Acetylcholinesterase and Butyrylcholinesterase Substrate Selectivity and Various Acting Cholinesterase Inhibitors
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 transmission at cholinergic synapses through hydrolysis of ACh (Rang & Dale, 2007). Produced in the liver, BChE resides in the plasma and many tissues.
Similarly, both enzymes hydrolyse ACh to choline and acetic acid with BChE hydrolysing BCh more rapidly than ACh (Rang & Dale., 2007). The substrate traffic in AChE involves two distinct binding sites, the catalytic and peripheral anionic sites, with BChE having relatively broader substrate specificity than AChE (Colletier et al., 2006).
Anticholinesterases (AnAChE’s) inhibit cholinesterase activity and depending upon the nature of their interaction with the active site are categorised as either short/medium duration or irreversible (Rang & Dale, 2007).
The study of cholinesterase hydrolysis and inhibitory actions demonstrate the key pharmacological principles of enzymatic catalysis and proteins as targets for drug action. Their importance is evident in a study conducted by Kumar et al (1989), where significantly lower cerebrospinal fluid AChE activity in early onset patients of Alzheimer’s disease and an altered AChE/BChE ratio, lead to elevated levels of choline.
The present study has two primary aims. The first is to demonstrate the substrate selectivity of AChE and BChE
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 transmission at cholinergic synapses through hydrolysis of ACh (Rang & Dale, 2007). Produced in the liver, BChE resides in the plasma and many tissues.
Similarly, both enzymes hydrolyse ACh to choline and acetic acid with BChE hydrolysing BCh more rapidly than ACh (Rang & Dale., 2007). The substrate traffic in AChE involves two distinct binding sites, the catalytic and peripheral anionic sites, with BChE having relatively broader substrate specificity than AChE (Colletier et al., 2006).
Anticholinesterases (AnAChE’s) inhibit cholinesterase activity and depending upon the nature of their interaction with the active site are categorised as either short/medium duration or irreversible (Rang & Dale, 2007).
The study of cholinesterase hydrolysis and inhibitory actions demonstrate the key pharmacological principles of enzymatic catalysis and proteins as targets for drug action. Their importance is evident in a study conducted by Kumar et al (1989), where significantly lower cerebrospinal fluid AChE activity in early onset patients of Alzheimer’s disease and an altered AChE/BChE ratio, lead to elevated levels of choline.
The present study has two primary aims. The first is to demonstrate the substrate selectivity of AChE and BChE
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