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Carbohydrates
Chapter 8 - Fundamentals of Biochemistry
Donald Voet • Judith G. Voet • Charlotte W. Pratt

Compared to nucleotides or amino acids, carbs

are more simple, containing just three elements—
C, H, and O—combined according to the formula
(C H2O)n, where n ≥ 3.

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A Monosaccharides Are Aldoses or Ketoses

• Monosaccharides are aldehyde or ketone derivatives of straight-chain polyhydroxy alcohols

containing at least three carbon atoms.
• If the carbonyl group is an aldehyde, the sugar is an aldose
• If the carbonyl group is a ketone, the sugar is a ketose
• The smallest monosaccharides, those with three carbon atoms, are trioses.
• Those with four, five, six, seven, etc. C atoms are, respectively, tetroses, pentoses, hexoses,
heptoses, etc.

Ketone Aldehyde

Fischer Projection The L sugars are the mirror

images of their D counterparts.

Ketone aldehyde

D sugars have the same absolute

configuration at the asymmetric center
farthest from their carbonyl group as does
D-glyceraldehyde

Because L sugars are biologically much less abundant than D sugars, the D prefix is often omitted

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How many chiral centers?

Figure 8-1

How many possible isomers?

How about D-Glucose ?

How many chiral centers
and possible isomers
does it have?

Figure 8-1

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All but two of its six C atoms, C1 and

C6, are chiral centers,

so D-glucose is one of 24 = 16 possible

stereoisomers.

Chemical structures of aldohexose stereoisomers (Fischer projection). Notes: All, allose; Alt, altrose;
Glc, glucose; Man, mannose; Gul, gulose; Ido, idose; Gal, galactose; Tal, talose

DOI:10.1080/09168451.2016.1146069

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How about D-Ribulose ?

How many chiral centers
and possible isomers
does it have?

Figure 8-2 part 2

The position of their carbonyl

group gives ketoses one less
asymmetric center than their
isomeric aldoses, so a
ketohexose has only 23 = 8
possible stereoisomers (4 D
sugars and 4 L sugars).

How about ketopentose?

Figure 8-2 part 2

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What is Epimers ?

Sugars that differ only by the

configuration around one C atom
are known as epimers of one
another.
Thus, D-glucose and D-mannose are
epimers with respect to C2.

Alcohols react with the carbonyl groups of aldehydes and ketones to form hemiacetals
and hemiketals, respectively:

The hydroxyl and either the aldehyde or

the ketone functions of monosaccharides
can likewise react intramolecularly to
form cyclic hemiacetals and hemiketals

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Cyclization of glucose and fructose

A sugar with a six-membered ring is known as a pyranose

in analogy with pyran (at left), the simplest compound
containing such a ring.
Sugars with five-membered rings are designated
furanoses in analogy with furan (at right).

The cyclic forms of glucose and fructose with six- and five-
membered rings are therefore known as glucopyranose
and fructofuranose

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𝛂 and 𝛃 anomers. The monosaccharides α-D-glucopyranose and β-D-glucopyranose, drawn as

Haworth projections and ball-and-stick models, interconvert through the linear form. They differ
only by their configuration about the anomeric carbon, C1.

When a monosaccharide cyclizes, the carbonyl carbon, called the anomeric carbon, becomes
a chiral center with 2 possible configurations.
The pair of stereoisomers that differ in configuration at the anomeric carbon are called
anomers.

In the 𝛂 anomer, the OH substituent of the anomeric carbon is on the opposite side of the
sugar ring from the CH2OH group at the chiral center that designates the D or L configuration
(C5 in hexoses).
The other form is known as the 𝛃 anomer

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The two chair conformations of 𝛃-D-glucopyranose.

In the conformation on the left, which predominates, the relatively bulky OH and CH2OH
substituents all occupy equatorial positions, where they extend alternately above and
below the ring. In the conformation on the right (drawn in ball-and-stick form, right), the
bulky groups occupy the more crowded axial (vertical) positions

Sugars Can Be Modified and Covalently Linked

Oxidation of an aldose converts its aldehyde group to a

carboxylic acid group, thereby yielding an aldonic acid
such as gluconic acid (left).
Aldonic acids are named by appending the suffix -onic
acid to the root name of the parent aldose.

Oxidation of the primary alcohol group of aldoses yields uronic

acids, which are named by appending -uronic acid to the root
name of the parent aldose, for example, D-glucuronic acid (right).

Uronic acids can assume the pyranose, furanose, and linear forms.

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Sugars Can Be Modified and Covalently Linked

Aldoses and ketoses can be reduced under mild conditions—for example, by treatment with
NaBH4 Sodium borohydride—to yield polyhydroxy alcohols known as alditols, which are named
by appending the suffix -itol to the root name of the parent aldose.

Ribitol is a component of riboflavin (vit B2) & flavin mononucleotide (FMN)

Glycerol and the cyclic polyhydroxy alcohol myo-inositol are important lipid components
Xylitol is a sweetener that is used in “sugarless” gum and candies:

Sugars Can Be Modified and Covalently Linked

L-Fucose is one of the few L sugar

components of polysaccharides.

Monosaccharide units in which an OH group is replaced by H are known as deoxy sugars.

The biologically most important of these is 𝛃-D-2-deoxyribose, the sugar component of DNA’s
sugar–phosphate backbone

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Sugars Can Be Modified and Covalently Linked

In amino sugars, one or more OH groups have been

replaced by an amino group, which is often
acetylated.

D-Glucosamine and D-galactosamine (at left) are the

most common.

N-Acetylneuraminic acid is an important constituent of

glycoproteins and glycolipids

(proteins and lipids with covalently attached carbohydrate).

Sugars Can Be Modified and Covalently Linked

N-Acetylneuraminic acid, which is derived from N-acetylmannosamine and pyruvic acid

N-Acetylneuraminic acid and its derivatives are often referred to as sialic acids.

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Glycosidic Bonds Link the Anomeric Carbon to Other Compounds

The anomeric group of a sugar can condense with an alcohol to form 𝛂- and 𝛃-glycosides

The bond connecting the anomeric carbon to the alcohol oxygen is termed a glycosidic bond.

Formation of glycosides. The acid-catalyzed condensation of α-D-glucose with methanol yields an

anomeric pair of methyl-D-glucosides.

Glycosidic Bonds Link the Anomeric Carbon to Other Compounds

? N-Glycosidic bonds form between the

anomeric carbon and an amine.

Example: the bonds that link D-ribose to

purines and pyrimidines in nucleic acids

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Previous Slide…
Alcohols react with the carbonyl groups of aldehydes and ketones to form hemiacetals
and hemiketals, respectively:

The hydroxyl and either the aldehyde or

the ketone functions of monosaccharides
can likewise react intramolecularly to
form cyclic hemiacetals and hemiketals

Reducing sugars
CuO + H2 → Cu + H2O

Any sugar that is a reducing agent, cause reduction Cu is reduced, CuO is reducing agent
Because H2 is oxidized, H2 is reducing agent
It has a free aldehyde or a free ketone group

Monosaccharides with a hemiacetal are also reducing sugars, because

their open chain form contain an aldehyde

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Reducing sugars

Reducing sugars

Although fructose is a keto sugar, and ketones generally give a negative test
with the Benedict, there is an exception.

If the carbon adjacent to the ketone carbon (the “alpha carbon”) contains a
hydroxyl group, the ketone will be in equilibrium with an aldehyde through
tautomerization (called an “enediol rearrangement”)

Fructose is a reducing sugar as well

α-hydroxy ketones are in equilibrium with aldehydes through
tautomerization

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Reducing sugars

Reducing sugars

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Reducing sugars

Lactose and Maltose are also reducing

sugars & give a positive Benedict test

Reducing sugars

Sugars without hemiacetals are non-reducing sugars

Acetals are “locked” and not in equilibrium with a ring-opened form with an aldehyde
Therefore, they don’t react as a reducing agent

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Reducing sugars

Sugars without hemiacetals are non-reducing sugars

Acetals are “locked” and not in equilibrium with a ring-opened form with an aldehyde
Therefore, they don’t react as a reducing agent

Reducing sugars

Complex polysaccharides that only have a single hemiacetal unit don’t count as reducing sugar,
example : starch

Sugars are able to form long chains with each other in arrangements known as polysaccharides.
Common examples of polysaccharides are starch, cellulose, and glycogen.

The vast majority of individual sugar units in these polysaccharides are joined to each other via
acetal (“glycosidic“) linkages. Hemiacetals are present, but only at the termini of the polymer.

Starch, for example, generally has about 300-600 individual units of glucose, but only one unit
(the terminus) has a hemiacetal.

One hemiacetal “needle” in a haystack of “acetals” is not enough to give a positive test for
reducing sugars. Therefore these polysaccharides are not considered reducing sugars. For
example, starch gives a negative test

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O-β-Dgalactopyranosyl-(1→4)-D-glucopyranose

The systematic name for lactose, O-β-Dgalactopyranosyl-(1→4)-D-glucopyranose,

specifies its monosaccharides, their ring types, and how they are linked together.

The symbol (1→4) combined with the β in the prefix indicates that the glycosidic
bond links C1 of the β anomer of galactose to O4 of glucose

O-α-D-glucopyranosyl-(1→2)-β-D-fructofuranoside

The systematic name for sucrose, O-α-D-glucopyranosyl-(1→2)-β-D-fructofuranoside,

indicates that the anomeric carbon of each sugar (C1 in glucose and C2 in fructose)
participates in the glycosidic bond, and hence sucrose is not a reducing sugar.

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One of the oldest artifi cial sweeteners is

saccharin, discovered in 1879 and
commonly consumed as Sweet’N Low®.

In the 1970s, extremely high doses of saccharin were found to cause cancer in laboratory
rats.
Such doses are now considered to be so far outside of the range used for sweetening

Aspartame, the active ingredient in NutraSweet® and

Equal®, was approved for human use in 1981 and is
currently the market leader:

Unlike saccharin, which is not metabolized by the human

body, aspartame is broken down into its components:
aspartate (green), phenylalanine (red ), and methanol (blue).

The Asp and Phe, like all amino acids, can be metabolized, so aspartame is not calorie free.

Methanol in large amounts is toxic; however, the amount derived from an aspartame-sweetened drink
is comparable to the amount naturally present in the same volume of fruit juice.

Individuals with the genetic disease phenylketonuria, who are unable to metabolize phenylalanine, are
advised to avoid ingesting excess Phe in the form of aspartame (or any other polypeptide).

The greatest drawback of aspartame may be its instability to heat, which makes it unsuitable for baking

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Cellulose is a linear polymer of up to 15,000 D-glucose residues

linked by β(1→ 4) glycosidic bonds

Electron micrograph of cellulose

fibers. Picture: cell wall from the alga
Chaetomorpha are arranged in layers.

X-Ray & others → cellulose chains are flat ribbons in which successive
glucose rings are turned over 180° with respect to each other

This permits the C3—OH group of each glucose residue to form a hydrogen bond with the ring
oxygen (O5) of the next residue.
Parallel cellulose chains form sheets with interchain hydrogen bonds, including O2—H ∙∙∙ O6 and
O6—H ∙∙∙ O3 bonds

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Cellulose, the primary structural

component of plant cell walls

Chitin is a homopolymer of β(1→4)-

linked N-acetyl-D-glucosamine residues

It differs chemically from cellulose only in

that each C2—OH group is replaced by an
acetamido group

Chitin is the principal structural component of the exoskeletons of invertebrates such as crustaceans,
insects, and spiders and is also present in the cell walls of most fungi and many algae

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Starch is a mixture of glycans that plants synthesize

as their principal energy reserve.

It is deposited in the chloroplasts of plant cells as

insoluble granules composed of 𝛂-amylose and
amylopectin

α-Amylose is a linear polymer of several thousand

glucose residues linked by α(1→4) bonds.

Similar to cellulose

While cellulose’s β-glycosidic linkages cause it to

assume a tightly packed, fully extended conformation,
α-amylose’s α-glycosidic bonds cause it to adopt an
irregularly aggregating helically coiled conformation

Cellulose fibers consist of ± 40 parallel,

extended glycan chains. In the chain, each of α-Amylose forms a left-handed helix
the β (1→4)-linked glucose units is rotated
180o to its neighbor. Dashed lines represents
hydrogen bonds
What makes these two different?

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Amylopectin consists mainly of α(1→4)-linked glucose

residues but is a branched molecule with α(1→6) branch
points every 24 to 30 glucose residues on average.

Amylopectin molecules contain up to 106 glucose residues,

making them some of the largest molecules in nature.

The storage of glucose as starch greatly reduces the large intracellular osmotic pressure that
would result from its storage in monomeric form, because osmotic pressure is proportional to
the number of solute molecules in a given volume

Glycogen’s highly branched structure,

which has many nonreducing ends,
permits the rapid mobilization of glucose
in times of metabolic need.

The α(1→6) branches of glycogen are

cleaved by glycogen debranching enzyme

Figure 8-11

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The extracellular spaces, particularly those

of connective tissues such as cartilage,
tendon, skin, and blood vessel walls,
contain collagen and other proteins
embedded in a gel-like matrix that is
composed largely of glycosaminoglycans.

These unbranched polysaccharides consist

of alternating uronic acid and hexosamine
residues.

Solutions of glycosaminoglycans have a

slimy, mucuslike consistency that results
from their high viscosity and elasticity.

Hyaluronate Acts as a Shock Absorber and Lubricant.

Hyaluronic acid (hyaluronate) is an important

glycosaminoglycan component of connective tissue,
synovial fluid (the fluid that lubricates joints), and the
vitreous humor of the eye

In most mammals, hyaluronate molecules are composed of 80 to 8000 β(1→4)-linked

disaccharide units that consist of D-glucuronic acid and N-acetyl-D-glucosamine (GlcNAc) linked
by a β(1→3) bond

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Proteins and glycosaminoglycans in the extracellular matrix aggregate

covalently and noncovalently to form a diverse group of macromolecules
known as proteoglycans.

Proteoglycans have a bottlebrush-like molecular architecture, with

“bristles” noncovalently attached to a filamentous hyaluronate
“backbone.”
The bristles consist of a core protein
to which glycosaminoglycans, most
often chains of keratan sulfate and
chondroitin sulfate, are covalently
linked

The interaction between the core

protein and the hyaluronate is
stabilized by a link protein.

Smaller oligosaccharides are usually

attached to the core protein near its site of
attachment to hyaluronate.

These oligosaccharides are glycosidically

linked to the protein via the amide N of
specific Asn residues - and are therefore
known as N-linked oligosaccharides.

The keratan sulfate and chondroitin sulfate chains are glycosidically linked to the core protein
via oligosaccharides that are covalently bonded to side chain O atoms of specific Ser or Thr
residues (i.e., O-linked oligosaccharides).

The extended brushlike structure of proteoglycans, together with the polyanionic character of their
keratan sulfate and chondroitin sulfate components, cause these complexes to form highly
hydrated gels.

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Many eukaryote proteins are glycosylated

N-Glycosylation occurs cotranslationally

O-Linked oligosaccharides are synthesized in the Golgi apparatus by the serial addition of
monosaccharide units to a completed polypeptide chain

1)
An oligosaccharide containing
9 mannose residues,
3 glucose residues, and
2 GlcNAc residues
is attached to the Asn of a growing polypeptide
chain that is being synthesized by a ribosome
associated with the endoplasmic reticulum

2)
Some of the sugars are removed during processing, which begins
in the lumen (internal space) of the endoplasmic reticulum and
continues in the Golgi apparatus.

Enzymatic trimming is accomplished by glucosidases and

mannosidases.

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3)
Additional monosaccharide residues, including GlcNAc, galactose, fucose, and sialic acid, are
added by the action of specific glycosyltransferases in the Golgi apparatus.

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End of this topic

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