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Acetylcholinesterase and Butyrylcholinesterase Substrate Selectivity and Various Acting Cholinesterase Inhibitors

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Acetylcholinesterase and Butyrylcholinesterase substrate selectivity and various acting cholinesterase inhibitors
Introduction
Cholinesterases are a group of enzymes present in mammals which breakdown certain neurotransmitters by hydrolyzing the ester bonds within a molecule (Rang & Dale, 2007). There are two major types of enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Though similar in structure, they differ in distribution, function and substrate specificity.
AChE is found in red blood cells, cholinergic fibres and muscle (motor end-plate), existing as mainly membrane bound (Rang & Dale, 2007). It is highly specific for the neurotransmitter acetylcholine (ACh) and its principle role is termination of impulse
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Discussion:
It was found that BChE showed broader substrate specificity when compared to AChE, hydrolysing all substrates (at least to some extent), excluding Carbachol. AChE failed to hydrolyse suxamethonium or carbachol to any extent. It was also found that Atropine and Malathion failed to significantly inhibit either cholinesterase, whereas Edrophonium displayed short-acting inhibition. Physostigmine, Nestogmine and Carbachol displayed greater inhibition.
(1) AChE and BChE showed greatest activity when hydrolysing their native substrates; ACh and BCh respectively. AChE rapidly hydrolysed ACh, however it hydrolysed BCh at a minimal rate (0.83%). In contrast, BChE showed comparatively minimal difference in catalytic efficiency in the hydrolysis of ACh, upon which is concurrent with Radic et al (1993) (Figure1).
Owing to its large acyl pocket, BChE is capable of accommodating larger substrates such as the four-carbon acyl-group of the BCh, making hydrolysis of BCh or the smaller ACh catalytically efficient (Radic et al., 1993). Furthermore, this principle explains why BChE was capable of effectively hydrolysing benzoylcholine which contains a large acyl group in the form of an aromatic ring (Figure1). When compared to AChE, whose acyl pocket is much smaller; BCh, suxamethonium (which contains a large acyl-quaternary nitrogen) and benzoylcholine are unable to effectively fit
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