Background to answer question: Thomas is a member of the armed forces and has be
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Question
Background to answer question:
Thomas is a member of the armed forces and has been issued a simple hypodermic injection device. He is instructed to take the device with him into battlefield situations and to inject himself with the device whenever it appears that nerve gas is being used. The device injects a solution containing a mixture of two compounds: atropine and HI-6.
Nerve gases (or nerve “agents”) are actually oils that are aerosolized by an explosive charge to form a cloud of liquid droplets containing the nerve agent. These aerosols are inhaled and absorbed into the bloodstream. These nerve agents are very potent acetylcholinesterase (AChE) inhibitors. They accentuate acetylcholine synaptic signals by interfering with the termination step of acetylcholine function.
Life-threatening symptoms of nerve gas poisoning include constriction of the airways (bronchoconstriction) and increased fluid secretion in the airways. Both effects result from excess ACh in the synaptic cleft of the parasympathetic axons that control these functions. Similarly, excess ACh at the neuromuscular junctions causes uncontrolled skeletal muscle contractions, which can interfere with breathing movements.
To understand why atropine and HI-6 are effective antidotes for nerve gas poisoning, you must look at the normal molecular interactions of ACh at the synapse, how toxic nerve agents affect those interactions, and how these antidote compounds reverse the toxic effects.
The AChE active site has two adjacent regions. One region binds the amino group of ACh. The other region has a hydroxy group that breaks the bond between acetate and choline and forms an ester bond with the acetyl group of the ACh. The choline part of the ACh molecule is released, but the ester-bonded acetate remains attached to the enzyme active site. Shortly thereafter (about 40 microseconds under normal conditions), the ester bond is hydrolyzed, and the acetate is released, leaving a free active site to undergo another reaction cycle. (This is how AChE normally works!)
Nerve agents are organophosphate compounds that bind to the active site of AChE through the same type of bonding as ACh. However, instead of forming an acetate ester, they form a phosphate ester. This phosphate ester is hydrolyzed very slowly. In fact, it can take several hours or days to hydrolyze the ester and "regenerate" the active AChE enzyme.
HI-6 has an amino group and a reactive group that fits in the AChE active site. When HI-6 binds to the phosphate-poisoned enzyme, the reactive group of HI-6 reacts with the phosphorus of the phosphate ester linkage, and the entire compound (along with the organophosphate) leaves. In other words, it cleaves the phosphate compound so that the AChE enzyme is “regenerated” or “active” once again.
Atropine is a muscarinic receptor antagonist that reverses the effects of excessive ACh at parasympathetic synapses. Recall that, in the autonomic nervous systems, efferent fibers consist of two neurons in a series; the synapse is found in ganglia outside of the CNS. In parasympathetic synapses, the post-synaptic membranes have muscarinic receptors.
Questions:
1) It is important that the soldier inject himself at the first sign of nerve gas exposure. Why? What could happen to him if he waited?
2) Atropine reverses the nerve gas-induced airway constriction and secretion, but has no effect on skeletal muscle contraction. Why not? (Hint: think about the different types of ACh receptors and where they are located.)
3) Assuming a person survives nerve gas poisoning, the inactive enzyme would eventually be replaced by newly synthesized AChE. Until the new AChE is synthesized, would the person still suffer symptoms of nerve gas poisoning?
4) Would new AChE be synthesized by the pre-synaptic or post-synaptic cell?
Explanation / Answer
Yes it is important because Initial symptoms following exposure to nerve agents (like sarin) are a runny nose, tightness in the chest, and constriction of the pupils. Soon after, the victim will then have difficulty breathing and will experience nausea and drooling. As the victim continues to lose control of their bodily functions, they will involuntarily salivate, lacrimate, urinate, defecate, and experience gastrointestinal pain and vomiting. Blisters and burning of the eyes and/or lungs may also occur.This phase is followed by initially myoclonic jerks followed by status epilepticus. Death then comes via complete respiratory depression, most likely via the excessive peripheral activity at the neuromuscular junction of the diaphragm.
2-Because atropine is not a nicotinic receptor inhibitor,
4- yes AChE will be synthesized because atropine is a reversible inhibitor
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