malathion an organophosphate alan yanahan cpsc 270, 2009
TRANSCRIPT
Malathion
An Organophosphate
Alan YanahanCPSC 270, 2009
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
Schradan
Dimefox
Parathion
TEPP
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 vertebratetoxicity
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?
Ca2+
Ca2+
Ca2+
Na+Na+
Na+
Axon of pre-synaptic cell receives action potential and voltage gated Ca2+ channel opens
Calcium ions (Ca2+) enter axon
Voltage gated Ca2+ channel closes
Vesicle releases acetylcholine (neurotransmitter) into nerve synapse
Acetylcholine
Vesicle
Acetylcholine binds with receptor (nicotinic acetylcholine receptor)
Nicotinic acetylcholine receptor opens
Sodium ions (Na+) enter the dendrite and cause an action potential in post-synaptic cell
Acetylcholine is released from nicotinic acetylcholine receptor
Nicotinic acetylcholine receptor closes
Acetylcholine binds with the enzyme acetylcholinesterase
Choline is released
Acetate is released
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 post-synaptic cells
It contains an active site This is where acetylcholine binds Consists of two regions
The Active Site of Acetylcholinesterase
An esteratic site The amino
acid serine An anionic site
The amino acids Tyrosine (3 of them), Aspartic Acid, and Tryptophan
Serine Tyrosine Aspartic Acid Tryptophan
Reaction Mechanism
H3C O
O
N+ CH3
CH3H
3C
Acetylcholine
Serine
Anionic Site-
ONH
O–
R2R1
H3C O
O–
N+ CH3
CH3H
3C
ONH
O
R2R1
-
O
HH
HON+ CH
3
CH3H
3C
Choline
-
-
H3C
O
ONH
O
R2R1
O–
HH3C
O–
ONH
O
R2R1
O HH
H
-
O
HHH3C
O
OH
O
NH
OH
R2R1
Acetate
O–
H- - --
Anionic SiteSerine
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?
Ca2+
Ca2+
Ca2+
Na+Na+
Na+
Acetylcholine is released from nicotinic acetylcholine receptor
Nicotinic acetylcholine receptor closes
This time, malathion binds with acetylcholinesterase
Only a portion of the malathion molecule is released from acetylcholinesterase
The rest of the molecule remains bound to acetylcholinesterase making it unable to function properly
Acetylcholine is no longer broken down, so it is free to bind again and again with its receptor to cause multiple action potentials
Malathion
Reaction Mechanism
Serine
-
ONH
O–
R2R1
-
P
SO
O
H3C
H3C
S
O CH3O
O CH3O
Malathion
-
P
S–
O
O
H3C
H3C
S
O CH3O
O CH3O
NH
R2R1
O
O
Anionic Site-
Anionic Site
S
O CH3O
O CH3O
H
O
H H
P
SO
O
H3C
H3C
NH
R2R1
O
O O–
H--
Anionic Site
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.