Acetylcholinesterase normal function

In normal circumstances, acetylcholine is hydrolyzed almost immediately by acetylcholinesterase close to receptors in the synaptic cleft at sites of action (see Bowman, 1993). The normal function of acetylcholinesterase is to hydrolyze acetylcholine in the synaptic cleft, parasympathetic effector organ or neuromuscular junction, in order to terminate... 

FIGURE 3.4 Mechanism of action of acetylcholinesterase inhibition (A) Structure of AChE (B) normal functioning of AChE (C) inhibition of AChE by nerve agent sarin. (Adapted from Somani et al. )... 

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. 

The major action resulting from human exposure to diazinon is the inhibition of cholinesterase activity (refer to Section 2.4 for discussion). Two pools of cholinesterases are present in human blood acetylcholinesterase in erythrocytes and serum cholinesterase (sometimes referred to as pseudocholinesterase or butyrlcholinesterase) in plasma. Acetylcholinesterase, present in human erythrocytes, is identical to the enzyme present in neural tissue (the target of diazinon action) while serum cholinesterase has no known physiological function. Inhibition of both forms of cholinesterase have been associated with exposure to diazinon in humans and animals (Coye et al. 1987 Edson and Noakes 1960 Soliman et al. 1982). Inhibition of erythrocyte, serum, or whole blood cholinesterase may be used as a marker of exposure to diazinon. However, cholinesterase inhibition is a common action of anticholinesterase compounds such as organophosphates (which include diazinon) and carbamates. In addition, a wide variation in normal cholinesterase values exists in the general population, and there are no studies which report a quantitative... 

Q6 Cholinesterase inhibitors block the action of the enzyme acetylcholinesterase (which normally hydrolyses acetylcholine) and so terminate its activity. These drugs increase the life of released acetylcholine at the synapse, leading to an enhancement of acetylcholine activity. Drug treatment for Alzheimer s disease is supervised in specialist clinics where the patient s cognitive function can be assessed at approximately three-monthly intervals. About half the patients treated show a decreased rate of cognitive decline while receiving this type of drug. 

There are different types of cholinesterases in the human body, which differ in their location in tissues, substrate affinity, and physiological function. The principal ones are acetylcholinesterase (AchE, EC 3.1.1.7), found in the nervous system and also present in the outer membrane of red blood cells, and plasma cholinesterases (EC 3.1.1.8, ChE), which are a group of enzymes present in plasma, liver, cerebrospinal fluid, and glial cells. Under normal physiological conditions, AChE performs the breakdown of acetylcholine (ACh), which is the chemical mediator... 

Acetylcholine is an essential neurotransmitter that affects parasympathetic synapses (autonomic and CNS), sympathetic preganglionic synapses, and the neuromuscular junction (see also prior section on Toxic Syndromes). Hydrolysis of acetylcholine by acetylcholinesterase, which is present in nerve tissue, normally Limits the duration of action of this neurotransmitter and allows for normal synaptic function. Organophosphate (e.g., Malathion, Parathion, Diazinon,... 

Acetylcholine is an important neurotransmitter, which is essential to complete the transmission of neural impulses from one neuron (fibers that convey impulses to the nerve cell) to another. Without acetylcholine, the body cannot function normally. When a message is sent from the brain for a muscle to move or some other bodily function to activate, acetylcholine is released. It then binds to the postsynaptic membrane, which starts and continues the movement or action. When it is time for the movement to stop, acetylcholinesterase is released to remove the acetylcholine from the synapse, so it can be used again. 

Nerve agents attack enzymes in the body, and it is this that makes them so deadly. The enzyme that is key to normal autonomic functions as well as muscular contraction (and subsequent relaxation) is acetylcholinesterase (AChE). This enzyme, upon contact with acetylcholine, a key neurotransmitter, normally will cleave off acetic acid to form choline, returning the muscle fiber to... 

After the transmitter has induced a new electrical signal in the post-junctional membrane, it is essential that it be quickly removed so that its action is not prolonged. In nature, this removal is effected by one of the most efficient enzyme mechanisms known. The enzyme used is acetylcholinesterase (AChE) the actions of which are shown in Fig. 6.5a. AChE is contained in the folds of the post-junctional membrane but is synthesised in the liver. It is widespread around the body and is found in red cells from which the levels can be easily analysed. Analysis within synapses is more difficult and not possible in a normal clinical context. AChE exists in parallel with another cholinesterase, butyryl-cholinesterase (BuChE) which is equally widespread through the nervous system but whose functions are less well known than AChE. BuChE is important practically in the metabolism of certain drugs, notably the muscle relaxant suxamethonium which is used widely in anaesthesia for rapid intubation. 

D. Antiacetylcholinesterase Neurotoxins. The fourth type of neurotoxin is the one that binds to acetylcholinesterase (Rodriquez-Ithurralde et al., 1981 Cervenansky et al., 1991). When acetylcholinesterase is not functioning, acetylcholine (after binding to the acetylcholine receptor) cannot be hydrolyzed consequently, normal nerve transmission is impaired. Acetylcholinesterase action of D. angusticeps venom was first reported by Ro-driguez-Ithurralde et al. (1983). 

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