidic bonds link the monomers in oligo- and polysaccharides (see below) and
also link the ribose groups to the purine and pyrimidine bases of nucleotides (Section 3-1).
Phosphorylated sugars, including glyceraldehyde 3-phosphate and fructose-6-phosphate, appear
as intermediates in the metabolic pathways for breaking down glucose (glycolysis; Section 10-2)
and synthesizing it (photosynthesis; Section 13-3).
Other metabolic processes replace a hydroxyl group with an amino group to produce an amino
sugar, such as glucosamine:
Oxidation of a sugar’s carbonyl and hydroxyl groups can yield sugars containing carboxylic acid
groups, and reduction can yield molecules such as xylitol, a sweetener used in “sugarless” foods:
One metabolically essential carbohydrate-modifying reaction is the one catalyzed by
ribonucleotide reductase, in which ribonucleotides (NDP) are converted to deoxyribonucleotides
(dNDP) for DNA synthesis (Box 15-B):
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3. DISACCHARIDES AND OLIGOSACCHARIDES
When a glycosidic bond links two monosaccharides, the result is a disaccharide. In nature,
disaccharides occur as intermediates in the digestion of polysaccharides and as a source of
metabolic fuel. For example, lactose, secreted into the milk of lactating mammals, consists of
galactose and glucose:
Note that the anomeric carbon (C1) of galactose is linked to C4 of glucose via a β-glycosidic
bond. If the two sugars were linked by an α-glycosidic bond, or if the galactose anomeric carbon
were linked to a different glucose carbon, the result would be an entirely different disaccharide.
The enzymes that catalyze the condensation (linkage) of two monosaccharides or the hydrolysis
(breakage) of a disaccharide are highly specific for the identities of the monosaccharide units and
the particular groups that are involved in the glycosidic bond. Lactose serves as a major food for
newborn mammals. Most adult mammals, including humans, produce very little lactase (also
called β-galactosidase), the enzyme that breaks the glycosidic bond of lactose, and therefore
cannot efficiently digest this disaccharide.
Sucrose, or table sugar, is the most abundant disaccharide in nature:
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In this molecule, the anomeric carbon of glucose (in the α configuration) is linked to the
anomeric carbon of fructose (in the β configuration). Sucrose is the major form in which newly
synthesized carbohydrates are transported from a plant’s leaves, where most photosynthesis
occurs, to other plant tissues to be used as a fuel or stored as starch for later use.
Glycoproteins Contain Oligosaccharide Chains
Because there are so many different monosaccharides—considering all possible stereoisomers
and their chemical derivatives—and so many ways in which the monosaccharides can be linked,
the number of possible structures for oligosaccharides of even just a few residues is enormous.
Organisms take advantage of this complexity to mark various structures—mainly proteins and
lipids—with unique oligosaccharides. The familiar A, B, and O blood types, for example, are
determined by the presence of different oligosaccharides on the surface of red blood cells (see
Box 8-B).
Most of the proteins that are secreted from eukaryotic cells or remain on their surface are
glycoproteins (see Section 8-2) in which one or more oligosaccharide chains are covalently
attached to the polypeptide chain shortly after its synthesis. Although some of these
oligosaccharide groups share a common core structure of mannose and glucose derivatives, a
plethora of enzymes that add and remove various monosaccharides can generate a variety of
different oligosaccharides whose biological functions are not all understood.
Some oligosaccharide groups constitute a sort of intracellular addressing system so that newly
synthesized proteins will be delivered to their proper cellular location, such as a lysosome. In
some cases, a thick coating of oligosaccharide groups appears to enhance the stability of proteins
in the relatively harsh extracellular environment. In other cases, the oligosaccharide groups serve
as recognition and attachment points for interactions between different types of cells. For
example, circulating white blood cells latch onto oligosaccharides on the cells lining the blood
vessels in order to leave the bloodstream and migrate to sites of injury or infection.
4. POLYSACCHARIDES
Most polysaccharides, some of which are truly enormous molecules, generally do not exhibit the
heterogeneity and complexity of oligosaccharides. Instead they tend to consist of one or a pair of
monosaccharides that are linked over and over in the same fashion. However, this sort of
structural homogeneity is well-suited to the function of polysaccharides as fuel storage molecules
and architectural elements.
Starch and Glycogen Are Fuel Storage Molecules
Starch and glycogen are polymers of glucose residues linked by glycosidic bonds designated
α(1→4); in other words, the anomeric carbon (carbon 1) of one residue is linked by an αglycosidic bond to carbon 4 of the next residue:
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Plants manufacture a linear form of starch, called amylose, which can consist of several thousand
glucose residues. Amylopectin, an even larger molecule, includes α(1→6) glycosidic linkages
every 24 to 30 glucose residues, so that it is a branched polymer:
Compiling many monosaccharide residues in a single polysaccharide is an efficient way to store
glucose, the plant’s primary metabolic fuel. The α-linked chains curve into helices so that the
entire molecule forms a relatively compact particle:
Animals store glucose in the form of glycogen, a polymer that resembles amylopectin but with
branches every 12 residues or so. Due to its highly branched structure, a glycogen molecule can
be quickly assembled or disassembled according to the metabolic needs of the cell, because the
enzymes that add or remove glucose residues work from the ends of the branches.
Cellulose and Chitin Are Structural Molecules
Cellulose, like amylose, is a linear polymer containing thousands of glucose residues. However,
the residues are linked by β(1→4) rather than α(1→4) glycosidic bonds:
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This simple difference in bonding has profound structural consequences: whereas starch
molecules form compact granules inside the cell, cellulose forms extended fibers that lend
rigidity and strength to plant cell walls. Individual cellulose polymers form bundles with
extensive hydrogen bonding (dashed lines) within and between adjacent chains:
Animals do not synthesize cellulose, and most cannot digest it. Organisms such as termites and
ruminants, who do derive energy from cellulose-rich foods, harbor bacteria that produce
cellulases capable of hydrolyzing the β(1→4) bonds between glucose residues.
The exoskeletons of insects and crustaceans and the cell walls of many fungi contain a celluloselike polymer called chitin, in which the β(1→4)-linked residues are the glucose derivative Nacetylglucosamine:
Bacterial Cell Walls Contain Peptidoglycan
The cell membranes of bacteria are surrounded by a rigid but porous cell wall that determines the
overall shape of the cell. In the so-called Gram-positive bacteria, the cell wall takes up the violet
Gram stain; in Gram-negative bacteria, an additional outer membrane prevents the stain from
reaching the cell wall. The cell wall is made of peptidoglycan, a cross-linked network of
peptides and oligosaccharides. The carbohydrate component in many species is a repeating
β(1→4)-linked disaccharide:
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Four- and five-residue peptides cross-link the saccharide chains to form a honeycomb-like
structure as thick as 250 Å in some Gram-positive species. Antibiotics of the penicillin family
block the formation of the peptide cross-links, thereby weakening the cell wall and causing the
cell to burst.
Glycosaminoglycans Function as Space-Fillers and Shock-Absorbers
A variety of extracellular polysaccharides are produced by both eukaryotes and prokaryotes.
Animal tissues contain long saccharide chains, called glycosaminoglycans, that may be
covalently linked to proteins to form enormous branched aggregates called proteoglycans.
Glycosaminoglycans are typically built from repeating disaccharides studded with carboxylate
and sulfate groups in addition to the usual hydroxyl groups. Chondroitin sulfate chains, for
example,
which are found in cartilage and other connective tissue, contain hundreds of disaccharide units.
The many hydrophilic groups attract water molecules, so glycosaminoglycans are highly
hydrated and occupy the spaces between cells and other components of the extracellular matrix,
such as collagen fibrils (Section 5-6). Under mechanical pressure, some of the water can be
squeezed out of the glycosaminoglycans, which allows connective tissue and other structures to
accommodate the body’s movements. Pressure also brings the negatively charged groups of the
polysaccharides close together. When the pressure abates, the glycosaminoglycans quickly
spring back to their original shape as the repulsion between anionic groups is relieved and water
is drawn back into the molecule. This sponge-like action of glycosaminoglycans in the spaces of
the joints provides shock absorption.
Glycosaminoglycans also act as lubricants for the body’s moving parts. In the absence of stress,
the polysaccharide chains are somewhat tangled together and form a highly viscous material.
Under stress, the chains tend to align, which reduces their viscosity and leads to a more fluid
state.
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PROBLEMS
1.
Glucose can be described as an aldohexose. Use similar terminology to describe the
following sugars:
(a)
(b)
2.
Which of the following are isomers of glucose?
glucose-6-phosphate, fructose, galactose, ribose
3.
Mannose is the C2 epimer of glucose Draw its structure.
4.
An enzyme recognizes only the α anomer of glucose as a substrate and converts it to
product. If the enzyme is added to a mixture of the α and β anomers, explain why all the
sugar molecules in the sample will eventually be converted to product.
5.
Draw the ketose whose reduction would yield xylitol.
6.
Explain why lactose is a reducing sugar, whereas sucrose is not.
7.
Instead of starch, some plants produce inulin, which is a polymer of β(2→1)-linked
fructose residues. Draw the structure of an inulin disaccharide.
8.
Calculate the net charge of a chondroitin sulfate molecule containing 100 disaccharide
units.
9.
In a homopolymer, all the monomers are the same, and in a heteropolymer, the
monomers are different. Which of the polysaccharides discussed here are homopolymers
and which are heteropolymers?
10.
Identify the parent monosaccharides in the disaccharide unit of chondroitin sulfate.
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SOLUTIONS TO PROBLEMS
1.
(a) aldotetrose (threose); (b) ketopentose (ribulose)
2.
Fructose and galactose are isomers of glucose.
3.
4.
All the sugar molecules will be converted to product because the α and β anomers are in
equilibrium. Depletion of molecules in the α form will cause more of the β anomers to
convert to α anomers, which will then be converted to product.
5.
6.
Lactose is a reducing sugar because it has a free anomeric carbon (C1 of the glucose
residue). Sucrose is not a reducing sugar because the anomeric carbons of both glucose
and fructose are involved in the glycosidic bond.
7.
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8.
Each disaccharide unit of chondroitin sulfate has two negatively charged groups: a
carboxylate group and a sulfate group. One hundred of these disaccharide units would
yield a net charge of –200.
9.
Starch, glycogen, cellulose, and chitin are homopolymers. Peptidoglycan and chondroitin
sulfate are heteropolymers.
10.
The residue on the left is a glucose derivative in which C6 has been oxidized to a
carboxylic acid. The residue on the right is a galactose derivative in which C2 bears an
amino group and C4 bears a sulfate group.
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