Class 7: Outline and Objectives

l  Monosaccharides
l  Aldoses, ketoses; hemiacetals; epimers
l  Pyranoses, furanoses
Welcome to Class 7 l  Mutarotation, anomers
l  Disaccharides and glycosidic bonds
l  Polysaccharides
l  Starch, glycogen, cellulose, chitin
l  Bacterial cell walls (peptidoglycans)
l  Glycoconjugates: Proteoglycans and glycoproteins

Introductory Biochemistry l  Bioenergetics: ATP and coupled reactions

l  Phosphoryl group transfers
l  Concentration dependence of ∆G

Monosaccharides Stereoisomers
of glyceraldehyde
terminal carbon (C1) is carbonyl
(aldehyde) second carbon (C2) is carbonyl
(ketone) Monosaccharides are chiral.
A molecule with n chiral centers can
have 2n possible stereoisomers.

The chiral center most distant from the

carbonyl carbon defines D- and L-forms.

L- and D- isomers of the same

compound are mirror images
(enantiomers).

Enantiomers of compounds with more

than one chiral center have all chiral
centers reversed.
figure 7-1 figure 7-2
The most common monosaccharides

1
 D-aldoses (aldehydes) D-ketoses (ketones)

(achiral)

figure 7-3
The more commonly occurring aldoses are shown in red boxes figure 7-3 The more commonly occurring ketoses are shown in red boxes

Hemiacetals and hemiketals

Epimers of Glucose

If two sugars differ only in the configuration around one
carbon atom, they are called epimers.
D-Mannose and D-Galactose are both epimers of D-Glucose.
D-Mannose and D-Galactose are not epimers of one another.
Hemiacetals and hemiketals are molecules with hydroxyl and ether groups
on the same carbon. They result from the reaction between aldehyde or keto
groups and alcohol. The reaction is freely reversible.

Although epimers are isomeric, they are not mirror images (enantiomers) figure 7-5
and in general they have different chemical and physical properties. figure 7-4

2
 Cyclic forms of monosaccharides The actual conformation of a pyranose ring
is not flat, but assumes a chair-like shape
Monosaccharides contain both aldehyde or
keto groups and hydroxyl groups. In aqueous
solutions, most monosaccharides occur as
cyclic structures. They result from hemiacetal
or hemiketal formation between aldehyde or
keto groups and hydroxyl groups on the same
1% molecule. The reaction is freely reversible.

A new asymmetric C atom

(anomeric carbon) is formed in
the process of forming a cyclic D-Glucose is the aldose that
hemiacetal, making two most commonly occurs in
isomeric forms (anomers) nature as a monosaccharide.
possible, designated α and β.

33% (at equilibrium) 66% figure 7-6 figure 7-7, 7-8

Why more beta than alpha D-glucopyranose? Haworth Perspectives of Cyclic Sugars
●  Substituents that appear on the right side in Fischer projections are below
D-Glucopyranose adopts only one of the two the plane of the ring in Haworth perspectives.
possible chair forms where all pyranose ●  If the hydroxyl group of anomeric carbon is on the same side of the ring as
substituents are arranged equatorially. the hyrdoxyl group of the highest numbered asymmetric carbon (e.g., C5
α-D-Glucopyranose has 4 equatorial and 1 axial of a hexose), the anomer is defined as α (opposite side ≡ β anomer). But,
substitutions on the pyranose ring whereas β-D- this is not always easy to see.
Glucopyranose has 5 equatorial substituents on ●  A practical rule, which works for both D- and L-pyranoses and furanoses,
the pyranose ring. Minimization of steric hindrance 33% is that if the hydroxyl group on the anomeric carbon is trans to the terminal
favors equatorial positions for the highest number CH2OH in the Haworth perspective drawing, the sugar is an α anomer; if it
of pyranose substituents. The anomeric effect is cis to the terminal CH2OH, it is a β anomer.
involving stabilization of the axial configuration of 5
the hydroxyl group on the anomeric carbon HO
α-D-Fructo- 4 1 β
β-D-Ribo-
2 α
through molecular orbital overlap of the oxygen furanose furanose
lone pairs and the anomeric carbon bond with its 3 2

OH group is not enough to stabilize the alpha

form and therefore in the case of D-
HO OH H
glucopyranose sterics trumps the anomeric 66% or β or β
effect. OH H HO

α-D-Glucopyranose β-D-Glucopyranose

3
 Mutarotation Pyranoses and furanoses

!  Although anomers are isomeric, they are not mirror images

(enantiomers). In general, they have different physical and
chemical properties. Anomers rotate polarized light differently.

!  Interconversion between α and β anomers occurs via the linear

Glucose: almost
(aldehyde or ketone) form of the respective monosaccharide until exclusively pyranose Fructose: 67% pyranose,
equilibrium between the two forms is reached. This is called 33% furanose

mutarotation. Their equilibrium ratio need not be 1:1! Because

anomers rotate polarized light differently, the optical rotation of
the solution changes in the process.

!  At equilibrium, the linear (aldose or ketose) form is present only

in minute amounts.

figure 7-7

Sugars as reducing agents Sugars as reducing agents

Hemiacetals are easily converted to aldehydes;
aldehydes are easily oxidized to acids. The oxidation of the aldehyde involves
transfer of two electrons to an acceptor, which becomes reduced.
Therefore, monosaccharides are reducing sugars. (Ketones, as well as aldehydes,
react with oxidants, but ketones react more slowly, and the products of ketose
oxidation include glycolaldehyde, derived from C1 and C2).
Hemiacetals are easily converted to aldehydes;
aldehydes are easily oxidized to acids. The oxidation of the aldehyde involves
transfer of two electrons to an acceptor, which becomes reduced.
Therefore, monosaccharides are reducing sugars.
Reducing sugars can be detected in solution by adding some colorless substance,
such as AgNO3, which is reduced to a colored product, such as Ag↓.

+ H2O + H2O

+ 3H+ + 3H+

figure 7-10 figure 7-10

4
 Chemical oxidation products of glucose
Blood glucose determination

Oxidized glucose (gluconate) has

a strong tendency to internally + OH–
esterify >> lactone formation. This
helps to drive the reaction by
lowering [product].

Assay: a peroxidase reaction uses the H2O2

produced by glucose oxidase to convert a
colorless compound into a colored one, which
absorbs light at a particular wavelength.

figure 7-3 figure 7-9

Oxidation at other carbons is more difficult, but Hemiacetals and hemiketals can be esterified
such oxidation products do occur in nature
with alcohols to form acetals and ketals

C6

C1

(the oxidized carbon is shown in color)

In contrast to hemiacetals and hemiketals,
acetals and ketals are relatively stable.
figure 7-9 figure 7-5

5
 Formation of the acetal disaccharide maltose Common disaccharides

Reducing sugars have a free

anomeric carbon.
Formation of an acetal from
a hemiacetal and an alcohol
(hydroxyl group).
Dehydration Non-reducing sugars have no
free anomeric carbons.
Wavy lines: Anomer not
specified (could be α or β)

Non-reducing sugars are named

pyranosides or furanosides.

O-glycosidic bond
figure 7-10 figure 7-11

Naming Conventions Polysaccharides (glycans)

Reducing oligosaccharides are

named ending with the sugar that
has the reducing anomeric carbon .

Non-reducing oligosaccarides
can be named beginning from
either end sugar.

H
α
or
O
β-D-fructofuranosyl α-D-glucopyranoside
Fru(β2↔1α)Glc

Raffinose
α-D-galactopyranosyl-(1→6)-α-D-glucopyranosyl β-D-fructofuranoside
Gal(α1→6)Glc(α1↔2β)Fru
or
β-D-fructofuranosyl α-D-glucopyranosyl-(6→1)-α-D-galactopyranoside figure 7-12
figure 7-11 Fru(β2↔1α)Glc(6→1α)Gal

6
 Some polysaccharides
Starch

l  Starch (plants)
l  Amylose: α1→4
l  Amylopectin: α1→4, α1→6
Glucose
l  Glycogen (animals, bacteria): α1→4, α1→6 Maltose
(more branched than starch)
l  Cellulose: β1→4

Starch and cellulose both consist of recurring units of D-glucose.

Their different properties result from different types of glycosidic linkage.

l  Peptidoglycans (bacterial cell walls)

l  Chitin (exoskeletons, cell walls): N-acetyl-D-glucosamine β1→4

figure 7-13 a,b,c

Structure of starch Starch

Maltose

Starch granules

figure 7-13a,b,c
figure 7-19a,b
What is the advantage of storing glucose as a polymer?

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 Starch Starch

Maltose Maltose

figure 7-13a,b,c figure 7-13a,b,c

What is the advantage of having only one reducing end? What is the advantage of having many non-reducing ends (branching)?

Chitin
Cellulose

180° flip
Cellulose accounts for over
half of the carbon in the
biosphere.

The disaccharide unit of

cellulose is called cellobiose.
N-acetyl-D-glucosamine: β1→4

Chitin is the principal structural component of the exoskeletons of arthropods

(crustaceans, insects, and spiders) and is present in the cell walls of fungi and
some algae. After cellulose, from which it only differs in the acetylated amino
figure 7-14, 7-20 group at C2, chitin is the next most abundant polysaccharide in the biosphere.
figure 7-16a

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 Peptidoglycans in Proteoglycans
bacterial cell walls (more carbohydrate than protein)

Glycosaminoglycans ≡ unbranched polysaccharides of alternating uronic acid

(oxidized at C6) and GlcNAc or GalNAc residues (often sulfated)

Penicillin interferes with cell wall

formation by preventing the synthesis
of cross-links.
(Alexander Fleming)

Core proteins + covalently linked glycosaminoglycans ≡ proteoglycans

Proteoglycans form the ground substance of connective tissue

(cartilage, tendon, skin, blood vessel walls). They have a slimy, mucuslike
consistency.
figure 20-30 figure 7-22
What is the advantage of having unusual (D-) amino acids?

Glycoproteins Glycoproteins
(more protein than carbohydrate) (more protein than carbohydrate)

GlcA-GlcNS

GlcA-GalNAc

Immunoglobin Plasma membrane protein Immunoglobin Plasma membrane protein

Almost all secreted and membrane-associated Almost all secreted and membrane-associated
proteins of eukaryotic cells are glycosylated. figures 5-22b, 7-26 proteins of eukaryotic cells are glycosylated. figures 5-21b, 7-26

9
 Glycoproteins
Glycoproteins

figure 7-30
What is the advantage of having so much potential variation?

The equilibrium constant for a reaction,

Introduction to Bioenergetics K'eq, is mathematically related to ∆G' º

A+B C+D

Standard free energy change (1 M concentrations, etc.):

[C][D]
=
[A][B]

[A], [B], [C], [D] are the molar concentrations of the

reaction components at equilibrium.

If [C][D] > [A][B] at equilibrium, then lnK'eq is positive, and therefore ∆G' º is
negative. This means if initially all reactants are present at 1 M concentration,
the reaction would go from A + B to C + D before and until equilibrium is
reached.

10
 The actual ∆G of a reaction depends on reactant Standard free energy changes are additive
and product concentrations as well as ∆G'º

A+B C+D

If the reactants are initially present not at 1 M, but at different concentrations

(nonstandard conditions):

The criterion for the direction of net spontaneous reaction is ∆G, not ∆G' º.

A reaction with a positive ∆G' º can go forward as long as ∆G is negative.

If the two reactions can be effectively coupled, a reaction with a large
This is the case when becomes negative ([C][D] < [A][B]), for negative ∆G' º can “drive” a reaction with a positive ∆G' º.

The pathway in a coupled reaction from A to C is different from the

example when products C and D are constantly removed as soon as they are
individual reactions A to B (1) and B to C (2).
formed.

Standard free energy changes are additive Energy coupling

Example: glucose phosphorylation

Energy coupling occurs

Glucose + Pi → Glucose 6-P + H2O ΔG' º = 13.8 kJ/mol through shared intermediates
(Pi in this case).
ATP + H2O → ADP + Pi ΔG' º = –30.5 kJ/mol

Glucose + ATP → ADP + Glucose 6-P ΔG' º = –16.7 kJ/mol

Glucose phosphorylation with Pi is endergonic.

ATP hydrolysis to ADP and Pi is highly exergonic.
ATP hydrolysis coupled to glucose phosphorylation is exergonic.

figure 1-27b

11
Nucleotides and nucleosides Adenosine triphosphate (ATP)

Hydrolysis of the γ- and β-phosphates is highly exergonic.

Adenine

γ β α

D-Ribose

Nucleoside
(phosphate groups are
Nucleotide usually complexed with Mg2+)
= Nucleoside-P
Nucleoside-diP
figures 1-26, 13-12
Nucleoside-triP

ATP hydrolysis

Pi ≡ inorganic phosphate

Factors favoring hydrolysis:

1.  Relief of electrostatic repulsion
2.  Pi is stabilized by resonance
3.  Mass action favors hydrolysis
(high [H2O])

figure 13-11

12
In intact cells, ∆G for ATP hydrolysis is often much more negative
than ∆G' º (—30.5 kJ/mol), ranging from —50 to —65 kJ/mol. This
is because [ATP]/[ADP][Pi] > 1.0 in cells

Energy released by hydrolysis of

biological phosphate compounds Hydrolysis of phosphocreatine

Phosphocreatine has a high phosphoryl group transfer potential.

It can drive the formation of ATP from ADP.

figure 13-19 figure 13-15

13
ATP can provide energy by group transfer
even when there is no net transfer of P
Derivation of energy from ATP hydrolysis
generally involves covalent
participation of ATP in the reaction.

Formation of glutamine by
condensation of glutamate with NH3
is endergonic (positive ΔG' º).

Formation of γ-glutamyl P by transfer

of P from ATP is exergonic (negative
ΔG' º).

Formation of glutamine by
displacement of P from γ-glutamyl P
by NH3 is exergonic (negative ΔG' º).

The net coupled reaction is

exergonic (negative ΔG' º).
figure 13-18

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