5.11:
Cholinesterases: Distribution and Function
Cholinesterases are enzymes that cleave choline esters. Based on their distribution and function, they exist as two distinct types: AChEs, or true cholinesterases and BuChEs, or pseudocholinesterases.
Both types have globular catalytic subunits, which can exist as the soluble forms of the enzyme. The bound form of the enzymes has the catalytic components anchored to the membrane via structural subunits.
AChEs are synthesized in the rough endoplasmic reticulum and are primarily found in cholinergic neurons and at the postsynaptic end plates
They are specific for ACh and related esters. The bound AChEs at the cholinergic synapses hydrolyze the released ACh, terminating its action.
On the other hand, BuChEs are synthesized in the liver. Bound BuChEs are widely distributed in the body, while the soluble form is found in the plasma.
BuChE hydrolyzes butyrylcholine, ACh and other ester-containing anesthetics. It also regulates outgrowth of the neurons and cellular proliferation.
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.