Transcript Organophosphate

Alan Yanahan
CPSC 270, 2009
Malathion
An Organophosphate
History




1820s: investigations into
organophosphate (OP) chemistry began
Early 1900s: several OP compounds
synthesized
1930s: toxicity of OPs becoming
recognized
1940s: insecticidal action observed by
Germany during WWII
Organophosphates and
Germany

Group led by Gerhard Schrader
searching for substitutes to
nicotine as an insecticide


Nicotine in short supply during WWII
Developed a number of incredibly toxic
nerve agents
Sarin
Soman
Tabun
Organophosphates and
Germany

Schrader’s group also created some of
the first commercial OP insecticides
TEPP
Dimefox
Parathion
Schradan
After WWII

Schrader’s research records were
captured by Allied forces

Led to massive increase in interest in OP
insecticides

Early OPs



very effective against insects
Much more toxic to vertebrates than organochlorine
insecticides
Nonpersistent and chemically unstable
Malathion



First produced by American Cyanamid in 1950
Very safe
due to its
low vertebrate
toxicity
Used on
most fruits,
vegetables and
forage crops

Works on a wide range of insect pests
Malathion and the
Mediterranean Fruit Fly

The Mediterranean fruit
fly (Medfly) is an
invasive pest species
from the Mediterranean
area


Detrimental to many fruit
crops including citrus
Appeared in Los Angeles
and parts of Florida and
Texas on multiple
occasions

Outbreaks eradicated
each time
Malathion and the
Mediterranean Fruit Fly

Malathion used in the eradication
programs

Mixed with a bait of molasses and yeast


Sprayed from helicopters over the infested and
surrounding areas
Both male and female medflies that are drawn
to the bait feed on the insecticide and die
How Does Malathion Work?
Have to understand the nervous
system first
The Nervous System


Nerve cells transmit
messages from one
another by means of
electrical impulses
(action potentials)
The axon carries the
message away from
one nerve cell to the
dendrites of another
nerve cell
The Nervous System


Between the axon
and dendrite is a
gap referred to as
the synapse
In order for the
electrical message
to cross the
synapse, it must be
converted into a
chemical message
The Nervous System


When an electrical impulse
reaches the end of an axon, it
leads to the release of
chemicals called
neurotransmitters
These neurotransmitters bind
with receptors on the
dendrites of neighboring nerve
cells to cause the generation
of another electrical impulse

Enzymes break down
neurotransmitters to prevent
nerve cells from repeatedly firing
What Does This Look Like?
Axon of preVoltage gated
synaptic
cell
Ca2+ channel
receives action
closes
potential and
voltage gated
Ca2+ channel
opens
Vesicle releases
Acetylcholine binds
acetylcholine
with the enzymeinto
(neurotransmitter)
acetylcholinesterase
nerve
synapse
Acetylcholine
Vesicle
Na+
Na+
Ca2+
Choline is
released
Na+
Ca2+
Acetylcholine
Calcium is
ions
Nicotinic
acetylcholine
Ca2+ released
(Ca2+
from
) enter
nicotinic
axon
receptor opens
acetylcholine receptor
Acetate is released
Nicotinic
Sodium ions
acetylcholine
(Na+) enter
Acetylcholine binds with
receptor
the dendrite
closes
and cause
receptor (nicotinic
an action potential in
acetylcholine receptor)
post-synaptic cell
Reaction of Acetylcholine with
Acetylcholinesterase
Acetylcholinesterase

The job of acetylcholinesterase is to
break down acetylcholine into choline
and acetate


This prevents the generation of multiple,
unnecessary action potentials in postsynaptic cells
It contains an active site


This is where acetylcholine binds
Consists of two regions
The Active Site of
Acetylcholinesterase

An esteratic
site


An anionic site

Serine
Tyrosine
Aspartic Acid
Tryptophan
The amino
acid serine
The amino
acids Tyrosine
(3 of them),
Aspartic Acid,
and
Tryptophan
Reaction Mechanism
O
H
H
Acetylcholine
–
O
CH3
H3 C
H3 C
N+
H3 C
CH3
N+
O
O
O
N
H
O
Anionic Site
R2
R1
-
R2
N
H
-
CH3
O
R1
–
CH3
H3 C
O
CH3
H3 C
HO
Serine
-
Choline
–
O
O
-
O
O
OH
–
- O
R1
H
R2
Serine
H
Acetate
O
Anionic Site
O
H3 C
H
O
H
HH
O
H3 C
OH
H3 C
N
H
CH3
N+
O
O
R2
R1
N
H
O
R2
R1
N
H
O
-
–
H
When Malathion is Present in
the Synapse

Malathion mimics the molecular shape
of acetylcholine

Acetylcholinesterase tries to cleave it, but a
portion of the malathion molecule remains
bound to the protein

Acetylcholine can no longer be broken down so
nerves continue to fire

Leads to tremors, convulsions, paralysis, and death
in insects
What Does This Look Like?
The rest
This
time,ofmalathion
the
binds withremains
molecule
acetylcholinesterase
bound
to
acetylcholinesterase
making it unable to
function properly
Ca2+
Ca2+
Ca2+
Acetylcholine
is no longer
broken down,
Malathion
so
it is free to
bind again and
again with its
receptor to
cause multiple
action
potentials
Acetylcholine is
released
from nicotinic
Only a portion
of the
acetylcholine
receptor
malathion molecule
is released from
acetylcholinesterase
Na+
Na+
Na+
Nicotinic acetylcholine
receptor closes
Reaction Mechanism
Malathion
O
CH3
O
CH3
O
–
P
S
H3 C
O
–
O
H3 C
CH3
O
O
O
P
S
O
O
CH3
O
O
-
R2
R1
N
H
H
S
O
H3 C
H
O
S
H3 C
O
R2
R1
N
H
Anionic Site
Anionic Site
O
O
Serine
S
H3 C
H3 C
O
O
P
CH3
O
O
–
O
-
R2
R1
N
H
O
Anionic Site
H
S
O
O
CH3
O
H
Sources




Johnson, G., Moore, S.W. Current Pharmaceutical
Design. 2006, vol. 12, number 2, pages 217-225.
Kreiger, Robert I. Handbook of Pesticide Toxicology
2nd Edition: Agents. Chambers, Howard W., Boone, J.
Scott, Carr, Russell L., Chambers, Janice E. Chapter
44—Chemistry of Organophosphorous Insecticides.
San Diego: Academic Press, 2001.
Silverthorn, Dee Unglaub. Human Physiology An
Integrated Approach 4th Edition. San Francisco:
Pearson Education Inc., 2007.
Ware W., George. Pesticides Theory and Application.
New York: W.H. Freeman and Company, 1978.