2 by: Kristina Dodd

Student – Kristina Dodd

Name of Enzyme: Acetylcholinesterase

EC Number: 3.1.1.7

Where is acetylcholinesterase found? Acetylcholinesterase is found in the neuromuscular junction between a somatic motor neuron and a skeletal muscle fiber. Neuromuscular junctions can be found throughout nervous tissue in the body involved in the central nervous system as well as the peripheral nervous system. Within the neuromuscular junction, acetylcholinesterase is located specifically on the end plate membrane of the post-synaptic skeletal muscle cell.

What does acetylcholinesterase do? The purpose of acetylcholinesterase within the neuromuscular junction is to rapidly hydrolyse the neurotransmitter acetylcholine in the synaptic cleft into choline and acetic acid. Once acetylcholine diffuses across the synaptic cleft, it binds to the acetylcholine receptors where Na+ channels are opened, and depolarization of the postsynaptic membrane leads to the formation of graded potentials. These graded potentials if strong enough will lead to action potentials, causing the muscle cell to contract. Once the action potential on the presynaptic somatic motor neuron ceases, no more acetylcholine is released into the synaptic cleft, however the acetylcholine already present in the synaptic cleft will remain there and continue to depolarize the postsynaptic muscle cell. The purpose of the enzyme acetylcholinesterase is to break down the remaining acetylcholine in the synaptic cleft by cleaving it into choline and acetic acid, which will prevent the opening of the cation channel on the motor end plate, and the muscle action potential will no longer be able to initiate. The inhibition of the formation of a muscle action potential ceases the muscle from contracting, allowing it to relax and return to a rest state.

Interesting facts about acetylcholinesterase – Acetylcholinesterase is a very important enzyme in the neuromuscular junction. If there was no acetylcholinesterase present on the end-plate membrane, the muscle would start to uncontrollably contract, eventually leading to paralysis as the muscle cells become resistant to any stimulation or action potentials sent to the muscle cells. Acetylcholinesterase inhibitors are used as drugs and toxins depending on if they are reversible or irreversible inhibitors. Reversible acetylcholinesterase inhibitors can be used as a treatment for neurodegenerative disorders including Alzheimer’s disease due to one of the results of the disease being a decrease in acetylcholine present. Irreversible acetylcholinesterase inhibitors can be classified as a group of organic compounds called Organophosphates which are used as insecticides in agriculture and in households, nerve agents and chemical weapons and therapeutic agents. Acetylcholinesterase is an essential enzyme in the body in order for muscle cells throughout the body to function properly.

References

Colović, M. B., Krstić, D. Z., Lazarević-Pašti, T. D., Bondžić, A. M., & Vasić, V. M. (2013).   Acetylcholinesterase inhibitors: pharmacology and toxicology. Current Neuropharmacology, 11(3), 315-335. https://doi.org/10.2174/1570159×11311030006

Derrickson, B. H. (2024). Human physiology (3rd ed.). John Wiley & Sons.

Fields, M. J.,& Wymore, T. W. (2014). Multiscale modeling of a nerve agent hydrolysis mechanism: a tale of two Nobel Prizes. Physica Scripta, 89(10). https://doi.org/10.1088/0031-8949/89/10/108004

National Center for Biotechnology Information. (2024) Acetylcholinesterase (EC 3.1.1.7). PubChem. https://pubchem.ncbi.nlm.nih.gov/protein/EC:3.1.1.7

National Center for Biotechnology Information. (2024) Acetylcholinesterase (human). PubChem. https://pubchem.ncbi.nlm.nih.gov/protein/P22303

Nelson, D. L., & Cox, M. M. (2017). Principles of Biochemistry (7th ed.). Lehninger.

Trang, A., & Khandhar, P. B. (2023). Physiology, acetylcholinesterase. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK539735/