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Welcome to Class 7
Introductory Biochemistry
Class 7: Outline and Objectives
l  Monosaccharides
l  Aldoses, ketoses; hemiacetals; epimers
l  Pyranoses, furanoses
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
l  Bioenergetics: ATP and coupled reactions
l  Phosphoryl group transfers
l  Concentration dependence of ∆G
1
Monosaccharides
terminal carbon (C1) is carbonyl
(aldehyde)
second carbon (C2) is carbonyl
(ketone)
The most common monosaccharides
figure 7-1
Stereoisomers
of glyceraldehyde
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 7-2
2
D-aldoses (aldehydes)
The more commonly occurring aldoses are shown in red boxes
figure 7-3
D-ketoses (ketones)
(achiral)
figure 7-3
The more commonly occurring ketoses are shown in red boxes
3
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.
Although epimers are isomeric, they are not mirror images (enantiomers)
figure 7-4
and in general they have different chemical and physical properties.
Hemiacetals and hemiketals
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.
figure 7-5
4
Cyclic forms of monosaccharides
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
molecule. The reaction is freely reversible.
1%
A new asymmetric C atom
(anomeric carbon) is formed in
the process of forming a cyclic
hemiacetal, making two
isomeric forms (anomers)
possible, designated α and β.
33%
(at equilibrium)
66%
figure 7-6
The actual conformation of a pyranose ring
is not flat, but assumes a chair-like shape
D-Glucose is the aldose that
most commonly occurs in
nature as a monosaccharide.
figure 7-7, 7-8
5
Why more beta than alpha D-glucopyranose?
D-Glucopyranose adopts only one of the two
possible chair forms where all pyranose
substituents are arranged equatorially.
α-D-Glucopyranose has 4 equatorial and 1 axial
substitutions on the pyranose ring whereas β-DGlucopyranose has 5 equatorial substituents on
the pyranose ring. Minimization of steric hindrance
favors equatorial positions for the highest number
of pyranose substituents. The anomeric effect
involving stabilization of the axial configuration of
the hydroxyl group on the anomeric carbon
through molecular orbital overlap of the oxygen
lone pairs and the anomeric carbon bond with its
OH group is not enough to stabilize the alpha
form and therefore in the case of Dglucopyranose sterics trumps the anomeric
effect.
33%
66%
Haworth Perspectives of Cyclic Sugars
● 
Substituents that appear on the right side in Fischer projections are below
the plane of the ring in Haworth perspectives.
● 
If the hydroxyl group of anomeric carbon is on the same side of the ring as
the hyrdoxyl group of the highest numbered asymmetric carbon (e.g., C5
of a hexose), the anomer is defined as α (opposite side ≡ β anomer). But,
this is not always easy to see.
● 
A practical rule, which works for both D- and L-pyranoses and furanoses,
is that if the hydroxyl group on the anomeric carbon is trans to the terminal
CH2OH in the Haworth perspective drawing, the sugar is an α anomer; if it
is cis to the terminal CH2OH, it is a β anomer.
HO
α-D-Fructofuranose
2
α
5
4
1
3
HO
or
OH
α-D-Glucopyranose
H
β-D-Ribofuranose
2
H
OH
β
β
or
β
HO
β-D-Glucopyranose
6
Mutarotation
!  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
(aldehyde or ketone) form of the respective monosaccharide until
equilibrium between the two forms is reached. This is called
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.
Pyranoses and furanoses
Glucose: almost
exclusively pyranose
Fructose: 67% pyranose,
33% furanose
figure 7-7
7
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).
+ H2O
+ 3H+
figure 7-10
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.
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
+ 3H+
figure 7-10
8
Chemical oxidation products of glucose
figure 7-3
Blood glucose determination
Oxidized glucose (gluconate) has
a strong tendency to internally
esterify >> lactone formation. This
helps to drive the reaction by
lowering [product].
+ OH–
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 7-9
9
Oxidation at other carbons is more difficult, but
such oxidation products do occur in nature
C6
C1
(the oxidized carbon is shown in color)
figure 7-9
Hemiacetals and hemiketals can be esterified
with alcohols to form acetals and ketals
In contrast to hemiacetals and hemiketals,
acetals and ketals are relatively stable.
figure 7-5
10
Formation of the acetal disaccharide maltose
Formation of an acetal from
a hemiacetal and an alcohol
(hydroxyl group).
Dehydration
Wavy lines: Anomer not
specified (could be α or β)
O-glycosidic bond
figure 7-10
Common disaccharides
Reducing sugars have a free
anomeric carbon.
Non-reducing sugars have no
free anomeric carbons.
Non-reducing sugars are named
pyranosides or furanosides.
figure 7-11
11
Naming Conventions
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
or
β-D-fructofuranosyl α-D-glucopyranoside
Fru(β2↔1α)Glc
figure 7-11
α
O
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
Fru(β2↔1α)Glc(6→1α)Gal
Polysaccharides (glycans)
figure 7-12
12
Some polysaccharides
Glucose
l  Starch (plants)
l  Amylose: α1→4
l  Amylopectin: α1→4, α1→6
l  Glycogen (animals, bacteria): α1→4, α1→6
(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
Starch
Maltose
figure 7-13 a,b,c
13
Structure of starch
Starch granules
figure 7-19a,b
Starch
Maltose
figure 7-13a,b,c
What is the advantage of storing glucose as a polymer?
14
Starch
Maltose
figure 7-13a,b,c
What is the advantage of having only one reducing end?
Starch
Maltose
figure 7-13a,b,c
What is the advantage of having many non-reducing ends (branching)?
15
Cellulose
180° flip
Cellulose accounts for over
half of the carbon in the
biosphere.
The disaccharide unit of
cellulose is called cellobiose.
figure 7-14, 7-20
Chitin
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
group at C2, chitin is the next most abundant polysaccharide in the biosphere.
figure 7-16a
16
Peptidoglycans in
bacterial cell walls
Penicillin interferes with cell wall
formation by preventing the synthesis
of cross-links.
(Alexander Fleming)
figure 20-30
What is the advantage of having unusual (D-) amino acids?
Proteoglycans
(more carbohydrate than protein)
Glycosaminoglycans ≡ unbranched polysaccharides of alternating uronic acid
(oxidized at C6) and GlcNAc or GalNAc residues (often sulfated)
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 7-22
17
Glycoproteins
(more protein than carbohydrate)
GlcA-GlcNS
GlcA-GalNAc
Immunoglobin
Plasma membrane protein
Almost all secreted and membrane-associated
proteins of eukaryotic cells are glycosylated.
figures 5-22b, 7-26
Glycoproteins
(more protein than carbohydrate)
Immunoglobin
Almost all secreted and membrane-associated
proteins of eukaryotic cells are glycosylated.
Plasma membrane protein
figures 5-21b, 7-26
18
Glycoproteins
figure 7-30
What is the advantage of having so much potential variation?
Glycoproteins
19
Introduction to Bioenergetics
The equilibrium constant for a reaction,
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.
20
The actual ∆G of a reaction depends on reactant
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.
This is the case when
becomes negative ([C][D] < [A][B]), for
example when products C and D are constantly removed as soon as they are
formed.
Standard free energy changes are additive
If the two reactions can be effectively coupled, a reaction with a large
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
individual reactions A to B (1) and B to C (2).
21
Standard free energy changes are additive
Glucose + Pi → Glucose 6-P + H2O
ΔG' º = 13.8 kJ/mol
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.
Energy coupling
Example: glucose phosphorylation
Energy coupling occurs
through shared intermediates
(Pi in this case).
figure 1-27b
22
Nucleotides and nucleosides
Adenine
D-Ribose
Nucleoside
Nucleotide
= Nucleoside-P
Nucleoside-diP
Nucleoside-triP
Adenosine triphosphate (ATP)
Hydrolysis of the γ- and β-phosphates is highly exergonic.
γ
β
α
(phosphate groups are
usually complexed with Mg2+)
figures 1-26, 13-12
23
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
24
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
25
Energy released by hydrolysis of
biological phosphate compounds
figure 13-19
Hydrolysis of phosphocreatine
Phosphocreatine has a high phosphoryl group transfer potential.
It can drive the formation of ATP from ADP.
figure 13-15
26
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
27