3 by: Megan Hills
Student: Megan Hills
Enzyme: Acetylcholinesterase
E.C Number: 3.1.1.7
Acetylcholinesterase is a monomer enzyme that breaks the substrate Acetylcholine down in the postsynaptic neuromuscular junctions that are in muscles and nerves. It is distributed in the brainstem, cerebellum and peripheral and autonomic nervous system tissues. Acetylcholinesterase is also found in skeletal muscle and present in red blood cell membranes. The enzyme breaks acetylcholine down into acetic acid and choline. Its primary function is to stop neural transmission, but findings suggest that Acetylcholinesterase is also important in fetal development. In fetal development, it assists morphogenesis which is the embryological shaping of an organism.
Acetylcholinesterase is a serine hydrolase that creates a tetrahedral intermediate. It does so through acid-base reactions with a catalytic triad of serine, histidine and acid residue. Histidine’s role is to transfer a proton between the oxygen molecules in serine and acetylcholine. This removes choline from acetylcholine to form a new acylated serine. The acylated serine then gets deacylated and the regeneration of acetylcholinesterase starts. Aspartate stabilizes the protonated histidine, therefore releasing acetic acid and a new free enzyme. Tyrosine, phenylalanine, tryptophan makes up the peripheral anionic site and influence the binding of acetylcholine to the site.
Acetylcholinesterase inhibitors can be either reversible or irreversible. Organophosphates and carbamates are two different kinds of acetylcholinesterase inhibitors. Organophosphates are more toxic and have a longer duration of action than carbamates. They are reversible inhibitors. Exposure to organophosphates may cause symptoms like confusion, headaches, impaired memory and neurotoxic effects. Although they are toxic, they are prescribed to Alzheimer’s patients for therapeutic relief. Alzheimer’s patients have a loss of cholinergic neurons which causes the symptoms of declining and slowing short-term memory, but the inhibitors raise the concentration of acetylcholine. The remaining Acetylcholine recalibrates the neurotransmitter to sufficient levels which declines the progression of the disease. There are side effects that can be negative to the patient such as an imbalance of acetylcholinesterase which could worsen the physical state of the Alzheimer’s patient.
The Acetylcholinesterase inhibitor attaches to the serine hydroxyl group in the esteratic site of the acetylcholinesterase which prevents the interaction between acetylcholinesterase and acetylcholine, therefore preventing the breakdown of acetylcholine. The phosphorus on the acetylcholinesterase inhibitor is partially electropositive and the oxygen on the serine group is partially electronegative which causes an attraction between the two. The Histidine Nitrogen binds to the Hydrogen on the Serine group. This inhibits the binding of the acetyl group of acetylcholine to the esteratic site on the acetylcholinesterase. Since the acetyl group can’t bind to the acetylcholinesterase, the acetylcholine can’t be split so it will accumulate in the synapses.
References:
Britannica, T. Editors of Encyclopaedia (2021, December 15). morphogenesis. Encyclopedia Britannica. Retrieved from Morphogenesis | Definition, Types, & Facts | Britannica
Trang, A., Khandhar, P.B. (January 19, 2023). Physiology, Acetylcholinesterase. 8600 Rockville Pike, Bethesda, MD: National Library of Medicine. Retrieved from Physiology, Acetylcholinesterase – StatPearls – NCBI Bookshelf (nih.gov)
n.a, (June 26, 2023). Cholinesterase Inhibitors: Including Insecticides and Chemical Warfare Nerve Agents. Agency for Toxic Substances and Disease Registry. Retrieved from Cholinesterase Inhibitors: Part 2: What are cholinesterase inhibitors? | Environmental Medicine | ATSDR (cdc.gov)
n.a, (August 21, 2024). Acetylcholinesterase Inhibitor. Wikipedia. Retrieved from Acetylcholinesterase inhibitor – Wikipedia
n.a, (n.d). Expasy: Acetylcholinesterase. SIB Swiss Institute of Bioinformatics. Retrieved from ENZYME – 3.1.1.7 acetylcholinesterase (expasy.org)
