Nerve Toxins Destroyed by Plant-Derived Bioscavenging Molecules
November 25, 2010 10:01 AM
Transgenic Tobacco plant
(Source: The Biodesign Institute at Arizona State University)
Bioscavenging molecule BChE hunts and kills (or neutralizes) harmful organophosphates like pesticides, preventing them from harming the body
Arizona State University
biochemist has found that a chemical compound found in the brain, called acetylcholine, can be protected from poisoning from pesticides or nerve agents by creating a bioscavenging molecule synthetically from plants.
Tsafrir Mor, a biochemist in the Center for Infectious Diseases and Vaccinology at the Biodesign Institute at Arizona State University, has discovered that a bioscavenging molecule called butyrylcholinesterase (BChE) is capable of defending acetylcholine against deliberate or accidental poisoning from chemicals found in pesticides as well as nerve agents.
has several lines of communication buzzing around all the time via electrical impulses and chemical transmissions, sending messages across the clefts dividing neurons from one another, or neurons from target cells. Within this organized communication is acetylcholine, a neurotransmitter in the peripheral nervous system and central nervous system that is vital when it comes to proper function within both systems. The problem with acetylcholine is that its cholinergic design is an easy target for organophosphates, which are chemicals found in several different pesticides and nerve agents. Organophosphates tend to
either deliberately or accidentally.
Prior to Mor's research, treatment for pesticide poisoning consisted of chemicals like atropine. Atropine is capable of relieving symptoms and saving lives, but it cannot cure seizures, muscle weakness or other forms of long term neurological effects caused by pesticides.
But now, Mor has found that two types of bioscavengers are capable of defending the body and mind against organophosphates. The first is acetylcholinesterase (AChE), which is created from by neurons in the brain, and the second is BChE, which is created by the liver and circulates in blood serum. These bioscavengers bind with foreign, harmful substances and then destroys or neutralizes them.
In addition to destroying/neutralizing foreign substances, these cholinesterases also remove acetylcholine molecules after their signaling tasks are complete. If they didn't do this, the acetylcholine molecules would crowd the nervous system producing neuromuscular paralysis. This would eventually lead to death because an abundance of acetylcholine molecules would create unregulated muscle contraction leading to cardiac and respiratory collapse.
The cholinesterases clean up the completed acetylcholine molecules through hydrolysis, which is a chemical reaction where a molecule is split into two parts because of the addition of a water molecule. AChE is capable of hydrolyzing 25,000 molecules of acetylcholine per second.
While AChE provides a means of eliminating acetylcholine molecules, BChE lies in the blood waiting to destroy any anti-cholinesterases, which attempt to block cholinesterase agents. Plants mainly develop these anti-cholinesterases as a way of halting harmful insects that may eat them, using the "cholinergic matrix" for defensive and offensive purposes. But BChE neutralizes organophosphates effectively within mammals and birds, protecting acetylcholine from pesticide poisoning.
But acquiring BChE is a difficult challenge. While it can be extracted easily enough from blood, there just isn't enough to defend "a few thousand troops" from poisoning. So Mor has suggested using transgenic tobacco plants that are
modified to synthesize human BChE
in their leaves. After testing this on two animal models, Mor concluded that this method successfully protected them from pesticide and nerve agent organophosphate poisoning. In addition, Mor was able to extend the half-life of this plant-derived BChE, which heightened its effectiveness.
Mor notes that BChE could be used to gain a better understanding of acetylcholine-related
such as Alzheimer's disease. Also, BChE could be used to treat cocaine overdose, and could help patients who have a difficult time recovering from anesthesia after surgery because they lack the naturally occurring enzyme.
was published in
Proceedings of the National Academy of Sciences
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