I wou l d feel more opt i m istic about a bright future for man if he spent

less time prov i ng that he can outwit Nature and more time tasting her
sweetness and respecti ng her sen i o rity.

-E. B. White, "Coon Tree, " 1 977

Carbohydrates and Glycobiology

7.1 Monosaccharides and Disaccharides 235 Oligosaccharides consist of short chains of mono­

7.2 244
saccharide units, or residues, joined by characteristic
Polysaccharides linkages called glycosidic bonds. The most abundant are
7.3
the disaccharides, with two monosaccharide units.
Glycoconjugates: Proteoglycans, Glycoproteins,
252
Typical is sucrose (cane sugar), which consists of the
and Glycolipids
six-carbon sugars o-glucose and o-fructose. All common
7.4 Carbohydrates as Informational Molecules: monosaccharides and disaccharides have names ending
257
with the suffix "-ose." In cells, most oligosaccharides
The Sugar Code

7.5 263
consisting of three or more units do not occur as free en­
Working with Carbohydrates tities but are joined to nonsugar molecules (lipids or
proteins) in glycoconjugates.
The polysaccharides are sugar polymers contain­

C
arbohydrates are the most abundant biomolecules on ing more than 20 or so monosaccharide units; some have
Earth. Each year, photosynthesis converts more than hundreds or thousands of units. Some polysaccharides,
100 billion metric tons of C02 and H20 into cellulose such as cellulose, are linear chains; others, such as
and other plant products. Certain carbohydrates (sugar glycogen, are branched. Both glycogen and cellulose
and starch) are a dietary staple in most parts of the world, consist of recurring units of o-glucose, but they differ in
and the oxidation of carbohydrates is the central energy­ the type of glycosidic linkage and consequently have
yielding pathway in most nonphotosynthetic cells. Carbo­ strikingly different properties and biological roles.
hydrate polymers (also called glycans) serve as structural
and protective elements in the cell walls of bacteria and
7.1 Monosaccharides and Disaccharides
plants and in the connective tissues of animals. Other car­
bohydrate polymers lubricate skeletal joints and partici­ The simplest of the carbohydrates, the monosaccha­
pate in recognition and adhesion between cells. Complex rides, are either aldehydes or ketones with two or more
carbohydrate polymers covalently attached to proteins or hydroxyl groups; the six-carbon monosaccharides glu­
lipids act as signals that determine the intracellular loca­ cose and fructose have five hydroxyl groups. Many of the
tion or metabolic fate of these hybrid molecules, called gly­ carbon atoms to which hydroxyl groups are attached are
coconjugates. This chapter introduces the major classes chiral centers, which give rise to the many sugar
of carbohydrates and glycoconjugates and provides a few stereoisomers found in nature. We begin by describing
examples of their many structural and functional roles. the families of monosaccharides with backbones of
Carbohydrates are polyhydroxy aldehydes or ketones, three to seven carbons-their structure and stereoiso­
or substances that yield such compounds on hydrolysis. meric forms, and the means of representing their three­
Many, but not all, carbohydrates have the empirical formula dimensional structures on paper. We then discuss several
(CH20)n; some also contain nitrogen, phosphorus, or sulfur. chemical reactions of the carbonyl groups of monosac­
There are three major size classes of carbohydrates: charides. One such reaction, the addition of a hydroxyl
monosaccharides, oligosaccharides, and polysaccha­ group from within the same molecule, generates cyclic
rides (the word "saccharide" is derived from the Greek forms having four or more backbone carbons (the forms
sakcharon, meaning "sugar"). Monosaccharides, or that predominate in aqueous solution). This ring closure
simple sugars, consist of a single polyhydroxy aldehyde creates a new chiral center, adding further stereochemi­
or ketone unit. The most abundant monosaccharide in cal complexity to this class of compounds. The nomen­
nature is the six-carbon sugar o-glucose, sometimes re­ clature for unambiguously specifying the configuration

[ns]
ferred to as dextrose. Monosaccharides of four or more about each carbon atom in a cyclic form and the means
carbons tend to have cyclic structures. of representing these structures on paper are therefore
! 236l Carbohydrates a n d G l yco b i o l o g y
L �

I
H 0 H

"-, _f'
"-, ,f'
"-. 7'
c H-C-OH
c c
H 0 H 0
I I
I I I I
H H H-C-OH C=O
0
I
I
"- -1
I
c� H-C-OH HO-C-H HO-C-H H-C-OH CH2
I I I
I
I
I I I I
H-C-OH C=O H-C-OH H-C-OH H-C-OH H-C-OH
I
H-C-OH H-C-OH H-C-OH H-C-OH H-C-OH H-C-OH
I I I I I I
H H CH20H CH�H CH�H CH20H
n-Glyceraldehyde, Dihydroxyacetone, n-Glucose, n-Fructose, n-Ribose, 2-Deoxy-n-ribose,
an aldotriose a ketotriose an aldohexose a ketohexose an aldopentose an aldopentose
(a) (b) (c)

FIGURE 7-1 Representative monosaccharides. (a) Two trioses, an aldose

described in some detail; this information will be useful and a ketose. The carbonyl group in each is shaded. (b) Two common
as we discuss the metabolism of monosaccharides in Part hexoses. (c) The pentose components of nucleic acids. o-Ribose is a
II. We also introduce here some important monosaccha­ component of ribonucleic acid (RNA), and 2-deoxy-o-ribose is a com­
ride derivatives encountered in later chapters. ponent of deoxyribonucleic acid (DNA).

The Two Families of Monosaccharides Are AI doses

and Ketoses structures on paper, we often use Fischer projection
formulas (Fig. 7-2). In Fischer projection formulas,
Monosaccharides are colorless, crystalline solids that are horizontal bonds project out of the plane of the paper,
freely soluble in water but insoluble in nonpolar solvents. toward the reader; vertical bonds project behind the
Most have a sweet taste. The backbones of common mono­ plane of the paper, away from the reader.
saccharides are unbranched carbon chains in which all the
carbon atoms are linked by single bonds. In the open-chain
form, one of the carbon atoms is double-bonded to an oxy­
Mirror
gen atom to form a carbonyl group; each of the other car­
CHO
bon atoms has a hydroxyl group. If the carbonyl group is at
an end of the carbon chain (that is, in an aldehyde group)
the monosaccharide is an aldose; if the carbonyl group is
at any other position (in a ketone group) the monosaccha­
ride is a ketose. The simplest monosaccharides are the
two three-carbon trioses: glyceraldehyde, an aldotriose,
and dihydroxyacetone, a ketotriose (Fig. 7-la).
Monosaccharides with four, five, six, and seven car­
bon atoms in their backbones are called, respectively, tet­
roses, pentoses, hexoses, and heptoses. There are aldoses
and ketoses of each of these chain lengths: aldotetroses
and ketotetroses, aldopentoses and ketopentoses, and so Ball-and-stick models
on. The hexoses, which include the aldohexose n-glucose
I
CHO CHO
and the ketohexose D-fructose (Fig. 7-1 b), are the most I
I I
common monosaccharides in nature. The aldopentoses D­ H-C-OH HO-C-H
ribose and 2-deoxy-D-ribose (Fig. 7-1c) are components CH20H
CH20H
of nucleotides and nucleic acids (Chapter 8). n-Glyceraldehyde L-Glyceraldehyde

Monosaccharides Have Asymmetric Centers Fischer projection formulas

All the monosaccharides except dihydroxyacetone con­ CHO

6 -oH
CHO
r
tain one or more asymmetric ( chiral) carbon atoms and
Q- H
i
H- HO-
thus occur in optically active isomeric forms (pp. 1 6-1 7 ) . i !
The simplest aldose, glyceraldehyde, contains one chiral CH20H CH20H
center (the middle carbon atom) and therefore has two n-Glyceraldehyde L-Glyceraldehyde
different optical isomers, or enantiomers (Fig. 7-2) .
Perspective formulas

One of the two enantiomers is, by con­

KEY C O N V E N T I O N : FIGURE 7-2 Three ways to represent the two enantiomers of glycer­
vention, designated the D isomer, the other the 1 isomer. aldehyde. The enantiomers are mi rror images of each other. Bal l-and­
As for other biomolecules with chiral centers, the ab­ stick models show the actual configuration of molecules. Recall (see
solute configurations of sugars are known from x-ray Fig. 1 -1 7) that in perspective formulas, solid wedge-shaped bonds
crystallography. To represent three-dimensional sugar point toward the reader, dashed wedges point away.
 7 . 1 Monosaccha rides a n d Disaccha rides ["237]

\!0
Three carbons Four carbons Five carbon
H 0 H 0 H 0 H

?I
'- .of'

yI
,? "- ,?
c c

{
c

H c c H- C' -OH
H H

0
0 0
" ,? " ,? I r I I
HO-C-H H- C'-QH HQ-C-H

t
"- ,? I I I
HO- -H HO- -H

H-C'-OH
H- C-OH HO-C-H H-C-OH H- -DH
I I I I
H-C-QR

6H20H
H-C-OH H-C-OH H-C-OH H- �-QH H-C-OH
I I I I I

I o-Glyceraldehyde I I o-Erythrose I I I I D-Arabino ej I I

CR20H CH20H CH20H CH20H CH20H H20H

D-Threose o- Ribose o-Xylose o-Lyxose

Six carbons

c c c c c c c c
H 0 H 0 H 0 H 0 H 0 H 0 H 0 H 0
" ,? "- ,? " ,? " ,? " ,? " ,? " ,? "- ,?

I I I I I I I I
H-C-OH HO-C-H H-C-OH HO-C-H H-C-OH HO-C-H H-C-OH HO-C-H
I I I I I I I I
H-C-OH H-C-OH HO-C-H HO-C-H H-C-OH H-C-OH HO-C-H HO-C-H
I I I I I I I I
H-C-OH H-C-OH H-C-OH H-C-OH HO-C-H HO-C-H HO-C-H HO-C-H
I I I I I I I I
H- C-OH H-C-OH H-C-OH H-C-OH H-C-OH H-C-OH H-C-OH H-C-OH
I I I I I I I I

I o-Glucose I I o-Mannose I I o-Galactose I

CH20H CH20H CH20H CH20H CH20H CH20H CH20H CH20H

o-Allose o-Altrose o-Gulose o-Idose o-Talose

n-Aldoses
(a )

FIGURE 7-3 Aldoses and ketoses. The series of (a) D-a l doses and
Three cro·bons Four carbons
(b) D-ketoses having from th ree to six carbon atoms, shown as projec­
tion form u l as. The carbon atoms in red are ch i ral centers. In a l l these
D isomers, the ch i ral carbon most distant from the carbonyl carbon has
the same configuration as the ch i ra l carbon in D-glyceraldehyde. The
sugars named in boxes are the most common in nature; you w i l l en­

I Dihydroxyacelone I I o-Erythrulose I
counter these aga i n in this and later chapters.

2n stereoisomers. Glyceraldehyde has 2 = 2; the aldo­

In general, a molecule with n dural centers can have
1
hexoses, with four chiral centers, have 2 4 16 stereoiso­=
Five carbons Six carbons
mers. The stereoisomers of monosaccharides of each
CH20H CH20H

I
carbon-chain length can be divided into two groups that CH20H I I
differ in the configuration about the chiral center most C=O C=O
I I
I
C=O
distant from the carbonyl carbon. Those in which the I H-C-OH HO-C-H
configuration at this reference carbon is the same as H-C-OH I
H-C-OH H- C-OH
I
that of D-glyceraldehyde are designated D isomers, and H- C-OH I I
H- C-OH H-C-OH
those with the same configuration as L-glyceraldehyde I

I o-Ribulose I
CH20H I I

I D-Fructose I
CH20H CH20H
are 1 isomers. When the hydroxyl group on the refer­
ence carbon is on the right in a projection formula that o-Psicose

has the carbonyl carbon at the top, the sugar is the D iso­
mer; when on the left, it is the 1 isomer. Of the 1 6 possi­ CH20H CH20H
I I
ble aldohexoses, eight are D forms and eight are 1. Most CH20H C=O C=O
I I I
I
of the hexoses of living organisms are D isomers. C=O H-C-OH HO-C-H
Figure 7-3 shows the structures of the D stereoiso­ I I
I
HO-C-H HO-C-H HO-C-H
mers of all the aldoses and ketoses having three to six I I
H-C-OH H-C-OH H-C-OH
carbon atoms. The carbons of a sugar are numbered be­ I I I

I D-Xylulose I
ginning at the end of the chain nearest the carbonyl CH20H CH20H CH20H

group. Each of the eight D-aldohexoses, which differ in o-Sorbose o-Tagatose

the stereochemistry at C-2 , C-3, or C-4, has its own
name: D-glucose, D-galactose, D-mannose, and so forth n-Ketoses
(Fig. 7-3a) . The four- and five-carbon ketoses are (b)
[23s] Carbohydrates a n d G l yco b i o l o gy

1CHO 1CHO 1CHO

21 21 21
HO-C-H H-C-OH H-C- OH
3I 31 3I
HO-C-H HO -C-H HO-C-H
41 41 41 Aldehyde Alcohol Hemiacetal
H-C-OH H-C-OH HO -C-H
sl sl

<=="'""{�== R- 1 -OR
51
I I I
H-C-OH H-C-OH H-C- OH
6CH20H
D-Mannose
6CH20H
D-Glucose
6CH20H
n-Galactose 1
R-C=O + H O-R
3 _____,.
�
OH
1 1
R-C-OR
3
HO-R4
3 1 1
OR4
C + HzO
(epimer at C-2) (epimer at C-4) 12 12 2
R R HO-R R
FIGURE 7-4 Epimers. o-Gi ucose and two of its epimers are shown as Ketone Alcohol Hemiketal Ketal
projection formul as. Each epimer d i ffers from o-glucose in the config­
FIGURE 7-5 Formation of hemiacetals and hemiketals. An al dehyde
uration at one chiral center (shaded p i n k) .
or ketone can react with an alcohol in a 1 : 1 ratio to yield a hemiacetal
or hemiketal, respectively, creating a new chiral center at the carbonyl
designated by inserting "ul" into the name of a corre­ carbon. Substitution of a second alcohol molecule produces an acetal
sponding aldose; for example, D-ribulose is the ketopen­ or ketal . When the second alcohol is part of another sugar molecule,
tose corresponding to the aldopentose D-ribose. The the bond produced i s a glycosidic bond (p. 243).
ketohexoses are named otherwise: for example, fruc­
tose (from the Latin fructus, "fruit"; fruits are one
carbon asymmetric and producing two stereoisomers,
source of this sugar) and sorbose (from Sorbus , the
designated a and {3 (Fig. 7-6) . The designation a indi­
genus of mountain ash, which has berries rich in the re­
cates that the hydroxyl group at the anomeric center
lated sugar alcohol sorbitol). 1\vo sugars that differ only
is, in a Fischer projection, on the same side as the
in the configuration around one carbon atom are called

{cf
epimers; D-glucose and D-mannose, which differ only in
the stereochemistry at C-2, are epimers, as are D-glu­
H 0
cose and D-galactose (which differ at C-4) (Fig. 7-4) .
l
Some sugars occur naturally in their L form; 2
examples are L-arabinose and the L isomers of some H-C-OH

tI
3I
4I
sugar derivatives that are common components of HO- C-H n-Glucose
glycoconjugates (Section 7. 3). H-C-OH

.
H� -o:H

c
H 0
"- f' 6 CH20H
I
H-C-OH

I 2

46I'�
I 6 CH OH
---
H
HO-C-H

H
H6\ 1
JI
I 6C 'O H
HO-C-H

3?H 2?OH
I

1/ �
CH20H C1
H
L-Arabinose
___

The Common Monosaccharides Have Cyclic Structures

For simplicity, we have thus far represented the struc­

tures of aldoses and ketoses as straight-chain mole­ # '

46 HH 461
cules (Figs 7- 3, 7-4). In fact, in aqueous solution, fi CH20H 6 CH20H

\
sc
/1 jHl
I I
0

H6\� 1 / "oa
JI
aldotetroses and all monosaccharides with five or more 5C 0
H H

ay
/OH

?
carbon atoms in the backbone occur predominantly as
H
1/
IC 1C
HO I
cyclic (ring) structures in which the carbonyl group H 0H "
\ H

aI
has formed a covalent bond with the oxygen of a hy­

2�H
2
droxyl group along the chain. The formation of these
H H OH
ring structures is the result of a general reaction be­
a-n-Glucopyranose ,8-n-Glucopyranose
tween alcohols and aldehydes or ketones to form deriv­
atives called hemiacetals or hemiketals (Fig. 7-5 ) , FIGURE 7-6 Formation of the two cyclic forms of D-glucose. Reac­
which contain an additional asymmetric carbon atom tion between the a ldehyde group at C-1 and the hydroxyl group at C-5
and thus can exist in two stereoisomeric forms. For ex­ forms a hemiacetal l i nkage, producing either of two stereoisomers, the
ample, D-glucose exists in solution as an intramolecular a and f3 anomers, which differ only in the stereochemi stry around the
hemiacetal in which the free hydroxyl group at C-5 has hemiacetal carbon. The interconvers ion of a and f3 anomers is cal led
reacted with the aldehydic C-1 , rendering the latter mutarotation.
 7 . 1 Monosaccharides and Disaccha rides [239]
hydroxyl attached at the farthest chiral center, whereas {3-D-glucose, and very small amounts of the linear and
f3 indicates that these hydroxyl groups are on opposite five-membered ring (glucofuranose) forms.
sides. These six-membered ring compounds are called Ketohexoses also occur in a and f3 anomeric forms.
pyranoses because they resemble the six-membered In these compounds the hydroxyl group at C-5 (or C-6)
ring compound pyran (Fig. 7-7). The systematic names reacts with the keto group at C-2 , forming a furanose (or
for the two ring forms of D-glucose are a-D-glucopyranose pyranose) ring containing a hemiketal linkage (Fig. 7-5) .
and {3-D-glucopyranose. D-Fructose readily forms the furanose ring (Fig. 7-7) ;
Aldoses also exist in cyclic forms having five­ the more common anomer of this sugar in combined
membered rings, which, because they resemble the five­ forms or in derivatives is {3-D-fructofuranose.
membered ring compound furan, are called furanoses. Haworth perspective formulas like those in Fig­
However, the six-membered aldopyranose ring is much ure 7-7 are commonly used to show the stereochemistry
more stable than the aldofuranose ring and predomi­ of ring forms of monosaccharides. However, the six­
nates in aldohexose and aldopentose solutions. Only al­ membered pyranose ring is not planar, as Haworth per­
doses having five or more carbon atoms can form spectives suggest, but tends to assume either of two
pyranose rings. "chair" conformations (Fig. 7-8). Recall from Chapter 1
Isomeric forms of monosaccharides that differ only (p. 18) that two conformations of a molecule are inter­
in their configuration about the hemiacetal or hemiketal convertible without the breakage of covalent bonds,
carbon atom are called anomers. The hemiacetal (or whereas two configurations can be interconverted only
carbonyl) carbon atom is called the anomeric carbon. by breaking a covalent bond. To interconvert a and f3
The a and f3 anomers of D-glucose interconvert in configurations, the bond involving the ring oxygen atom
aqueous solution by a process called mutarotation would have to be broken, but interconversion of the two
(Fig. 7-6). Thus, a solution of a-D-glucose and a solution chair forms does not require bond breakage. The specific
of {3-D-glucose eventually form identical equilibrium three-dimensional structmes of the monosaccharide units
mixtures having identical optical properties. This mix­ are important in determining the biological properties and
ture consists of about one-third a-D-glucose, two-thirds functions of some polysaccharides, as we shall see.

Axis
ax ax
eq eq

4 eq eq

ax

OH Two possible chair forms

(a)
a-D-Glucopyranose a-D-Fructofuranose
Axis

H OH OH H
,8-D-Fructofuranose
a-D-Glucopyranose
,8-D-Glucopyranose
(b)

FIGURE 7-8 Conformational formulas of pyranoses. (a) Two chair

0
forms of the pyranose ring . Bonds to substituents and hydrogen atoms
HC/ �CH
\c I
on the ring carbons may be either axial (ax), projecting parallel to the
vertical axis through the ring, or equatorial (eq), projecting roughly
- c
H H perpendicular to this axis. Two conformers such are these are not readily
i nterconvertible without breaking the ring. However, when the mole­
Pyran Furan
cule is "stretched" (by atomic force microscopy; see Box 1 1 - 1 ), an
FIGURE 7-7 Pyranoses and furanoses. The pyranose forms of i nput of about 46 kj of energy per mole of sugar can force the inter­
o-gl ucose and the furanose forms of o-fructose are shown here as Ha­ conversion of chair forms. Genera l ly, substituents i n the equatorial
worth perspective formulas. The edges of the r i ng nearest the reader positions are less sterica l l y h i ndered by neighboring substituents, and
are represented by bold l i nes. Hydroxyl groups below the plane of the conformers with bulky substituents i n equatorial positions are favored.
ring i n these Haworth perspectives wou ld appear at the right side of a Another conformation, the "boat" (not shown), is seen only in deriva­
Fischer projection (compare with Fig. 7-6). Pyran and furan are shown tives with very bulky substituents. (b) The preferred cha i r conformation
for comparison. of a-D-gl ucopyranose.
[240] Carbohydrates a n d G l ycob iology

Organisms Contain a Variety of H exose Derivatives

or 1-mannose produces 1-fucose or 1-rhamnose , re­
In addition to simple hexoses such as glucose, galactose, spectively. 1-Fucose is found in the complex oligosac­
and mannose, there are a number of sugar derivatives in charide components of glycoproteins and glycolipids;
which a hydroxyl group in the parent compound is re­ 1-rhamnose is found in plant polysaccharides.
placed with another substituent, or a carbon atom is ox­ Oxidation of the carbonyl (aldehyde) carbon of glu­
idized to a carboxyl group (Fig. 7-9). In glucosamine, cose to the carboxyl level produces gluconic acid; other
galactosamine , and mannosamine, the hydroxyl at C-2 aldoses yield other aldonic acids. Oxidation of the car­
of the parent compound is replaced with an amino bon at the other end of the carbon chain-C-6 of glucose,
group. The amino group is nearly always condensed galactose, or mannose-forms the corresponding uronic
with acetic acid, as in N-acetylglucosamine. This acid: glucuronic, galacturonic, or mannuronic acid. Both
glucosamine derivative is part of many structural poly­ aldonic and uronic acids form stable intramolecular es­
mers, including those of the bacterial cell wall. Bacter­ ters called lactones (Fig. 7-9 , lower left) . In addition
ial cell walls also contain a derivative of glucosamine, to these acidic hexose derivatives , one nine-carbon
N-acetylmuramic acid, in which lactic acid (a three­ acidic sugar deserves mention: N-acetylneuraminic acid
carbon carboxylic acid) is ether-linked to the oxygen (a sialic acid, but often referred to simply as "sialic acid") ,
at C-3 of N-acetylglucosamine. The substitution of a a derivative of N-acetylmannosamine, is a component
hydrogen for the hydroxyl group at C-6 of L-galactose of many glycoproteins and glycolipids in animals. The

Glucose family

Amino sugar

H H

�0
H OH NH H NH2
j3-o-Galactosamine ,8-o-Mannosamine
I
CH
/3-D-Glucose p -o-Gl ucosamine -Acetyl-,9-o-glu�;o amin

�
Deoxy sugars

H H
O
H HO 3 OH

H H
H
f
H NH OH H OH H

/3-D-Glucose 6-phosphate Muramic acid N-Acetylmuramic acid ,8-L-Fucose a-L-Rhamnose

Acidi sugars

R=

I
I
0 H - C - OH

I
H - C - OH

H H OH H OH OH R CH20H

/3-D-Glucuronate o-Gl uconate o-Glucono-8-lactone N-Acetylneuraminic acid

(a sialic acid)

FIGURE 7-9 Some hexose derivatives important in biology. I n a m i no acidic sugars contain a carboxyl ate group, which confers a negative
sugars, an -N H 2 group replaces one of the -OH groups in the parent charge at neutral p H . o-Giucono-IJ-Iactone results from formation of
hexose. Substitution of -H for -OH produces a deoxy sugar; note an ester l i n kage between the C-1 carboxylate group and the C-5 (also
that the deoxy sugars shown here occur in nature as the L isomers. The known as the /J carbon) hydroxyl group of o-gluconate.
 7 . 1 Monosaccharides a n d Disaccha rides [241]

carboxylic acid groups of the acidic sugar derivatives

are ionized at pH 7, and the compounds are therefore
correctly named as the carboxylates-glucuronate,
galacturonate, and so forth.
In the synthesis and metabolism of carbohydrates,
the intermediates are very often not the sugars them­ Complex mixture of
2-,3-,4-, and
selves but their phosphorylated derivatives. Condensa­ 6-carbon acids
tion of phosphoric acid with one of the hydroxyl groups
of a sugar forms a phosphate ester, as in glucose n-Glucose
6-phosphate (Fig. 7-9). Sugar phosphates are relatively (linear form)
stable at neutral pH and bear a negative charge. One ef­
FIGURE 7-10 Sugars as reducing agents. Oxidation of the anomeric
fect of sugar phosphorylation within cells is to trap the carbon (and probably the neighboring carbon) of glucose and other
sugar inside the cell; most cells do not have plasma sugars under alkaline conditions is the basis for Fehl ing's reaction. The
membrane transporters for phosphorylated sugars. cuprous ion (Cu+) produced forms a red cuprous oxide precipitate. In
Phosphorylation also activates sugars for subsequent the hemiacetal (ring) form, C-1 of glucose cannot be oxidized by
chemical transformation. Several important phosphory­ complexed Cu2+ . However, the open-chain form is in equ i librium
lated derivatives of sugars are components of nu­ with the ring form, and eventually the oxidation reaction goes to com­
cleotides (discussed in the next chapter) . pletion. The reaction with Cu2+ is complex, yielding a m i xture of prod­
ucts and reducing 3 mol of Cu2+ per mole of glucose.
Monosaccharides Are Reducing Agents

Monosaccharides can be oxidized by relatively acids. This is the basis of Fehling's reaction, a qualitative
2
mild oxidizing agents such as cupric (Cu +) ion test for the presence of reducing sugar. By measuring
(Fig. 7-10). The carbonyl carbon is oxidized to a car­ the amount of oxidizing agent reduced by a solution of a
boxyl group. Glucose and other sugars capable of sugar, it is also possible to estimate the concentration of
reducing cupric ion are called reducing sugars. They that sugar. For many years this test was used to detect
form enediols, which are converted to aldonic acids and and measure elevated glucose levels in blood and urine
then to a complex mixture of 2-, 3-, 4-, and 6-carbon in the diagnosis of diabetes mellitus (Box 7-1). •

B l o o d G l ucose M e a s u re m e n ts i n t h e D i a g n os i s a n d
B OX 7 - 1
Tre a t m e n t o f D i a betes
------ -- ---
-- � �--------�------�L------

Glucose is the principal fuel for the brain. When the The concentrations of glucose in blood and urine
amount of glucose reaching the brain is too low, the can be determined by a simple assay for reducing sugar,
consequences can be dire: lethargy, coma, permanent such as Fehling's reaction, which for many years was
brain damage, and death (see Fig. 23-25) . Animals used as a diagnostic test for diabetes (Fig. 7-1 0) . Mod­
have evolved complex hormonal mechanisms to ensure ern measurements require just a drop of blood, added
that the concentration of glucose in the blood remains to a test strip containing the enzyme glucose oxidase
high enough (about 5 mM) to satisfy the brain's needs, (Fig. 1); a simple photometer measures the color pro­
but not too high, because elevated blood glucose can duced when the H202 from glucose oxidation reacts with
also have serious physiological consequences. a dye, and reads out the blood glucose concentration.
Individuals with insulin-dependent diabetes melli­ Because blood glucose levels change with the timing
tus do not produce sufficient insulin, the hormone that of meals and exercise, single-time measurements do not
normally serves to reduce blood glucose concentration, necessarily reflect the average blood glucose over hours
and if the diabetes is untreated their blood glucose lev­ and days, so dangerous increases may go undetected.
els may rise to severalfold higher than normal. These The average glucose concentration can be assessed by
high glucose levels are believed to be at least one cause looking at its effect on hemoglobin, the oxygen-carrying
of the serious long-term consequences of untreated dia­ protein in erythrocytes (p. 1 58) . Transporters in the ery­
betes-kidney failure, cardiovascular disease, blind­ throcyte membrane equilibrate intracellular and plasma
ness, and impaired wound healing-so one goal of j.!IUL / 1�1 HXId.l
n-Glucose + 02 � n-Glucono-8-lactone + H202
therapy is to provide just enough insulin (by injection)
to keep blood glucose levels near normal. To maintain FIGURE 1 The glucose oxidase reaction, used in the measurement of
the correct balance of exercise, diet, and insulin for the blood glucose. A second enzyme, a peroxidase, catalyzes the reaction
individual, blood glucose concentration needs to be of the H202 with a colorless compound to produce a colored product,
measured several times a day, and the amount of insulin which is measured spectrophotometrically.
injected adjusted appropriately. (continued on next page)
[242] Carbohydrates a n d Glycobiology

B l oo d G l u cose M e a s u r e m e nts i n t h e D i a g n os i s a n d
Treat m e n t o f D i a betes (continued from previous page)
BOX 7-1
� ·�����----� �

glucose concentrations, so hemoglobin is constantly ex­

posed to glucose at whatever concentration is present in OH
H
H
the blood. A nonenzymatic reaction occurs between glu­ I
C = O + H2N - R
cose and primary amino groups in hemoglobin (either H
Hemoglobin
the amino-terminal Val or the e-amino groups of Lys
residues; see Fig. 2). The rate of this process is propor­ H OR

<D l
tional to the concentration of glucose, so the reaction Glucose
can be used as the basis for estimating the average blood
glucose level over weeks. The amount of glycated hemo­
globin (GHB) present at any time reflects the average
HO H2
blood glucose concentration over the circulating "life­

I
time" of the erythrocyte (about 1 20 days), although the H
H
concentration in the last two weeks is the most impor­ C=N-R
tant in setting the level of GHB. HO
The extent of hemoglobin glycation (so named
to distinguish it from glycosylation, the enzymatic H OH
Schiff base
transfer of glucose to a protein) is measured clinically
by extracting hemoglobin from a small sample of blood
and separating GHB from unmodified hemoglobin elec­
trophoretically, taking advantage of the charge differ­
HO 2
ence resulting from modification of the amino OR
group(s). Normal GHB values are about 5% of total he­ H
\ H

#
moglobin (corresponding to blood glucose of 1 2 0 mg/ C-N-R
100 mL). In people with untreated diabetes, how­
ever, this value may be as high as 13% , indicating an
H OH
average blood glucose level of about 300 mg/100 mL­
dangerously high. One criterion for success in an indi­
vidual program of insulin therapy (the timing,
frequency, and amount of insulin injected) is maintain­
ing GHB values at about 7% .
In the hemoglobin glycation reaction, the first step
(formation of a Schiff base) is followed by a series of re­
arrangements, oxidations, and dehydrations of the car­
bohydrate moiety to produce a heterogeneous mixture
of AGEs, advanced glycation end products. These prod­
ucts can leave the erythrocyte and form covalent cross­ Keto amine
links between proteins, interfering with normal protein
function (Fig. 2). The accumulation of relatively high
concentrations of AGEs in people with diabetes may, by
H
cross-linking critical proteins, cause the damage to the CH2 - N - R
kidneys, retinas, and cardiovascular system that charac­
terize the disease. This pathogenic process is a potential OH
target for drug action.
HO H
t Glycated hemoglobin
FIGURE 2 The nonenzymatic reaction of glucose with a primary amino @t (GHB)

group in hemoglobin begins with CD formation of a Schiff base, which t

Q) undergoes the Amadori rearrangement to generate a stable product;
CD this ketoam i ne can further cyc l i ze to yield GHB. @ Subsequent
AGEs
/@ t '">I

e-N-carboxymethyl lysine and methylglyoxal, compounds that G) can

reactions generate advanced glycation end products (AGEs), such as
Protein cross-linking

damage other proteins by cross- l i nking them, causing pathological

t? t? t?
changes. Damage to kidneys, retinas, cardiovascular system
 7 . 1 Monosaccharides a n d D i saccha rides [243]

Disaccharides Contai n a Glycosidic Bond The disaccharide maltose (Fig. 7-1 1 ) contains two
o-glucose residues joined by a glycosidic linkage be­
Disaccharides (such as maltose , lactose, and sucrose)
tween C- 1 (the anomeric carbon) of one glucose
consist of two monosaccharides joined covalently by an
residue and C-4 of the other. Because the disaccharide
0-glycosidic bond, which is formed when a hydroxyl
retains a free anomeric carbon (C-1 of the glucose
group of one sugar reacts with the anomeric carbon of
residue on the right in Fig. 7-1 1) , maltose is a reducing
the other (Fig. 7-1 1 ) . This reaction represents the for­ sugar. The configuration of the anomeric carbon atom
mation of an acetal from a hemiacetal (such as glucopy­
in the glycosidic linkage is a. The glucose residue with
ranose) and an alcohol (a hydroxyl group of the second the free anomeric carbon is capable of existing in a- and
sugar molecule) (Fig. 7-5) , and the resulting compound
{3-pyranose forms.
is called a glycoside. Glycosidic bonds are readily
hydrolyzed by acid but resist cleavage by base. Thus K EY C O N V E N T I O N : To name reducing disaccharides such
disaccharides can be hydrolyzed to yield their free
as maltose unambiguously, and especially to name more
monosaccharide components by boiling with dilute acid. complex oligosaccharides, several rules are followed. By
N-glycosyl bonds join the anomeric carbon of a sugar to convention, the name describes the compound written
a nitrogen atom in glycoproteins (see Fig. 7-29) and nu­ with its nonreducing end to the left, and we can "build
cleotides (see Fig. 8-1) . up" the name in the following order. (1) Give the config­
The oxidation of a sugar by cupric ion (the reaction uration (a or /3) at the anomeric carbon joining the first
that defines a reducing sugar) occurs only with the monosaccharide unit (on the left) to the second. (2)
linear form, which exists in equilibrium with the cyclic Name the nonreducing residue; to distinguish five- and
form(s) . When the anomeric carbon is involved in a gly­ six-membered ring structures, insert "furano" or
cosidic bond, that sugar residue cannot take the linear "pyrano" into the name. (3) Indicate in parentheses the
form and therefore becomes a nonreducing sugar. In two carbon atoms joined by the glycosidic bond, with an
describing disaccharides or polysaccharides, the end of a arrow connecting the two numbers; for example, (1�4)
chain with a free anomeric carbon (one not involved in a shows that C-1 of the first-named sugar residue is joined
glycosidic bond) is commonly called the reducing end. to C-4 of the second. (4) Name the second residue. If
there is a third residue, describe the second glycosidic
bond by the same conventions. (To shorten the descrip­
h l' m l acPtal tion of complex polysaccharides, three-letter abbrevia­
tions or colored symbols for the monosaccharides
+ are often used, as given in Table 7-1 .) Following this
convention for naming oligosaccharides, maltose is a-o­

[
glucopyranosyl-(1 �4)-o-glucopyranose. Because most
H OH
sugars encountered in this book are the o enantiomers
a-D-Glucose {3-D-Glucose
and the pyranose form of hexoses predominates, we

�>
hydrolysis concl n�allon generally use a shortened version of the formal name of
n "u

TA B L E 7- 1
hl•mi:u:t•t.tl
OR
Abequose Abe Glucuronic acid � GlcA
0 GaiN
H
0 Arabinos e Ara Galactosamine

Fructose Fru Gluc os amine � GleN

Maltose Fucose A Fuc N-Acetylgalactosamine 0 GalNAc
• GlcNAc
a-o-glucopyranosyl-(1�4)-D-glucopyranose
Galactose 0 Gal N-Acetylglucosamine
FIGURE 7-1 1 Formation of maltose. A disaccharide is formed from Glucose e Glc Iduronic acid � IdoA
two monosaccharides (here, two molecules of o-glucose) when an
Mannose e Man Muramic acid Mur
-OH (alcohol) of one gl ucose molecule (right) condenses with the i n ­
Rhamnose Rha N-Acetylmuramic acid Mur2Ac
tramolecular hem i acetal o f t h e other glucose molecule (left), with

+ Neu5Ac
e l i m i nation of H20 and formation of a glycosidic bond. The reversal of Ribose Rib N-Acety!neuraminic
this reaction is hydrolysis-attack by H20 on the glycosidic bond. The Xylose * Xyl acid (a sialic acid)
maltose molecule, shown here as an i l l ustration, reta i ns a reducing
hemiacetal at the C-1 not involved i n the glycosidic bond. Because Note: In a commonly used convention, hexoses are represented as circles, N-acetylhex­
mutarotation interconverts the a and {3 forms of the hem i acetal, the osamines as squares, and hexosamines as squares divided diagonally. All sugars With
the "gluco' configuration are blue, those with the "galacto' configuration are yellow, and
bonds at this position are sometimes depi cted with wavy l i nes, as "manno" sugars are green. Other substituents can be added as needed: sulfate (S).
shown here, to i n d i cate that the structure may be either a or {3 . phosphate (P), 0-acetyl (OAc), or 0-methyl (Orne).
[_244j Ca rbohyd rates a n d G lycobiology

such compounds, glVlng the configuration of the (Fig. 7-12)-a disaccharide of o-glucose that, like su­
anomeric carbon and naming the carbons joined by crose, is a nonreducing sugar-is a major constituent of
the glycosidic bond. In this abbreviated nomenclature, the circulating fluid (hemolymph) of insects, serving as
maltose is Glc(al�4)Glc. • an energy-storage compound. Fungi also contain tre­
halose and are used as a commercial source of this sugar.
The disaccharide lactose (Fig. 7-12), which yields
o-galactose and o-glucose on hydrolysis, occurs naturally S U M M A RY 7 . 1 Monos a c c h ari des and
in milk. The anomeric carbon of the glucose residue is
D is a c c h a ri des
available for oxidation, and thus lactose is a reducing di­
saccharide. Its abbreviated name is Gal(f3 1�4)Glc. • Sugars (also called saccharides) are compounds
Sucrose (table sugar) is a disaccharide of glucose and containing an aldehyde or ketone group and two or
fructose. It is formed by plants but not by animals. In more hydroxyl groups.
contrast to maltose and lactose, sucrose contains no free • Monosaccharides generally contain several chiral
anomeric carbon atom; the anomeric carbons of both carbons and therefore exist in a variety of
monosaccharide units are involved in the glycosidic bond stereochemical forms, which may be represented
(Fig. 7-12) . Sucrose is therefore a nonreducing sugar. on paper as Fischer projections. Epimers are sugars
In the abbreviated nomenclature, a double-headed that differ in configuration at only one carbon atom.
arrow connects the symbols specifying the anomeric
carbons and their configurations. For example, the ab­ • Monosaccharides commonly form internal
breviated name of sucrose is either Glc(a l�2f3)Fru or hemiacetals or hemi.ketals, in which the aldehyde
Fru(f32�la) Glc. Sucrose is a major intermediate prod­ or ketone group joins with a hydroxyl group of the
uct of photosynthesis; in many plants it is the principal same molecule, creating a cyclic structure; this can
form in which sugar is transported from the leaves to be represented as a Haworth perspective formula.
other parts of the plant body. Trehalose, Glc(al�la)Glc The carbon atom originally found in the aldehyde or
ketone group (the anomeric carbon) can assume
either of two configurations, a and /3, which are
interconvertible by mutarotation. In the linear form,
which is in equilibrium with the cyclic forms, the
anomeric carbon is easily oxidized.
• A hydroxyl group of one monosaccharide can add to
the anomeric carbon of a second monosaccharide to
form an acetal. In this disaccharide, the glycosidic
Lactose (/3 form) bond protects the anomeric carbon from oxidation.
/3-n-galactopyranosyl-(1�4)-/3-n-glucopyranose
Gai(f31�4)Glc
• Oligosaccharides are short polymers of several
monosaccharides joined by glycosidic bonds. At
one end of the chain, the reducing end, is a
monosaccharide unit with its anomeric carbon
not involved in a glycosidic bond.
• The common nomenclature for di- or oligosaccharides
specifies the order of monosaccharide units, the
configuration at each anomeric carbon, and the
Sucrose carbon atoms involved in the glycosidic linkage(s).
/3-D-fructofuranosyl a-D-glucopyranoside
Fru(2f3 - al)Glc = Glc(al -2f3)Fru
7.2 Polysaccharides
H
Most carbohydrates found in nature occur as polysac­
charides, polymers of medium to high molecular weight.
Polysaccharides, also called glycans, differ from each
other in the identity of their recurring monosaccharide
units, in the length of their chains, in the types of bonds
Trehalose linking the units, and in the degree of branching.
a-o-glucopyranosyl a-o-glucopyranoside Homopolysaccharides contain only a single monomeric
Glc(al<--> la)Glc
species; heteropolysaccharides contain two or more
FIGURE 7-12 Some common disaccharides. Like ma ltose in Figure different kinds (Fig. 7-13). Some homopolysaccharides
7-1 1 , these are shown as Haworth perspectives. The common name, serve as storage forms of monosaccharides that are used
fu l l systematic name, and abbreviation are given for each disaccharide. as fuels; starch and glycogen are homopolysaccharides of
Formal nomenclature for sucrose names glucose as the parent glyco­ this type. Other homopolysaccharides (cellulose and
side, although it is typica l l y depicted as shown, with gl ucose on the left. chitin, for example) serve as structural elements in plant
 7 . 2 Polysa ccharides [245]
Homopolysaccharides Heteropolysaccharides space is occupied by several types of heteropolysaccha­
Unbranched Branched Two Multiple rides, which form a matrix that holds individual cells to­
monomer monomer gether and provides protection, shape, and support to
types, types, cells, tissues, and organs.
unbranched branched
Unlike proteins, polysaccharides generally do not
have defining molecular weights. This difference is a
consequence of the mechanisms of assembly of the two
types of polymer. As we shall see in Chapter 27, proteins
are synthesized on a template (messenger RNA) of de­
fined sequence and length, by enzymes that follow the
template exactly. For polysaccharide synthesis there is
no template; rather, the program for polysaccharide
synthesis is intrinsic to the enzymes that catalyze the
polymerization of the monomeric units, and there is no
specific stopping point in the synthetic process.

Some H o mopolysaccharides Are Stored Forms of Fuel

The most important storage polysaccharides are starch

FIGURE 7-1 3 Homo- and heteropolysaccharides. Polysaccharides in plant cells and glycogen in animal cells. Both polysac­
may be composed of one, two, or several different monosaccharides, charides occur intracellularly as large clusters or gran­
in straight or branched chains of varying l ength . ules. Starch and glycogen molecules are heavily
hydrated, because they have many exposed hydroxyl
cell walls and animal exoskeletons. Heteropolysaccha­ groups available to hydrogen-bond with water. Most
rides provide extracellular support for organisms of all plant cells have the ability to form starch (see Fig. 20-2) ,
kingdoms. For example, the rigid layer of the bacterial and starch storage is especially abundant in tubers
cell envelope (the peptidoglycan) is composed in part of (underground stems) , such as potatoes, and in seeds.
a heteropolysaccharide built from two alternating mono­ Starch contains two types of glucose polymer, amy­
saccharide units. In animal tissues, the extracellular lose and amylopectin (Fig. 7-14). The former consists

L
Noureducing Reducing
end end
0 0 0
H OR

(a) Amylose

0 (a1�6)
branch Amylose
Branch H OH point

I
0

0
6 CH2

O J
Nonreducing
ends
- - }""'"'"'•
ends

Main R OR
chain

( b) (c)
FIGURE 7-14 Glycogen and starch. (a) A short segment of amylose, a amylose and amylopectin l i ke that believed to occur i n starch gran u les.
l i near polymer of o-glucose residues in (al �4) l i n kage. A single chain Strands of amylopectin (red) form double-helical structu res with each
can contain several thousand gl ucose residues. Amyl opect i n has other or with amylose strands (blue). G l ucose residues at the nonreduc­
stretches of s i m i larly l i n ked residues between branch points. G lycogen ing ends of the outer branches are removed enzymatically during the
has the same basic structure, but has more branchi ng than amylopectin. mobilization of starch for energy production. Glycogen has a similar
(b) An (al �6) branch point of glycogen or amylopectin. (c) A cluster of structure but is more high l y branched and more compact.
[246] Carbohydrates a n d G l ycobiology

of long, unbranched chains of o-glucose residues con­ Some Homo polysaccharides Serve Structural Roles
nected by (al�4) linkages (as in maltose) . Such chains
vary in molecular weight from a few thousand to more Cellulose, a fibrous, tough, water-insoluble substance, is
than a million. Amylopectin also has a high molecular found in the cell walls of plants, particularly in stalks,
weight (up to 200 million) but unlike amylose is highly stems, trunks, and all the woody portions of the plant
branched. The glycosidic linkages joining successive body. Cellulose constitutes much of the mass of wood,
glucose residues in amylopectin chains are (al�4) ; the and cotton is almost pure cellulose. Like amylose, the
branch points (occurring every 24 to 30 residues) are cellulose molecule is a linear, unbranched homopolysac­
(a l�6) linkages. charide, consisting of 10,000 to 1 5,000 o-glucose units.
Glycogen is the main storage polysaccharide of But there is a very important difference: in cellulose the
animal cells. Like amylopectin, glycogen is a polymer of glucose residues have the f3 configuration (Fig. 7-1 5 ) ,
(a l�4)-linked subunits of glucose, with (a1�6)-linked whereas in amylose the glucose is in the a configuration.
branches, but glycogen is more extensively branched The glucose residues in cellulose are linked by ({31�4)
(on average, every 8 to 12 residues) and more compact glycosidic bonds, in contrast to the (a1�4) bonds of
than starch. Glycogen is especially abundant in the liver, amylose . This difference gives cellulose and amylose
where it may constitute as much as 7% of the wet very different structures and physical properties.
weight; it is also present in skeletal muscle. In hepato­ Glycogen and starch ingested in the diet are hy­
cytes glycogen is found in large granules, which are drolyzed by a-amylases and glycosidases, enzymes in
themselves clusters of smaller granules composed of saliva and the intestine that break (a1�4) glycosidic
single, highly branched glycogen molecules with an bonds between glucose units. Most animals cannot use
average molecular weight of several million. Such glyco­ cellulose as a fuel source, because they lack an enzyme
gen granules also contain, in tightly bound form, the to hydrolyze the ({31�4) linkages. Termites readily di­
enzymes responsible for the synthesis and degradation gest cellulose (and therefore wood) , but only because
of glycogen. their intestinal tract harbors a symbiotic microorganism,
Because each branch in glycogen ends with a nonre­
ducing sugar unit, a glycogen molecule with n branches
has n + 1 nonreducing ends, but only one reducing end. OH I l l OH

When glycogen is used as an energy source, glucose units

\
are removed one at a time from the nonreducing ends. 0
Degradative enzymes that act only at nonreducing ends
can work simultaneously on the many branches, speeding
the conversion of the polymer to monosaccharides. ({:ll-->4)-linked o-glucose units

Why not store glucose in its monomeric form? It has ( a)

been calculated that hepatocytes store glycogen equiva­
lent to a glucose concentration of 0.4 M. The actual
concentration of glycogen, which is insoluble and con­
tributes little to the osmolarity of the cytosol, is about
0.01 J.LM . If the cytosol contained 0.4 M glucose, the
osmolarity would be threateningly elevated, leading to
osmotic entry of water that might rupture the cell (see
Fig. 2-12) . Furthermore, with an intracellular glucose
concentration of 0.4 M and an external concentration of
about 5 mM (the concentration in the blood of a mam­
mal) , the free-energy change for glucose uptake into
cells against this very high concentration gradient would
be prohibitively large.
Dextrans are bacterial and yeast polysaccharides
made up of (al�6) -linked poly-o-glucose ; all have
(a 1�3) branches, and some also have (a 1�2) or
(a1�4) branches. Dental plaque, formed by bacteria FIGURE 7-15 Cellulose. (a) Two units of a cel lulose chain; the o-glu­
growing on the surface of teeth, is rich in dextrans. Syn­ cose residues are i n ({31 ---+4) linkage. The rigid chair structures can ro­
thetic dextrans are used in several commercial products tate relative to one another. (b) Scale drawing of segments of two
(for example, Sephadex) that serve in the fractionation parallel cel l u lose chains, showing the conformation of the o-glucose
of proteins by size-exclusion chromatography (see residues and the hydrogen-bond cross- l i n ks. In the hexose unit at the
Fig. 3-1 7b) . The dextrans in these products are chemi­ lower left, all hydrogen atoms are shown; in the other three hexose
cally cross-linked to form insoluble materials of various un its, the hydrogens attached to carbon have been omitted for clarity,
porosities, admitting macromolecules of various sizes. as they do not participate i n hydrogen bonding.
 7.2 Polysaccharides [247]

FIGURE 7-16 Cellulose breakdown by wood fungi. A wood fungus

growing on an oak log. All wood fungi have the enzyme cel l u l ase,
which breaks the ({31 �4) glycosidic bonds in cel l u l ose, so that wood
is a source of metabol izable sugar (gl ucose) for the fungus. The only
vertebrates able to use cellulose as food are cattle and other ruminants
(sheep, goats, camels, gi raffes). The extra stomach compartment
(rumen) of a ruminant teems with bacteria and protists that secrete
cel lulase.

H:J
C=O
I
NH
2
0 0

0
I!
NH H NH
I I
C=O C=O
I I
(a) CH3 CH3
FIGURE 7-1 7 Chitin. (a) A short segment of chitin, a homopolymer of
N-acetyl-o-glucosamine units in (/31 �4) l i nkage. (b) A spotted june
beetle (Pelidnota punctata), showing its surface armor (exoskeleton)
of chitin .

Steric Factors and Hydrogen Bonding Influence

Homopolysaccharide Folding
The folding of polysaccharides in three dimensions fol­
lows the same principles as those governing polypeptide
structure: subunits with a more-or-less rigid structure
(b) dictated by covalent bonds form three-dimensional
macromolecular structures that are stabilized by weak
interactions within or between molecules: hydrogen
Trichonympha, that secretes cellulase, which hy­ bonds and hydrophobic and van der Waals interactions,
drolyzes the ({31�4) linkages. Wood-rot fungi and bac­ and, for polymers with charged subunits, electrostatic
teria also produce cellulase (Fig. 7-16) . interactions. Because polysaccharides have so many
Chitin is a linear homopolysaccharide composed hydroxyl groups, hydrogen bonding has an especially
of N-acetylglucosamine residues in (131�4) linkage important influence on their structure. Glycogen, starch,
(Fig. 7-17) . The only chemical difference from cellulose and cellulose are composed of pyranoside subunits
is the replacement of the hydroxyl group at C-2 with an (having six-membered rings) , as are the oligosaccha­
acetylated amino group. Chitin forms extended fibers rides of glycoproteins and glycolipids to be discussed
similar to those of cellulose, and like cellulose cannot later. Such molecules can be represented as a series of
be digested by vertebrates. Chitin is the principal com­ rigid pyranose rings connected by an oxygen atom

is , in principle, free rotation about both c-o bonds

ponent of the hard exoskeletons of nearly a million bridging two carbon atoms (the glycosidic bond) . There
species of arthropods-insects, lobsters, and crabs, for
example-and is probably the second most abundant linking the residues (Fig. 7-15a) , but as in polypeptides
polysaccharide, next to cellulose, in nature; an esti­ (see Figs 4-2 , 4-8) , rotation about each bond is lim­
mated 1 billion tons of chitin are produced each year in ited by steric hindrance by substituents. The three­
the biosphere! dimensional structures of these molecules can be
[248] Carbo hyd rates a n d Glycobiology

,�
CH20H �
0 CH20H
described in terms of the dihedral angles, cp and P, about O I I I H OH

cP ·�
Q 4 I

cp and 1Jf made by the peptide bond (see Fig. 4-2) .

the glycosidic bond (Fig. 7-18 ), analogous to angles
4

HO HO O
The bulkiness of the pyranose ring and its sub­
stituents, and electronic effects at the anomeric carbon, C ellulos e
place constraints on the angles cp and P; thus certain (f31--+ 4)Glc repeats

be shown on a map of energy as a function of cp and 1Jf

conformations are much more stable than others, as can

(Fig. 7-19).
The most stable three-dimensional structure for the
(al�4)-linked chains of starch and glycogen is a tightly
coiled helix (Fig. 7-20), stabilized by interchain hydro­
gen bonds. In amylose (with no branches) this structure
is regular enough to allow crystallization and thus deter­ Amylose
(al--+4)Glc repeats
mination of the structure by x-ray diffraction. The aver­
age plane of each residue along the amylose chain forms
a 60° angle with the average plane of the preceding
residue, so the helical structure has six residues per
turn. For amylose, the core of the helix is of precisely

ions (13- and 15-), giving an intensely blue complex. This

the right dimensions to accommodate iodine as complex

interaction is a common qualitative test for amylose.

For cellulose, the most stable conformation is that in
Dextran
which each chair is turned 180° relative to its neighbors,
(al--+6)Glc repeats (with (al--+3) branches, not shown)
yielding a straight, extended chain. All -OH groups are
available for hydrogen bonding with neighboring chains. FIGURE 7-1 8 Conformation at the glycosidic bonds of cellulose, amy­

With several chains lying side by side, a stabilizing network lose, and dextran. The polymers are depicted as rigid pyranose rings
joi ned by glycosidic bonds, with free rotation about these bonds. Note
of interchain and intrachain hydrogen bonds produces
that in dextran there is also free rotation about the bond between C-5
straight, stable suprarnolecular fibers of great tensile
and C-6 (tors ion angle UJ (omega)).
strength (Fig. 7-15b) . This property of cellulose has made
it a useful substance to civilizations for millennia. Many
manufactured products, i ncluding papyrus, paper, card­ these materials is low because extensive interchain hydro­
board, rayon, insulating tiles, and a variety of other useful gen bonding between cellulose molecules satisfies their
materials, are derived from cellulose. The water content of capacity for hydrogen-bond formation.

(a) (b) • f1>,1Jt = - 1 70°, - 170°

FIGURE 7-19 A map of favored conformations for oligosaccharides and energy state, the result is a map of preferred conformations. This is anal­
polysaccharides. The torsion angles 1ft and cfJ (see Fig. 7-1 8), which de­ ogous to the Ramachandran plot for peptides (see Figs 4-3, 4-8).
fine the spatial relationship between adjacent ri ngs, can in principle (b) Two energetic extremes for the disaccharide Gai(J31 --+3)Gal; these
have any value from 0° to 360°. I n fact, some of the torsion angles would values fall on the energy diagram (a) as shown by the red and blue dots .
give conformations that are sterically h i ndered, whereas others give con­ The red dot indicates the least favored conformation, the blue dot the
formations that maximize hydrogen bonding. (a) When the relative en­ most favored conformation. The known conformations of the three poly­
ergy (l) is plotted for each value of ¢ and 1/1, with isoenergy ("same saccharides shown in Figure 7-1 8 have been determined by x-ray crys­
energy") contours drawn at i ntervals of 1 kcal/mol above the m i n i mum tal lography, and a l l fal l with i n the lowest-energy regions of the map.
 7 . 2 Polysaccha r i d es [249]

Agarose
3)n-Gal(f31�4)3,6-anhydro-L-Gal2S(a l repeating units

FIGURE 7-21 Agarose. The repeating u n i t consists of o-galactose

({3 1 ---74)-li nked to 3,6-anhydro-L-galactose (in which an ether bridge
connects C-3 and C-6). These units are joi ned by (a1 ---? 3 ) glycosidic
l i nks to form a polymer 600 to 700 residues long. A small fraction of the
3, 6-anhydrogalactose residues have a su lfate ester at C-2 (as shown here).
(a l-->4)-linked
o-glucose units

(a) (b) useful in the biochemistry laboratory. When a suspen­

sion of agarose in water is heated and cooled, the
FIGURE 7-20 Starch (amylose). (a) In the most stable conformation, with agarose forms a double helix: two molecules in parallel
adjacent rigid chai rs, the polysaccharide chain is curved, rather than l i n­ orientation twist together with a helix repeat of three
ear as in cel l u lose (see Fig. 7-1 5). (b) A model of a segment of amylose; residues; water molecules are trapped in the central
for clarity, the hydroxyl groups have been omitted from a l l but one of the
cavity. These structures in turn associate with each
gl ucose residues. Compare the two residues shaded in pink with the
other to form a gel-a three-dimensional matrix that
chemical structures in (a). The conformation of (a1 -->4) linkages in amy­
traps large amounts of water. Agarose gels are used as
lose, amylopectin, and glycogen causes these polymers to assume tightly
inert supports for the electrophoretic separation of
coiled helical structures. These compact structures produce the dense
nucleic acids, an essential part of the DNA sequencing
granules of stored starch or glycogen seen in many cells (see Fig. 20-2).
process (p. 292) . Agar is also used to form a surface for
the growth of bacterial colonies. Another commercial
Bacterial a n d Algal Cel l Wa lls Contain use of agar is for the capsules in which some vitamins
Structural Heteropolysaccha rides and drugs are packaged; the dried agar material dis­
solves readily in the stomach and is metabolically inert.
The rigid component of bacterial cell walls (peptidogly­
can) is a heteropolymer of alternating ({31�4) -linked Glycosaminoglycans Are H eteropolysaccharides
N-acetylglucosamine and N-acetylmmamic acid residues
of the Extracel l u lar Matrix
(see Fig. 20-31). The linear polymers lie side by side in
the cell wall, cross-linked by short peptides, the exact The extracellular space in the tissues of multicellular
structme of which depends on the bacterial species. The animals is filled with a gel-like material, the extracellu­
peptide cross-links weld the polysaccharide chains into a lar matrix (ECM) , also called ground substance ,
strong sheath that envelops the entire cell and prevents which holds the cells together and provides a porous
cellular swelling and lysis due to the osmotic entry of pathway for the diffusion of nutrients and oxygen
water. The enzyme lysozyme kills bacteria by hydrolyzing to individual cells. The reticular ECM that surrounds fi­
the ({3 1�4) glycosidic bond between N-acetylglucosa­ broblasts and other connective tissue cells is composed
mine and N-acetylmuramic acid (see Fig. 6-24) . of an interlocking meshwork of heteropolysaccharides
Lysozyme is notably present in tears, presumably as a de­ and fibrous proteins such as fibrillar collagens, elastin,
fense against bacterial infections of the eye. It is also pro­ and fibronectin. Basement membrane is a specialized
duced by certain bacterial viruses to ensme their release ECM that underlies epithelial cells; it consists of special­
from the host bacterial cell, an essential step of the viral ized collagens, 1aminin, and heteropolysaccharides.
infection cycle. Penicillin and related antibiotics kill bacte­ These heteropolysaccharides, the glycosaminogly­
ria by preventing synthesis of the cross-links, leaving the cans, are a family of linear polymers composed of
cell wall too weak to resist osmotic lysis (see pp. 216-21 7) . repeating disaccharide units (Fig. 7-22 ) . They are
Certain marine red algae, including some o f the sea­ unique to animals and bacteria and are not found in
weeds, have cell walls that contain agar, a mixture of plants. One of the two monosaccharides is always either
sulfated heteropolysaccharides made up of D-galactose N-acetylglucosamine or N-acetylgalactosamine; the
and an L-galactose derivative ether-linked between C-3 other is in most cases a uronic acid, usually D-glucuronic
and C-6. Agar is a complex mixture of polysaccharides, or L-iduronic acid. Some glycosaminoglycans contain es­
all with the same backbone structure , but substituted terified sulfate groups. The combination of sulfate
to varying degrees with sulfate and pyruvate. Agarose groups and the carboxylate groups of the uronic acid
CMr 150,000) is the agar component with the fewest
� residues gives glycosaminoglycans a very high density of
charged groups (sulfates, pyruvates) ( Fig. 7-2 1 ) . The negative charge. To minimize the repulsive forces among
remarkable gel-forming property of agarose makes it neighboring charged groups, these molecules assume an