Nerve agents enzymes

Pralidoxime improves the patient s muscle strength by removing the nerve agent from acetylcholinesterase. The acetylcholinesterase, when freed from the nerve agent, then resumes breakdown of acetylcholine. Pralidoxime s effectiveness decreases with time, because the enzyme/nerve agent complex can age and form an irreversible bond. The time course for this depends on the specific agent and can vary from minutes to hours. 

Cheng T-C, JJ Calomiris (1996) A cloned bacterial enzyme for nerve agent decontamination. Enz Microbiol Technol 18 597-601. 

Cheng T-C, SP Harvey, GL Chen (1996) Cloning and expression of a gene encoding a bacterial enzyme for decontamination of organophosphorus nerve agents and nucleotide sequence of the enzyme. Appl Environ Microbiol 62 1636-1641. 

Both the G- and V-agents have the same physiological action on humans. They are potent inhibitors of the enzyme acetylcholinesterase (AChE), which is required for the function of many nerves and muscles in nearly every multicellular animal. Normally, AChE prevents the accumulation of acetylcholine after its release in the nervous system. Acetylcholine plays a vital role in stimulating voluntary muscles and nerve endings of the autonomic nervous system and many structures within the CNS. Thus, nerve agents that are cholinesterase inhibitors permit acetylcholine to accumulate at those sites, mimicking the effects of a massive release of acetylcholine. The major effects will be on skeletal muscles, parasympathetic end organs, and the CNS. 

P. Mulchandani, A. Mulchandani, I. Kaneva, and W. Chen, Biosensor for direct determination of orga-nophosphate nerve agents. 1. Potentiometric enzyme electrode. Biosens. Bioelectron. 14, 77-85 (1999). 

P. Mulchandani, W. Chen, and A. Mulchandani, Flow injection amperometric enzyme biosensor for direct determination of organophosphate nerve agents. Environ. Sci. Technol. 35, 2562-2565 (2001). 

Presently available methods to diagnose and biomonitor exposure to anticholinesterases, e.g., nerve agents, rely mostly on measurement of residual enzyme activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in blood. More specific methods involve analysis of the intact poison or its degradation products in blood and/or urine. These approaches have serious drawbacks. Measurement of cholinesterase inhibition in blood does not identify the anticholinesterase and does not provide reliable evidence for exposure at inhibition levels less than 20 %. The intact poison and its degradation products can only be measured shortly after exposure. Moreover, the degradation products of pesticides may enter the body as such upon ingestion of food products containing these products. 

Field First Aid Nerve agents are the most toxic of the known chemical warfare agents. Chemically similar to organophosphate pesticides, their method of acting is to inhibit acetylcholinesterase enzymes. Individuals whose skin or clothing is contaminated with... 

Acetylcholinesterase An enzyme that hydrolyzes the neurotransmitter acetylcholine. The action of this enzyme is inhibited by nerve agents. 

Nerve Agent Substances that interfere with the central nervous system. Organic esters of phosphoric acid used as a chemical warfare agent because of their extreme toxicity (tabun-GA, sarin-GB, soman-GD, GF, and VX). All are potent inhibitors of the enzyme, acetylcholinesterase, which is responsible for the degradation of the neurotransmitter, acetylcholine in neuronal synapses or myoneural junctions. Nerve agents are readily absorbed by inhalation and/or through intact skin. 

While nerve agents vary in molecular structure, they all exert the same physiological effect on the body an increase in acetylcholine throughout the body caused by interference with a vital enzyme known as cholinesterase. The four primary nerve agents are tabun, sarin, soman, and VX. 

The potential use of foams has also been demonstrated for the decontamination of nerve agents [80]. In these applications, the detoxification of the nerve agent was carried out by immobilizing the enzyme organophosphorous acid anhydrase within either a fire fighting or blast-containment foam carrier. 

M. M. Benning, J. M. Kuo, F. M. Raushel, H. M. Holden, Three-Dimensional Structure of Phosphodiesterase An Enzyme Capable of Detoxifying Organophosphate Nerve Agents , Biochemistry 1994, 33, 15001-15007. 

Even more reactive towards acetylcholinesterase are the organophosphorus derivatives developed as chemical warfare nerve agents, e.g. sarin. Such compounds react readily with the enzyme and form very stable addition intermediates. It is unusual to see fluoride as a leaving group, as in sarin, but its presence provides a huge inductive effect, thus accelerating the initial nucleophilic addition step (see also Section 13.7). 

Nerve agents Highly toxic and potentially lethal chemical agents that affect the human nervous system by inhibiting the enzyme that aids the transmission of nerve impulses. Causes blurred vision, weeping, nausea, vomiting, urinary incontinence, respiratory distress, and reduced mental capability by attacking the nervous system. 

Enzyme Stabilization in Nanostructured Materials, for Use in Organophosphorus Nerve Agent Detoxification and Prophylaxis... 

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