5.11
Cholinesterasen: Verteilung und Funktion
Cholinesterasen sind eine Gruppe von Serin-Hydrolase-Enzymen, die eine wichtige Rolle beim Abbau von Cholinsäureestern spielen. Die zwei Hauptarten vo…
Cholinesterasen sind Enzyme, die Cholinester spalten. Aufgrund ihrer Verteilung und Funktion existieren sie in zwei unterschiedlichen Typen: AChE oder echte Cholinesterasen und BuChE oder Pseudocholinesterasen.
Beide Typen haben globuläre katalytische Untereinheiten, die als lösliche Formen des Enzyms vorliegen können. Bei der gebundenen Form der Enzyme sind die katalytischen Komponenten über strukturelle Untereinheiten an der Membran verankert
.AChEs werden im rauen endoplasmatischen Retikulum synthetisiert und kommen hauptsächlich in cholinergen Neuronen und an den postsynaptischen Endplatten vor
Sie sind spezifisch für ACh und verwandte Ester. Die gebundenen AChEs an den cholinergen Synapsen hydrolysieren das freigesetzte ACh und beenden seine Wirkung.
Auf der anderen Seite werden BuChEs in der Leber synthetisiert. Gebundene BuChEs sind im Körper weit verbreitet, während die lösliche Form im Plasma zu finden ist.
BuChE hydrolysiert Butyrylcholin, ACh und andere esterhaltige Anästhetika. Es reguliert auch das Wachstum der Neuronen und die Zellproliferation.
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Q1: What are the two main types of cholinesterases and how do they differ?
Cholinesterases exist as two distinct types: acetylcholinesterases (AChEs), or true cholinesterases, and butyrylcholinesterases (BuChEs), or pseudocholinesterases. AChEs are specific for acetylcholine and related esters, while BuChEs are non-specific and hydrolyze butyrylcholine, acetylcholine, and ester-containing anesthetics. This substrate specificity difference reflects their distinct physiological roles in the body.
Q2: Where are acetylcholinesterases synthesized and located in the body?
Acetylcholinesterases are synthesized in the rough endoplasmic reticulum and are primarily found in cholinergic neurons and at postsynaptic end plates. The bound form anchors to neuronal membranes at cholinergic synapses, where it hydrolyzes released acetylcholine to terminate its action. Soluble forms are found in cerebrospinal fluid and help regulate free acetylcholine concentration.
Q3: What is the role of butyrylcholinesterase in drug metabolism?
Butyrylcholinesterase is synthesized in the liver and widely distributed throughout the body in bound form, while soluble forms circulate in plasma. The plasma form hydrolyzes acetylcholine and ester-containing anesthetic agents, leading to drug inactivation after administration. This makes BuChE crucial for metabolizing certain medications and regulating neurotransmitter levels.
Q4: How do soluble and bound forms of cholinesterases differ structurally?
Both cholinesterase types exist as soluble and bound forms. Soluble forms consist of a globular catalytic subunit found in cerebrospinal fluid or plasma. Bound forms link the catalytic unit to structural subunits that anchor the enzyme to membranes at neuronal synapses or neuromuscular junctions, enabling localized substrate hydrolysis.
Q5: What happens when acetylcholinesterase breaks down acetylcholine at the synapse?
Bound acetylcholinesterase at cholinergic synapses hydrolyzes released acetylcholine into choline and acetate, thereby terminating its neurotransmitter action. This enzymatic breakdown is essential for regulating cholinergic neurotransmission and preventing excessive acetylcholine accumulation. Understanding this mechanism is critical for studying indirect acting cholinergic agonists mechanism of action.
Q6: What additional functions does butyrylcholinesterase perform beyond acetylcholine hydrolysis?
Beyond hydrolyzing acetylcholine and ester-containing anesthetics, butyrylcholinesterase regulates neuronal outgrowth and cellular proliferation. This dual functionality makes BuChE important not only for neurotransmitter metabolism but also for developmental and cellular processes. Its widespread distribution in skin, brain, liver, and gut smooth muscles supports these diverse physiological roles.
Q7: Why is substrate specificity important for distinguishing acetylcholinesterase from butyrylcholinesterase?
Acetylcholinesterase shows high specificity for acetylcholine and related esters, making it ideal for precise synaptic regulation. Butyrylcholinesterase is non-specific and hydrolyzes multiple ester-containing compounds, including anesthetics. This specificity difference determines their distinct tissue distributions and clinical significance in drug metabolism and neurotransmission.