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5.11 : Cholinesterases: Distribution and Function

Cholinesterases are a group of serine hydrolase enzymes that play a crucial role in the breakdown of choline esters. The two primary types of cholinesterases are acetylcholinesterases (AChEs) and butyrylcholinesterase (BuChEs), which differ in their distribution, function, and substrate specificity. AChEs, also known as true cholinesterases, specifically hydrolyze acetylcholine, while BuChEs, often referred to as pseudocholinesterases, can hydrolyze various choline esters, including butyrylcholine, making them non-specific.

These enzymes exist in both soluble and bound forms. Soluble forms, which consist of a globular catalytic subunit, are found in cerebrospinal fluid (AChE) and plasma (BuChE). The bound form links the catalytic unit to accessory proteins, anchoring the enzyme either to neuronal membranes at the neuronal synapse, or to basement membranes at the neuromuscular junction.

AChEs are primarily synthesized in the rough endoplasmic reticulum and are predominantly located in neuromuscular junctions, cholinergic neuron terminals, and red blood cells. Bound AChE at cholinergic neuron synapses hydrolyzes released acetylcholine into choline and acetate, thereby terminating its actions. Soluble AChE helps regulate concentration of free acetylcholine. Additionally, AChE can also hydrolyze neuropeptides such as substance P, although the physiological significance remains unclear.

In contrast to AChE, BuChE is mainly synthesized in the liver, and its bound form is widely distributed across the skin, brain, liver, and smooth muscles of the gut. The bound form of BuChE present in plasma is responsible for the hydrolysis of acetylcholine and ester-containing agents, such as anesthetics, leading to the inactivation of these drugs after administration.

Tags

CholinesterasesSerine HydrolaseAcetylcholinesterase AChEButyrylcholinesterase BuChESubstrate SpecificitySoluble FormsBound FormsNeuromuscular JunctionCholinergic NeuronsAcetylcholine HydrolysisEnzyme DistributionPhysiological SignificanceNeuropeptidesDrug Inactivation

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