Enzymes acetylcholine esterase

Trettnak W., Reininger F., Zinterl E., Wolfbeis O.S., Fiber Optic Remote Detection of Pesticides and Related Inhibitors of the Enzyme Acetylcholine Esterase, Sensor Actuat B-Chem 1993 11 87. 

Like in the parasympathetic and ganglionic neurotransmission, the eliminating enzyme acetylcholine esterase is present at the postsynaptical membrane where it very efficiently reduces the free concentration of the transmitter. 

Enzymatic techniques have also been employed in the analysis of these compounds. The toxicity of carbamate insecticides is due to the inhibition of the enzyme acetylcholine esterase, so the determination of these compounds can be achieved by enzyme inhibition (2,83,119), bioassay (118,167), or enzyme-linked immunosorbent assay (ELISA) (168-171). In the detection of carbamates by fluorimetric enzyme inhibition, the effluent from a reversed-phase chromatographic column was incubated with cholinesterase, which was introduced via a postcolumn reagent delivery pump. Then, the resulting partially inhibited cholinesterase was reacted with N-methyl indoyl acetate to produce a fluorophore and a reduction in the baseline fluorescence (172). 

In addition to hydrogen ions, other species can also affect the enzymatic catalytic activity. This phenomenon is called inhibition it may be specific, nonspecific, reversible, or irreversible. The inhibition reactions can also be used for the sensing of inhibitors. The best-known example is the sensor for detection of nerve gases. These compounds inhibit the hydrolysis of the acetylcholine ester which is catalyzed by the enzyme acetylcholine esterase. Acetylcholine ester is a key component in the neurotransmission mechanism. 

Both steps of the process are catalyzed by the basic form of the imidazole group of a histidine residue forming part of the active site. If the native conformation of the enzyme is disrupted by denaturation reagents such as urea, the unique seryl hydroxyl loses its characteristic reactivity in both the acylation and the deacylation process (15). This is easily understood if we realize that the reactive serine and the catalytically active histidine are extremely far from one another along the polypeptide chain, being separated by 137 amino acid residues (16) they are brought into the necessary juxtaposition only by the specific folding in the native enzyme structure. The mechanism by which the enzyme acetylcholine esterase catalyzes the hydrolysis of its substrate acetylcholine appears to be very similar (17). As we shall see, a number... 

Enzymes Acetylcholine Esterase Organophosphorus and carbamic compounds Neurotoxicity... 

Acetylcholine esterase-catalyzed hydrolyses have been reported only for a small number of prochiral diacetates (Table 11.1-8). However, several of secondary monoacetates, which are valuable synthetic building blocks, have been obtained with high enantioselectivity (2-6 and 11) by using this enzyme. Acetylcholine esterase should be considered for the hydrolysis of diacetates which are not substrates for lipases and pig liver esterase. 

Acetylcholine vesicles fuse with the presynaptic membrane at a low rate to release their packets of transmitter even in the absence of nerve action potentials. This spontaneous release is random. It is insufficient to trigger an action potential in the muscle but can cause a small depolarisation of the membrane, termed a miniature endplate potential The smallest depolarisation is caused by release of the contents of a single vesicle, or one quantum of acetylcholine. After release the synaptic vesicle membrane is rapidly taken up into the nerve terminal and reutilised. The acetylcholine is broken down in the cleft to acetate and choline in a reaction catalysed by the enzyme acetylcholine esterase which resides in the neuromuscular cleft and the choline is taken back up into the nerve terminal where it participates in the synthesis of new transmitter. 

Figure 4. Acetylcholine is released from the postsy naptic receptors and is immediately destroyed by the enzyme, acetylcholine esterase. This prevents an acetylcholine molecule initiating more than one depolarisation. The wave of depolarisation speeds off down the nerve cell membrane.

Transmission of nervous impulses by way of acetylcholine release and action is widespread, occurring not only in higher animals but also important in arthropods. In higher animals acetylcholine is the most important neurohormonal transmitter. It functions in the autonomic system, in motor nerves, and in some parts of the central nervous system. It functions not only in synapses between neurons but also on muscles or glands that are controlled by the neurons. After its action the acetylcholine is removed rapidly through hydrolysis by the enzyme acetylcholine esterase. Drugs, including some alkaloids, can interact with this process at several levels ... 

PB is used in the US Army as an antidote against the nerve gases sarin and soman (Fig. 4.25). PB is not a vaccine. As a 90-mg dose taken before a nerve gas attack, it increases the efficiency of other antidotes. The use of PB was approved by the FDA for this purpose in 2003 (12 years after the First Gulf War). Another medical use of PB used since 1955 is in treating a disease named myasthenia gravis, where the necessary daily dose is 1500 mg ( ). PB inhibits an enzyme called acetylchohne esterase, so it slows down the decay of the nenrotransmitter acetylcholine. Acetylcholine is a physiological antidote of adrenaline, and is formed at sites where there are parasympathetic nerve impulses. Acetylchohne dilates peripheral blood vessels, lowers blood pressure, slows down heartbeat and intensifies gastrointestinal motility. Its effect is short-lived as the enzyme acetylcholine esterase hydrolyzes it to chohne and acetic acid. 

Decamethonium bromide is used in surgery as a muscle relaxant. It acts by preventing the enzyme acetylcholine esterase from destroying acetylcholine (see page 327), a necessary step in the transmission of nerve impulses. Show how decamethonium bromide can be synthesized from a diamine and an alkyl halide. 

Enzymes Acetylcholin- esterase Catalysts of biochemical reactions (see Section 10.6.)... 

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