Biomolecules

Chemical principles that are components and functions in

living organism.
Biomolecules that are the major
constituents of cells

Proteins: long polymers of amino

acids
Nucleic acids (DNA and RNA):
polymers of nucleotides
Polysaccharides: polymers of
simple sugars
Lipids: building from glycerol and
fatty acids
Stereospecificity of biomolecules is important to
catalytic functions.
•In living organisms, only one form of isomers of biomolecules
can be employed as components and functions.
•Proteins or enzymes can only bind to specific isomers,
D-isomer form of sugar or L-isomer form of amino acid.
•Compounds of carbon commonly exist as stereoisomers.
 Subdivision of isomers

Enantiomer
(chiral molecules)

Diasteroisomer
 Chirality
A chiral object has a mirror image that is different from the
original object (for not chiral, being called achiral)
Indicate whether the following objects are chiral or achiral.
 Enantiomers
A pair of enantiomers is always possible for molecules that
contain one tetrahedral atom with four different groups
attached to it.

Chiral molecules Achiral molecules

Behind the plane

C Upward out of the

plane
Line in the plane
Nomenclature of Enantiomers: The (R-S) System
Cahn-Ingold-Prelog system or (R-S) system

I Assign a priority of each

substitute group based on
atomic number

If can not make decision, use the next

Atoms along the chain as tiebreakers.
 Cahn-Ingold-Prelog system or (R-S) system

H 1 CH3 3 H 5
C Br C CH3 C CH3
H CH3 CH3

H 2 H 4 H 6
C Cl C CH2 F C CH3
Cl CH3 H

In case of double and triple bond, treat them as a single bond to

a separate atom.
 Nomenclature of enantiomers: the (R-S) System

II Rotate the formula so that the

group with lowest priority is directed
away from us.

III Draw an arrow from

first priority group,
through the second,
to third
Clockwise (R, rectus)
Counter clockwise (S, sinister)
Nomenclature of enantiomers: the (R-S) System
 Interactions between biomolecules are
stereospecificity.
•In living organism, chiral molecules are usually present in only
one from of their chiral forms.
•Glucose occurs biologically in the D isomer.
•Amino acids occur only as L isomer.

The ability to distinguish between stereoisomers is a properties

of enzymes and other proteins and a characteristics feature of
the molecular logic of life.
 Classification of carbohydrates
•The simplest carbohydrates are the monosaccharides

•Sugars or saccharides (Latin saccharum, Greek sakaron)

•General formula is (CH2O)n, carbohydrate-hydrates of carbon

•Carbohydrates are usually defined as polyhydroxy aldehydes

or polyhydroxy ketones
O O
Aldehyde group C C ketone group
H

Monosaccharides: the simplest carhohydrates

Disaccharides: monosaccharide + monosaccharide
Oligosaccharides: polymers of 2-10 monosaccharides
Polysaccharides: > 10 monosaccharides
 Classification of monosaccharides
Monosaccharides are classified according to
I The number of carbon atom (triose, tetrose, pentose)
II Group containing in molecules
Adehyde: aldose
Ketone: ketose

Combination of two classifications: aldotetrose, ketopentose

Enatiomers contain optical activity.

polarizer

Polarized light
Polarimeter is used to determine optically active
compounds.

Enantiomer that rotates the polarized light:

Clockwise (+), dextrorotatory (dexter = right)
Counterclockwise (-), levorotatory (laevus = left)
 Configuration and the plane-polarized light

-No correlation exists between configuration of enantiomers

and the direction (+ or -) of plane-polarized light.

-No necessary correlation exists between the (R) and (S) and
the direction (+ or -) of plane-polarized light.
 D and L designations of monosaccharides
The simplest monosaccharides are glyceraldehyde and
dihydroxyacetone

CHO CH2OH
CHOH HC O
CH2OH CH2OH

Glyceraldehyde Dihydroxyacetone R-S system:

(aldotriose) (ketotriose)
(+)-Glyceroldehyde is (R)
(-)-Glyceraldehyde is (S)

(+)-glyceraldehyde is designated D-(+)-glyceraldehyde and

(-)-glyceraldehyde is designated L-(-)-glyceraldehyde.

Both compounds serve as configurational standards for all

monosaccharides.
 D and L designations of monosaccharides
A momacharides whose the highest numbered stereocenter
(the penultimate carbon) has the same configuration as
D-(+)-glyceroldehyde is designated as a D sugar.

Draw vertically with ketone

or aldehyde group at or
nearest the top. D sugar is
designated when the hydroxyl
group is on the right.

D and L isomers are like (R) and (S) in that they are not related
to optical rotation because it is only one designed for the
penultimate carbon - that may encount other sugars that are
D-(+) or D-(-) and ones that are L-(+) or L-(-).
 Structural formulars for monosaccharides

Fischer projection

Emil Fischer
(1852-1919)
D-(+)-glucose primarily exists in equilibrium with
two cyclic forms.
The cyclic forms of D-(+)-glucose are hemiacetal
formed by an intramolecular reaction of the –OH
group at C5 with aldehyde group of C1.

Cyclic form

Linear form
The addition of alcohols: hemiacetals and acetals
Hemiacetal
An aldehyde or ketone in an alcohlol causes the slow of an
equilibrium establishment between these two compounds
and a new compound called a hemiacetal.

The hemicaetal is resulted from nucleophilic addition of the

alcohol oxygen to the carbonyl carbon of aldehyde or ketone.
The addition of alcohols: hemiacetals and acetals

Hemiacetal

Cyclic form of D-glucose

Ketone group of ketose undergo similar reaction in an alcohol

Hemiketal

Hemiketal
 Diastereoisomer of two cyclic forms

α β

α anomer: -OH is on the β anomer: -OH is on the

opposite side of the ring same side of the ring
from –CH2OH from –CH2OH

•Cyclization creates a new sterocenter at C1(diasteroisomer).

•In carbohydrate chemistry diasteroisomers of this type are
called anomers, and the hemiacetal carbon atom is called
anomeric carbon.
•Structure representing anomers are called Haworth formulas.
•Each anomer is designed as an α anomer and β anomer.
 The actual conformation of D-glucose
Studies of the structure of cyclic form of D-glucose using x-ray
crystallography have demonstrated that the rings are the chair
forms.

O Aldohexoses also exist in five-

membered ring. However, the
aldopyranose ring is much more
Pyran stable than the aldofuranose and
predominates in six-membered ring.
The six-member ring
O

Furan

The five-member ring

 Mutarotation
-OH axial -OH equatorial

-The concentration of open-chain D-glucose at equilibrium is

very small (negative test for Schiff’s reagent).

-β-anomer is more stable than α-anomer for D-glucose but this

is not necessary because with D-mannose, the equilibrium
favors the α-anomer.
 Monosaccharides are reducing agents.
•Benedict’s reagent (an alkaline solution containning a cupric
citrate complex ion) and Tollen’s solution [Ag(NH3)2OH] can
oxidize and give positive test with aldose and ketose.
•Sugars positive test are known as reducing sugars:
all carbohydrates that contain a hemiacetal group
give positive test
all carbohydrates that contain only acetal group do not give
positive test.

No equilibrium
in aldehydes
or α-hydroxy ketones
 Monosaccharides are reducing agents.
•Cu2+ can oxidize only aldose but in alkaline solution, ketose

convert to aldose.
•The oxidation only occurred in noncyclic forms but they are
still enough for reacting to alkaline copper solution and this
can perturb equilibrium to produce more Haldehydes or O
α-hydroxy ketones. CH2OH C OH C H
•Positive test provides C O OH- C OH OH- HC OH
brick-red precipitate (CHOH)n (CHOH)n (CHOH)n

O CH2OH CH2OH CH2OH CH2OH

CH Ketose
C O

(CHOH)n (CHOH)n Cu2+

or Cu2O + Oxidized Products
CH2OH CH2OH
Aldose Ketose
 Isomers of monosaccharides
-A molecule with n chiral centers can have 2n stereoisomers.
-Two isomer molecules that are not mirror images or not
enantiomer are called diastereoisomer.
-Two sugars that differ only in the configuration of one carbon
atom are called epimer. H O
C

H O H C OH
C
HO C H
H C OH
H C OH
CH2OH
H C OH
D-Glyceraldehyde CH2OH
21 isomers
D-Glucose
24 isomers
 Disaccharides
Disaccharides such as maltose, lactose and sucrose consist of
two monosaccharides covalently link by o-glycosidic bond.
•O-glycosidic bond is formed
by ahydroxyl group of one
sugar reacting with the
anomeric carbon of the other.
•This bond can be hydrolyzed
by acid but resist cleavage to
base.
•Anomeric carbon involving in
glycosidic bond can not be
oxidized by cupric or ferric ion
thus, in disaccharides or
polysacharides, the end of
chain be oxidized and called
reducing end
 Disaccharides

-occurs naturally in milk

Reducing sugars

Nonreducing sugars
-energy storage in hemolymph
of insect

-formed by plants but not animals

Nonreducing sugars
 Polysaccharides
•An another name is glycan.
•Polymers can be occurred with or without branching.
Two types of polysaccharides:
•homopolysaccharides contain only single type monomer.
-Food storage for monosaccharides, starch and glycogen
-Structural element, cellulose or plant cell wall and chitin for
exoskeleton
•heteropplysaccharides contain two or more different kinds.
-extracellular support (extracelluar matrix component) for
organism of all kingdom
homopolysaccharides heteropolysaccharides
 Polysaccharides
Strach (storage polysaccharide in plant)
-Two types
>Amylose: glucose polymer that D-glucose residues are
liked by α(1-4) linkages
>Amylopectin: similar to amylose but higher molecular
weight with branch points at α(1-6) linkages
Glyogen (storage polysaccharide in animal)
>Main storage in liver and skeletal muscle
>Structure is similar to amylopectin but more extensively
branched
 Polysaccharides
Structural conformation of starch or glycogen
 Polysaccharides
Dextran (bacterial and yeast polysaccharides)
•Polymer of D-glucose that are linked by α(1-6) with branching
at α(1-3) and some points at α(1-2) α(1-4)
•Dental plaque is composed of dextran produced by oral
bacteria on tooth surface.
Cellulose
•Structural component in plants, cell wall, trunk, woody portion
and stalks.
•Polymer of D-glucose in βconfiguration with β (1-4) linkages
•Most animals can not use cellulose as fuel source because
they have no enzymes to degrade bond of β (1-4)
 Polysaccharides
Structural conformation of dextran and cellulose

•Cellulose is extended structure

with lying side by side of several
chains.
•Structure is stabilized by interchain
and intra chain hydrogen bonds.
 Polysaccharides
Chitin
•linear chain of homopolysaccharide
•Polymer of N-acetylglucosamine linked by
β (1-4) configuration
•Animal enzymes can not hydrolyze chitin
•Component of hard skeleton in arthropod,
insects, lobsters and crabs
 Polysaccharides
Agar
•Natural products from marine red algae and some sea weeds
•Sulfated heteropolysaccharides of D-galactose and
L-galactose
•L-galactose has ether linkage between C3 and C6.
•Unbranched polymers: agarose
•Branched polymers: agaropectin
•Gel-forming properties
 Amino acids, peptides and three dimensional
of proteins
•Proteins are polymers of amino acids.
•All proteins are the combination of 20 amino acids in
differences of sequences resulting in differences of function
and properties.
General structure of amino acids
α carbon,
chiral center First carbom atom of
H carboxylic group, which is
deprotonated form at
+
H3N C COO- physiological pH

R
Amino group is Side chains which vary in
protonated structure, size and electric charge
at physiological pH.
 D and L forms of amino acids

•L-isomers of amino acids are remarkable found in living

organisms.
•D-amino acid residues can be found only in a few, small
peptides, bacterial cell walls and peptide antibiotics.
•Enzymes synthesizing amino acids in living organisms contain
asymmetric active sites and cause stereospecificity.
 Classification of amino acids according to
R group

Glycine has no
optical activity.
Classification of amino acids according to
R group
Classification of amino acids according to
R aroup
 Amphotoric properties of amino acids

Amino acids have a diprotic acid, monoamino and

monocarboxylic group (ampholyte).

Fully protonated Zwitterion Fully deprotonated

Priority in deprotonation of amino and carboxylic
group
Titration curve of amino acids
•At pH point of inflection
between two stages of
one positive charge group
and one negative charge
group results in no net
charge.

•The pH that affects on

both groups resulting in
No net charge is called
pI.

pK a = − log K a pK a1 + pK a 2
pI =
2
Titration curve of amino acids
In case of ionizable R group
 Peptides
•Protein is a polymer of amino acids covalently linked by
peptide bonds (amide bond).
•The direction of protein is
always indicate from N-ter
minus to C-terminus.
•N-terminal, C-terminal and
R group only distribute the
charge.

H3C CH3
CH
CH2OH H CH2 CH3 CH2
+
H H H H
H3N C C N C C N C C N C C N C C O-
H O H O H O H O H O

N-terminal (amino) C-terminal (carboxylic)

 Direction of peptides
•Find the position of peptide bond
•Imagine in the peptide bond cleavage and see on right side of
the end group whether it is amino or carboxylic
H3C CH3
CH
CH2OH H CH2 CH3 CH2
+
H H H H
H3N C C N C C N C C N C C N C C O-
H O H O H O H O H O

H3C CH3
CH
CH2 CH3 CH2 H CH2OH
-
H H H H
O C C N C C N C C N C C N C C NH3+
O H O H O H O H O H
 Peptide bond structures

•In x-ray crystallography studies, C-N is shorter than C-N bond

in simple amine.
•The atom of Cα, C-carbonyl group, N and –H are coplanar in
trans.
•This characteristics is come from resonance hybrid between
oxygen and N atom.
•C-N bond can not freely rotate whereas Cα-C and N-Cα are
permitted.
 Levels of protein structures
•Primary structure: the sequences of amino acid residues
•Secondary structure: stable arrangements of amino acid
residues forming specific patterns
•Tertiary structure: three dimensional arrangements of
specific patterns
•Quaternary structure: arrangements of polypeptide subunits
when a protein has more than one polypeptide
 Protein secondary structure
Helical structure (α-helix)
•Tightly wound polypeptide backbone in right handed direction
•R groups (side chains) protrude out from the helical backbone
•Structure is stabilized by intramolecular hydrogen bond between
C=O and N-H of polypeptide backbone.
N (+)

3.6 residues per turn

C (-)
Cross-section view
 Protein secondary structure
β conformation
•The backbone of polypeptides arrange similar to pleats
(β sheet) in zigzag pattern.
•The structure is stabilized by intermolecular hydrogen bond
of adjacent peptides (two-type arrangements, parallel and
antiparallel).
•R groups (side chains) protrude from zigzag conformation is
opposite directions.
More stable (shorter distance of H-bond)
 Protein tertiary structure

α+β

α helix β sheet
•Some proteins contain only helical, only sheet and combination

of both types of secondary structure.

•Three dimensional structure can be stabilized by weak
interactions such as hydrophobic, ionic interaction, hydrogen
bond, which are formed by side chain residues.
•The strong stabilization can be also formed by covalent linkage
of disufide bond (S-S) between cystein residues at different
positions in polypeptide.
Protein tertiary structure
 Quaternary structure
•Some proteins consist of more than one polypeptide chain,
called multisubunit.
•Individual subunit can be identical or different.
•Oligomer: different subunit, heterodimer, heterotetramer
•Protomer: identical subunit, homodimer, homotetramer
•Most of quaternary structures are stabilized by noncovalent
interaction: a few proteins that subunits are covalently linked
such as insulin

Hemoglobin:
subunit
heterotetramer (α2β2)