Chirality of

Biochemical Molecules

Focuses of our Project

Enzyme-Substrate Relationships
Effects on Tastes and Odors
Pharmaceutical Applications
As Seen in Living Organisms

Introduction: What is Chirality?

Introduction: What is Chirality?

The geometric property of a molecule being

non-superimposable on its mirror image; nonsuperimposable is not being able to place over
or something.
When an atom has four non-equivalent atoms or
groups attached to it, this is termed as the
chirality center.

Introduction: What is Chirality?

Two Stereoisomers that differ only in their
chirality = the arrangement of four different
atoms or groups attached to a center atom
typically a carbon, are called enantiomers.
Enantiomers are designated as R or S to signify
whether they have a right-handed (R) or lefthanded (S) configuration.
Active Learning: How do you determine if this
molecule is the R-enantiomer or the S-enantiomer?

Introduction: What is Chirality?

Molecules that portray chirality or handedness may
also be referred to as
Levorotary (L=counterclockwise) or
Dextrorotary (D=clockwise).
The L-configuration corresponds to the Senantiomer while the D-configuration corresponds
to the R-enantiomer.
This notation is often used to denote the
chirality of many common biochemical molecules
such as D-Fructose or L-Glyceraldehyde.

Introduction:

When is a Molecule Achiral?

A molecule is achiral (non-chiral) if
and only if it has an axis of
improper rotation, that is, an n-fold
rotation (rotation by 360/n)
followed by a reflection in the plane
perpendicular to this axis maps the
molecule on to itself.

Introduction:
Guidelines for Chirality
You can determine if a molecule is chiral or
achiral based on symmetry.
On the above model, you had a chiral reactant
binding to a chiral reactant site where everything
fits into place.
On the next model however, the enantiomer of the
reactant below will not bind to the enzyme, so it
will not react.
This leads to substrate specificity.

Enzyme-Substrate Relationships

Enzyme-Substrate Relationships
Enzymes
Macromolecules, mostly of protein nature,
that function as (bio) catalysts by
increasing the reaction rates. In general,
an enzyme catalyses only one reaction type
(reaction specificity) and operates on only
one type of substrate.

Enzyme-Substrate Relationships

Substrate
In an enzymatic reaction a substrate is the
specific biochemical molecule that is acted
upon by the enzyme to yield a specific
product.

Enzyme-Substrate Relationships

Substrate Specificity
A characteristic feature of enzyme activity
in relation to the kind of substrate on
which the enzyme or catalytic molecule
reacts.

Effects on Tastes and Odors

CHIRALITY AND ODOR

Effects on Tastes and Odors

WHAT ACCOUNTS A DIFFERENCE IN ODOR PERCEPTION?
The affect of chirality on bioactivity results in a
variation in odor.
Each enantiomer has a different 3-D fit on odor receptors in
the nose.
This phenomenon of specificity is not unlike that of enzymesubstrate relations.
The influence of this characteristic not only effects the
specific odor, but also intensity of odor.
Note: Bioactivity is defined as: The effect of a given agent,
such as a vaccine, upon a living organism or on living tissue.

Effects on Tastes and Odors

Why Do Lemons and Oranges Smell Differently?

Effects on Tastes and Odors

Why Do Lemons and Oranges Smell Differently?

Found in both orange and lemon peels,

Limonene is the molecule that is responsible for
their characteristic odors.
Oranges contain the left-handed molecule, and lemons, the
right-handed.
The same way your left foot fits only your left shoe, these
molecules fit only into the appropriate left or right-handed
receptors in your nose.
This is how the same molecule can cause the orange
and the lemon to have different smells.

Effects on Tastes and Odors

Enantiomers of Limonene

S-Limonene

R-Limonene

Effects on Tastes and Odors

Caraway

Spearmint

Effects on Tastes and Odors

Carvone
Carvone is a ketone that can be found in caraway,
dill, and spearmint oils.
These oils are used for flavoring liqueurs and in
perfumes and soaps.
(S)-carvone is
odor, while its
has a spearmint

a molecule with a caraway-like

mirror image molecule, (R)-carvone
odor.

Effects on Tastes and Odors

Enantiomers of Carvone

Effects on Tastes and Odors

Chirality and Food Flavor

Effects on Tastes and Odors

WHAT ACCOUNTS FOR FOOD FLAVOR?
The major components of the food we eat, amino
acids, proteins, carbohydrates, triacylglycerols
and some vitamins, are all chiral.
This has a major impact on the perceived taste.
Chiral compounds can even be used to determine a
products age, storage and handling procedures, and
whether or not the food is of natural or synthetic
origin.

Effects on Tastes and Odors

Aspartame Molecule

Effects on Tastes and Odors

Aspartame is a sugar substitute composed of
aspartic acid and phenylalanine.
Found in Equal and Nutrasweet,
aspartame is very low in
calories compared to
sucrose (table sugar).
Although it is
100-200x sweeter
than sugar, its
stereoisomer is bitter.

Effects on Tastes and Odors

FAST FACTS
There are more than 285 enantiomeric pairs (570
enantiomers) that are known to demonstrate odor
differences or odor intensity differences.
Until the mid-1970s to 1980s, the idea that optical
enantiomers could have different odors was not generally
accepted by academics.
8-10% of the population cannot distinguish between Rcarvone and S-carvone.
In 1848, French scientist, Louis Pasteur, discovered the
chirality in the spin of molecules while examining salt of
tartaric acid.

Pharmaceutical Applications
Chirality and Pharmaceutical Drugs
Most drugs derived from natural sources are chiral
and are almost always obtained as a single
enantiomer whereas approximately 80% of
synthesized drugs are composed of a 50:50 racemic
mixture.
Receptors and enzymes in the body are very stereo
selective and only react with one of the
enantiomers of a chiral molecule in a process
called chiral recognition
As
on
an

a result, one enantiomer has the desired effect

the body, while the other may have no effect or
adverse effect.

Pharmaceutical Applications
In Vivo Effect of Enantiomers
Both enantiomers exhibit similar therapeutic
properties (e.g. Promet-hazine, Flecainide)
Only one isomer shows pharmacological activity (Spropranolol is a beta blocker) while the other one
is inactive (R-propranolol)
One type of isomer may show one type of
pharmacological activity (S-penicillamine) and the
other one shows toxicity (R-penicillamine)
One type of isomer may show one type of
pharmacological activity (R- methylphenylpropyl
barbituric acid anesthetic) and the other type
shows a convulsant effect

Pharmaceutical Applications

Thalidomide - C13H10N2O4

Pharmaceutical Applications
Thalidomide
Drug that was used in Europe during the period
1959 1962 to combat morning sickness in
pregnant women.
( R ) thalidomide contained the properties that
made it useful as a sedative and antinausea drug.
( S ) thalidomide was responsible for many
birth defects such as phocomelia.
Even if thalidomide were purified to only the
R- isomer, the pH of blood would cause rapid
racemization into roughly equal amounts of both
isomers.

Pharmaceutical Applications
Birth Defects Caused by Thalidomide

Thalidomide Babies

Pharmaceutical Applications
Enantiomers of Th
alidomide

'S' Optical isomer

'R' Optical Isomer

Pharmaceutical Applications
Advantages of using the more
active isomer of a drug
It leads to opportunities for racemic switching
Increase in production capacity
Less waste
Dose will be halved
Less likelihood of side effects

As seen in living organisms

The Chirality of biochemical molecules greatly
affects their functions in living organisms.
Many Organisms can use only the D-configuration or
the L-configuration of a specific molecule.
A specific enantiomer may be produced by one
organism and passed on to another for further use.
Many major biochemical molecules present even in
our own bodies are chiral.
Typically in nature

As seen in living organisms

Monosaccharide are found in the D-configuration

D-Galactose
D-Glucose
In what foods would
you find these
monosaccharide?

As seen in living organisms

D-Galactose is commonly referred to as milk sugar
because it is found in dairy products such as
milk, cheese and yogurt.
D-Glucose is found in a wide variety of foods from
vegetables to baked goods.
D-Glucose molecules are synthesized by plants to
store energy collected from the sun through the
reactions of photosynthesis.
The D-Glucose we consume is oxidized within our
cells to release this stored energy as heat and
ATP.

As seen in living organisms

While Amino Acids are found in the L-Conformation

L-Cysteine
L-Serine

What Amino Acid is

Achiral?

As seen in living organisms

The Amino Acid
Glycine is Achiral
because it has
2 Hydrogen atoms
attached to its
central Carbon
Atom.

As seen in living organisms

A major exception to the generalization that amino
acids in nature exist in the L-Configuration is
found in the cell walls of bacteria
Bacterial cell walls are consist of a
Peptidoglycan layer.
The Peptidoglycan layer is made up of chains of
the sugar units NAM (N-acetylmuramic acid) and NAG
(N-acetylglucosamine).
Amino acids are attached to the NAM units and are
cross linked together between the sugar unit
chains.

As seen in living organisms

Diagram of Gram-Negative Bacterial Cell Wall

As seen in living organisms

In Gram-Positive Bacteria the Peptidoglycan layer
is very thick.
The 4th Amino Acid
the 3rd Amino Acid
or by a bridge of

in each chain is cross-linked to

in the adjacent chain directly
multiple amino acids.

The amino acids attached to the NAM units in the

NAG-NAM chains are: 1) L-Alanine
2) D-Glutamic Acid
3) L-Lysine
4) D-Alanine

As seen in living organisms

Amino Acid Bridge in Cell Wall of Gram Positive Bacteria

As seen in living organisms

In
is
to

Gram-Negative Bacteria the Peptidoglycan layer

not as thick, but an outer membrane is present
help protect the cell.

The cell walls of Gram-Negative Bacteria differ in

their amino acid chains in the 3rd position there
is Meso-Diaminopimelic acid (DAP) instead of the
L-Lysine found in Gram-Positive.
The Peptidoglycan layers of Gram Negative Bacteria
also lack interpeptide bridges; their amino acid
chains are connected by direct bonding between the
3rd and 4th amino acids only.

As seen in living organisms

Direct Amino Acid linkages in Gram-Negative Bacteria

Conclusion:

Active Learning

3.* (1996 F 4) Vitamin E is a fat soluble vitamin

essential for muscle development. Two Chemistry 32
students take Vitamin E; Fred gets his vitamin from a
discount drug store; Sara believes in "natural foods
and so she buys her Vitamin E from a health food
store. Freds Vitamin E is made in a factory; Saras
Vitamin E is derived from soybeans. Fred and Sara
compared their Vitamin E samples by taking a melting
point and measuring the 1H NMR spectrum of each.
The melting points are different!!

Conclusion:

Active Learning

A. What is the difference between Fred and

Sara's samples?
B. What additional experiment would clarify
the difference between Fred and Sara's
Vitamin E?
C. Would the NMR spectra of the two samples
be the same?
D. What do you advise Fred and Sara about
taking the synthetic versus natural Vitamin
E?

Conclusion:

Active Learning

A. What is the difference between Fred and Sara's

samples?
Natural compounds, such as Sara's sample, occur as
one enantiomer. Vitamin E has 3 chiral centers, so
there are 23=8 possible stereoisomers, many of which
are probably contained in the synthetic analog that
Fred bought.

Conclusion:

Active Learning

B. What additional experiment would clarify

the difference between Fred and Sara's
Vitamin E?
Because Fred's sample is a mixture of
diastereomers and Sara's sample is one pure
enantiomer, the samples will have different
physical and light-rotating properties.
Chromatography or solubility experiments could
clarify the differences in physical properties.
NMR might elucidate how the structures differ.
In addition, the optical activity of the
samples could be checked. (Fred's sample is
probably racemic.)

Conclusion:

Active Learning

C. Would the NMR spectra of the two

samples be the same?
They would be different. Fred's NMR would
be complex because he has a mixture of
diastereomers, which would be present in
unpredictable ratios; Sara's would be
simpler.

Conclusion:

Active Learning

D. What do you advise Fred and Sara about

taking the synthetic versus natural
Vitamin E?
Biological receptors are often stereospecific,
so only the proper enantiomer would be
effective. Fred's Vitamin E probably has only
1/8 of the proper compound and probably
contains other diastereomers that may be
harmful. Sara's Vitamin E is a pure sample of
the proper, natural compound and would be well
received in the body.

For More Information see

(References)

Carey, Francis A. Organic Chemistry. 5th ed. New

York: McGraw-Hill, 2000
Dr. Gilmers Chapter 19 lecture
EXPERIMENT # 3: Essential Oils (EO). EO-1.
MASSACHUSETTS INSTITUTE OF TECHNOLOGY Department
of Chemistry. 5.310 Laboratory Chemistry.
EXPERIMENT #3 ESSENTIAL OILS.
http://web.mit.edu/5.310/www/Essential_oils.pdf
http://en.wikipedia.org/wiki/Image:D-glucose.png
http://en.wikipedia.org/wiki/Image:D-galactose_Fis
cher.png
http://orion.math.iastate.edu/mathnight/activities
/modules/Mirror/leftpanel.pdf
http://web.mit.edu/5.310/www/Essential_oils.pdf

For More Information see

(References)
http://www.alislam.org/library/books/revelation/pa
rt_5_section_6.html
http://www.answersingenesis.org/docs/3991.asp
http://www.arches.uga.edu/~kristenc/cellwall.html
http://www.chemie.fuberlin.de/chemistry/bio/aminoacid/cystein_en.html
http://www.chemie.fuberlin.de/chemistry/bio/aminoacid/serin_en.html
http://www.chm.bris.ac.uk/motm/thalidomide/start.h
tml
http://www.chm.bris.ac.uk/motm/thalidomide/optical
2iso.html
http://www.factsandcomparisons.com/assets/advinpha
rm/AIP_1-3_242-252.PDF
http://www.geocities.com/pribond/bioinfo/glossary/
pharmabio.htm

For More Information see

(References)

http://www.google.com/search?
q=cache:yNHjdf5_NpMJ:www.dissolutiontech.com/DTres
our/0803art/DT0803art2.pdf+chirality+in+pharmacy+d
rugs&hl=en
http://www.leffingwell.com/download/chiralityphamacology.pdf
http://www.leffingwell.com/chirality/chirality.htm
http://www.roycastle.co.uk/gal_6/devon-foods.jpg
http://www.scri.sari.ac.uk/SCRI/Web/Site/home/Rese
archAreas/Theme2~GenestoProducts/QHN/External/Chir
ality.asp
http://www.tock.com/chem32/ste1/
Ghuysen, J.-M., Kakenbeck, R. New Comprehensive
Biochemistry: Bacterial Cell Wall (Volume 27).
New York, 1994. ElsevierScience B.V.

For More Information see

(References)
Inouye, Masayori. Bacterial Outer
Membranes: Biogenesis and Functions. New
York, 1979. John Wiley &Sons, Inc.
What is chirality?.
http://chirality.ouvaton.org/homepage.htm