Acetylcholinesterase

Last updated

acetylcholinesterase
The reaction catalyzed by acetylcholinesterase.tif
Acetylcholinesterase catalyzes the hydrolysis of acetylcholine to acetate ion and choline
Identifiers
EC no. 3.1.1.7
CAS no. 9000-81-1
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
Search
PMC articles
PubMed articles
NCBI proteins
ACHE
PBB Protein ACHE image.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases ACHE , AChE, acetylhydrolase, acetylcholinesterase (Yt blood group), ACEE, ARN-YT, acetylcholinesterase (Cartwright blood group), true cholinesterase (dated synonym)
External IDs OMIM: 100740; MGI: 87876; HomoloGene: 543; GeneCards: ACHE; OMA:ACHE - orthologs
Orthologs
SpeciesHumanMouse
Entrez

43

11423

Ensembl

ENSG00000087085

ENSMUSG00000023328

UniProt

P22303

P21836

RefSeq (mRNA)

NM_001290010
NM_009599

RefSeq (protein)

NP_001276939
NP_033729

Location (UCSC) Chr 7: 100.89 – 100.9 Mb Chr 5: 137.29 – 137.29 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acetylcholine and some other choline esters that function as neurotransmitters:

acetylcholine + H2O = choline + acetate

It is found at mainly neuromuscular junctions and in chemical synapses of the cholinergic type, where its activity serves to terminate cholinergic synaptic transmission. It belongs to the carboxylesterase family of enzymes. It is the primary target of inhibition by organophosphorus compounds such as nerve agents and pesticides.

Enzyme structure and mechanism

AChe mechanism of action AChe mechanism of action.jpg
AChe mechanism of action

AChE is a hydrolase that hydrolyzes choline esters. It has a very high catalytic activity—each molecule of AChE degrades about 5,000 molecules of acetylcholine (ACh) per second, [6] approaching the limit allowed by diffusion of the substrate. [7] [8] The active site of AChE comprises two subsites—the anionic site and the esteratic subsite. The structure and mechanism of action of AChE have been elucidated from the crystal structure of the enzyme. [9] [10]

The anionic subsite accommodates the positive quaternary amine of acetylcholine as well as other cationic substrates and inhibitors. The cationic substrates are not bound by a negatively charged amino acid in the anionic site, but by interaction of 14 aromatic residues that line a gorge leading to the active site. [11] [12] [13] All 14 amino acids in the aromatic gorge are highly conserved across different species. [14] Among the aromatic amino acids, tryptophan 84 is critical and its substitution with alanine results in a 3000-fold decrease in reactivity. [15] The gorge is approximately 20 angstroms deep and five angstroms wide. [16]

The esteratic subsite, where acetylcholine is hydrolyzed to acetate and choline, contains the catalytic triad of three amino acids: serine 203, histidine 447 and glutamate 334. These three amino acids are similar to the triad in other serine proteases except that the glutamate is the third member rather than aspartate. Moreover, the triad is of opposite chirality to that of other proteases. [17] The hydrolysis reaction of the carboxyl ester leads to the formation of an acyl-enzyme and free choline. Then, the acyl-enzyme undergoes nucleophilic attack by a water molecule, assisted by the histidine 440 group, liberating acetic acid and regenerating the free enzyme. [18] [19]

Species

AChE is found in many biological species, including humans and other mammals, non-vertebrates, and plants. [20] [21] [22] [23]

In humans, AChE is a cholinergic enzyme involved in the hydrolysis of the neurotransmitter acetylcholine (ACh) into its constituents, choline, and acetate. [20] Overall, in mammals, AChE is primarily involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter acetylcholine. [20] In non-vertebrates, AChE plays a similar role in nerve conduction processes at the neuromuscular junction. It is usually located in the membranes of these animals and controls ionic currents in excitable membranes. [22] [23]

In plants, the biological functions of AChE are less clear, and its existence has been recognized by indirect evidence of its activity. For instance, a study on Solanum lycopersicum (tomato) identified 87 SlAChE genes containing GDSL lipase/acylhydrolase domain. The study also showed up-and down-regulation of SlAChE genes under salinity stress condition. [20]

Some marine fungi have been found to produce compounds that inhibit AChE. However, the specific role and mechanisms of AChE in fungi are not as well-studied as in mammals. [23] The presence and role of AChE in bacteria is not well-documented. [23]

Biological function

During neurotransmission, ACh is released from the presynaptic neuron into the synaptic cleft and binds to ACh receptors on the post-synaptic membrane, relaying the signal from the nerve. AChE is concentrated in the synaptic cleft, where it terminates the signal transmission by hydrolyzing ACh. [6] The liberated choline is taken up again by the pre-synaptic neuron and ACh is synthesized by combining with acetyl-CoA through the action of choline acetyltransferase. [24] [25]

A cholinomimetic drug disrupts this process by acting as a cholinergic neurotransmitter that is impervious to acetylcholinesterase's lysing action.[ citation needed ]

Disease relevance

Drugs or toxins that inhibit AChE lead to persistence of high concentrations of ACh within synapses, leading to increased cholinergic signaling within the central nervous system, autonomic ganglia and neuromuscular junctions. [26]

Mechanism of Inhibitors of AChE AChe inhibitors pic.jpg
Mechanism of Inhibitors of AChE

Irreversible inhibitors of AChE may lead to muscular paralysis, convulsions, bronchial constriction, and death by asphyxiation. Organophosphates (OP), esters of phosphoric acid, are a class of irreversible AChE inhibitors. [27] Cleavage of OP by AChE leaves a phosphoryl group in the esteratic site, which is slow to be hydrolyzed (on the order of days) and can become covalently bound. Irreversible AChE inhibitors have been used in insecticides (e.g., malathion) and nerve gases for chemical warfare (e.g., Sarin and VX). Carbamates, esters of N-methyl carbamic acid, are AChE inhibitors that hydrolyze in hours and have been used for medical purposes (e.g., physostigmine for the treatment of glaucoma). Reversible inhibitors occupy the esteratic site for short periods of time (seconds to minutes) and are used to treat of a range of central nervous system diseases. Tetrahydroaminoacridine (THA) and donepezil are FDA-approved to improve cognitive function in Alzheimer's disease. Rivastigmine is also used to treat Alzheimer's and Lewy body dementia, and pyridostigmine bromide is used to treat myasthenia gravis. [28] [29] [30] [31] [32] [33]

An endogenous inhibitor of AChE in neurons is Mir-132 microRNA, which may limit inflammation in the brain by silencing the expression of this protein and allowing ACh to act in an anti-inflammatory capacity. [34]

It has also been shown that the main active ingredient in cannabis, tetrahydrocannabinol, is a competitive inhibitor of acetylcholinesterase. [35]

Distribution

AChE is found in many types of conducting tissue: nerve and muscle, central and peripheral tissues, motor and sensory fibers, and cholinergic and noncholinergic fibers. The activity of AChE is higher in motor neurons than in sensory neurons. [36] [37] [38]

Acetylcholinesterase is also found on the red blood cell membranes, where different forms constitute the Yt blood group antigens. [39] Acetylcholinesterase exists in multiple molecular forms, which possess similar catalytic properties, but differ in their oligomeric assembly and mode of attachment to the cell surface.[ citation needed ]

AChE gene

In mammals, acetylcholinesterase is encoded by a single AChE gene while some invertebrates have multiple acetylcholinesterase genes. Note higher vertebrates also encode a closely related paralog BCHE (butyrylcholinesterase) with 50% amino acid identity to ACHE. [40] Diversity in the transcribed products from the sole mammalian gene arises from alternative mRNA splicing and post-translational associations of catalytic and structural subunits. There are three known forms: T (tail), R (read through), and H (hydrophobic). [41]

AChET

The major form of acetylcholinesterase found in brain, muscle, and other tissues, known as is the hydrophilic species, which forms disulfide-linked oligomers with collagenous, or lipid-containing structural subunits. In the neuromuscular junctions AChE expresses in asymmetric form which associates with ColQ or subunit. In the central nervous system it is associated with PRiMA which stands for Proline Rich Membrane anchor to form symmetric form. In either case, the ColQ or PRiMA anchor serves to maintain the enzyme in the intercellular junction, ColQ for the neuromuscular junction and PRiMA for synapses.

AChEH

The other, alternatively spliced form expressed primarily in the erythroid tissues, differs at the C-terminus, and contains a cleavable hydrophobic peptide with a PI-anchor site. It associates with membranes through the phosphoinositide (PI) moieties added post-translationally. [42]

AChER

The third type has, so far, only been found in Torpedo sp. and mice although it is hypothesized in other species. It is thought to be involved in the stress response and, possibly, inflammation. [43]

Nomenclature

The nomenclatural variations of ACHE and of cholinesterases generally are discussed at Cholinesterase § Types and nomenclature .

Inhibitors

For acetylcholine esterase (AChE), reversible inhibitors are those that do not irreversibly bond to and deactivate AChE. [44] Drugs that reversibly inhibit acetylcholine esterase are being explored as treatments for Alzheimer's disease and myasthenia gravis, among others. Examples include tacrine and donepezil. [45]

Exposure to acetylcholinesterase inhibitors is one of several studied explanations for the chronic cognitive symptoms veterans displayed after returning from the Gulf War. Soldiers were dosed with AChEI pyridostigmine bromide (PB) as protection from nerve agent weapons. Studying acetylcholine levels using microdialysis and HPLC-ECD, researchers at the University of South Carolina School of Medicine determined PB, when combined with a stress element can lead to cognitive responses. [46]

See also

Related Research Articles

<span class="mw-page-title-main">Acetylcholine</span> Organic chemical and neurotransmitter

Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic.

<span class="mw-page-title-main">Soman</span> Chemical compound (nerve agent)

Soman is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibiting the enzyme cholinesterase. It is an inhibitor of both acetylcholinesterase and butyrylcholinesterase. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations according to UN Resolution 687. Its production is strictly controlled, and stockpiling is outlawed by the Chemical Weapons Convention of 1993 where it is classified as a Schedule 1 substance. Soman was the third of the so-called G-series nerve agents to be discovered along with GA (tabun), GB (sarin), and GF (cyclosarin).

<span class="mw-page-title-main">Cholinesterase</span> Esterase that lyses choline-based esters

The enzyme cholinesterase (EC 3.1.1.8, choline esterase; systematic name acylcholine acylhydrolase) catalyses the hydrolysis of choline-based esters:

<span class="mw-page-title-main">Choline acetyltransferase</span> Protein-coding gene in the species Homo sapiens

Choline acetyltransferase is a transferase enzyme responsible for the synthesis of the neurotransmitter acetylcholine. ChAT catalyzes the transfer of an acetyl group from the coenzyme acetyl-CoA to choline, yielding acetylcholine (ACh). ChAT is found in high concentration in cholinergic neurons, both in the central nervous system (CNS) and peripheral nervous system (PNS). As with most nerve terminal proteins, ChAT is produced in the body of the neuron and is transported to the nerve terminal, where its concentration is highest. Presence of ChAT in a nerve cell classifies this cell as a "cholinergic" neuron. In humans, the choline acetyltransferase enzyme is encoded by the CHAT gene.

A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs because acetylcholine (ACh) is the neurotransmitter used by the PSNS. Chemicals in this family can act either directly by stimulating the nicotinic or muscarinic receptors, or indirectly by inhibiting cholinesterase, promoting acetylcholine release, or other mechanisms. Common uses of parasympathomimetics include glaucoma, Sjögren syndrome and underactive bladder.

<span class="mw-page-title-main">Nicotinic acetylcholine receptor</span> Acetylcholine receptors named for their selective binding of nicotine

Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral nervous system, muscle, and many other tissues of many organisms. At the neuromuscular junction they are the primary receptor in muscle for motor nerve-muscle communication that controls muscle contraction. In the peripheral nervous system: (1) they transmit outgoing signals from the presynaptic to the postsynaptic cells within the sympathetic and parasympathetic nervous system, and (2) they are the receptors found on skeletal muscle that receive acetylcholine released to signal for muscular contraction. In the immune system, nAChRs regulate inflammatory processes and signal through distinct intracellular pathways. In insects, the cholinergic system is limited to the central nervous system.

<span class="mw-page-title-main">Galantamine</span> Neurological medication

Galantamine is a type of acetylcholinesterase inhibitor. It is an alkaloid extracted from the bulbs and flowers of Galanthus nivalis, Galanthus caucasicus, Galanthus woronowii, and other members of the family Amaryllidaceae, such as Narcissus (daffodil), Leucojum aestivum (snowflake), and Lycoris including Lycoris radiata. It can also be produced synthetically.

Pseudocholinesterase deficiency is an autosomal recessive inherited blood plasma enzyme abnormality in which the body's production of butyrylcholinesterase is impaired. People who have this abnormality may be sensitive to certain anesthetic drugs, including the muscle relaxants succinylcholine and mivacurium as well as other ester local anesthetics.

<span class="mw-page-title-main">Huperzine A</span> Chemical compound

Huperzine A is a naturally-occurring sesquiterpene alkaloid compound found in the firmoss Huperzia serrata and in varying quantities in other food Huperzia species, including H. elmeri, H. carinat, and H. aqualupian. Huperzine A has been investigated as a treatment for neurological conditions such as Alzheimer's disease, but a 2013 meta-analysis of those studies concluded that they were of poor methodological quality and the findings should be interpreted with caution. Huperzine A inhibits the breakdown of the neurotransmitter acetylcholine (ACh) by the enzyme acetylcholinesterase. It is also an antagonist of the NMDA-receptor. It is commonly available over the counter as a nutritional supplement and marketed as a memory and concentration enhancer.

<span class="mw-page-title-main">Diisopropyl fluorophosphate</span> Chemical compound

Diisopropyl fluorophosphate (DFP) or Isoflurophate is an oily, colorless liquid with the chemical formula C6H14FO3P. It is used in medicine and as an organophosphorus insecticide. It is stable, but undergoes hydrolysis when subjected to moisture.

<span class="mw-page-title-main">Azinphos-methyl</span> Chemical compound

Azinphos-methyl (Guthion) is a broad spectrum organophosphate insecticide manufactured by Bayer CropScience, Gowan Co., and Makhteshim Agan. Like other pesticides in this class, it owes its insecticidal properties to the fact that it is an acetylcholinesterase inhibitor. It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act, and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.

Neurotransmitter transporters are a class of membrane transport proteins that span the cellular membranes of neurons. Their primary function is to carry neurotransmitters across these membranes and to direct their further transport to specific intracellular locations. There are more than twenty types of neurotransmitter transporters.

<span class="mw-page-title-main">Butyrylcholinesterase</span> Mammalian protein found in humans

Butyrylcholinesterase, also known asBChE, BuChE, BuChase, pseudocholinesterase, or plasma (cholin)esterase, is a nonspecific cholinesterase enzyme that hydrolyses many different choline-based esters. In humans, it is made in the liver, found mainly in blood plasma, and encoded by the BCHE gene.

Ambenonium is a cholinesterase inhibitor used in the management of myasthenia gravis.

<span class="mw-page-title-main">Acetylcholinesterase inhibitor</span> Drugs that inhibit acetylcholinesterase

Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and duration of action of acetylcholine in the central nervous system, autonomic ganglia and neuromuscular junctions, which are rich in acetylcholine receptors. Acetylcholinesterase inhibitors are one of two types of cholinesterase inhibitors; the other being butyryl-cholinesterase inhibitors. Acetylcholinesterase is the primary member of the cholinesterase enzyme family.

<span class="mw-page-title-main">Cholinesterase inhibitor</span> Chemicals which prevent breakdown of acetylcholine and butyrylcholine

Cholinesterase inhibitors (ChEIs), also known as anti-cholinesterase, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine by cholinesterase. This increases the amount of the acetylcholine or butyrylcholine in the synaptic cleft that can bind to muscarinic receptors, nicotinic receptors and others. This group of inhibitors is divided into two subgroups, acetylcholinesterase inhibitors (AChEIs) and butyrylcholinesterase inhibitors (BChEIs).

<span class="mw-page-title-main">Choline transporter</span> Protein-coding gene in the species Homo sapiens

The high-affinity choline transporter (ChT) also known as solute carrier family 5 member 7 is a protein in humans that is encoded by the SLC5A7 gene. It is a cell membrane transporter and carries choline into acetylcholine-synthesizing neurons.

<span class="mw-page-title-main">Rivastigmine</span> Chemical compound

Rivastigmine, sold under the brand name Exelon among others, is an acetylcholinesterase inhibitor used for the treatment of dementia associated with Alzheimer's disease and with Parkinson's disease. Rivastigmine can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which typically include nausea and vomiting.

<span class="mw-page-title-main">Cymserine</span> Chemical compound

Cymserine is a drug related to physostigmine, which acts as a reversible cholinesterase inhibitor, with moderate selectivity (15×) for the plasma cholinesterase enzyme butyrylcholinesterase, and relatively weaker inhibition of the better-known acetylcholinesterase enzyme. This gives it a much more specific profile of effects that may be useful for treating Alzheimer's disease without producing side effects such as tremors, lacrimation, and salivation that are seen with the older nonselective cholinesterase inhibitors currently used for this application, such as donepezil. A number of cymserine derivatives have been developed with much greater selectivity for butyrylcholinesterase, and both cymserine and several of its analogues have been tested in animals, and found to increase brain acetylcholine levels and produce nootropic effects, as well as reducing levels of amyloid precursor protein and amyloid beta, which are commonly used biomarkers for the development of Alzheimer's disease.

<span class="mw-page-title-main">Hermona Soreq</span> Israeli biologist

Hermona Soreq is an Israeli professor of Molecular Neuroscience at The Hebrew University of Jerusalem. Best known for her work on the signaling of acetylcholine and its relevance in stress responses and neurodegenerative diseases such as Parkinson's and Alzheimer's.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000087085 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000023328 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Katzung BG (2001). "Introduction to Autonomic Pharmacology". Basic and Clinical Pharmacology (8th ed.). McGraw-Hill. pp. 75–91. ISBN   978-0-07-160405-5.
  6. 1 2 Purves D, Augustine GJ, Fitzpatrick D, Katz LC, LaMantia AS, McNamara JO, et al. (2001). "Chapter 6. Neurotransmitters: Acetylcholine". Neuroscience (2nd ed.). Sunderland (MA): Sinauer Associates. ISBN   978-0-87893-697-7.
  7. ↑ Quinn DM (1987). "Acetylcholinesterase: enzyme structure, reaction dynamics, and virtual transition states". Chemical Reviews. 87 (5): 955–79. doi:10.1021/cr00081a005.
  8. ↑ Taylor P, Radić Z (1994). "The cholinesterases: from genes to proteins". Annual Review of Pharmacology and Toxicology. 34: 281–320. doi:10.1146/annurev.pa.34.040194.001433. PMID   8042853.
  9. ↑ Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, et al. (August 1991). "Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein". Science. 253 (5022): 872–9. Bibcode:1991Sci...253..872S. doi:10.1126/science.1678899. PMID   1678899. S2CID   28833513.
  10. ↑ Sussman JL, Harel M, Silman I (June 1993). "Three-dimensional structure of acetylcholinesterase and of its complexes with anticholinesterase drugs". Chem. Biol. Interact. 87 (1–3): 187–97. Bibcode:1993CBI....87..187S. doi:10.1016/0009-2797(93)90042-W. PMID   8343975.
  11. ↑ Radić Z, Gibney G, Kawamoto S, MacPhee-Quigley K, Bongiorno C, Taylor P (October 1992). "Expression of recombinant acetylcholinesterase in a baculovirus system: kinetic properties of glutamate 199 mutants". Biochemistry. 31 (40): 9760–7. doi:10.1021/bi00155a032. PMID   1356436.
  12. ↑ Ordentlich A, Barak D, Kronman C, Ariel N, Segall Y, Velan B, et al. (February 1995). "Contribution of aromatic moieties of tyrosine 133 and of the anionic subsite tryptophan 86 to catalytic efficiency and allosteric modulation of acetylcholinesterase". J. Biol. Chem. 270 (5): 2082–91. doi: 10.1074/jbc.270.5.2082 . PMID   7836436.
  13. ↑ Ariel N, Ordentlich A, Barak D, Bino T, Velan B, Shafferman A (October 1998). "The 'aromatic patch' of three proximal residues in the human acetylcholinesterase active centre allows for versatile interaction modes with inhibitors". Biochem. J. 335 (1): 95–102. doi:10.1042/bj3350095. PMC   1219756 . PMID   9742217. Open Access logo PLoS transparent.svg
  14. ↑ Ordentlich A, Barak D, Kronman C, Flashner Y, Leitner M, Segall Y, et al. (August 1993). "Dissection of the human acetylcholinesterase active center determinants of substrate specificity. Identification of residues constituting the anionic site, the hydrophobic site, and the acyl pocket". J. Biol. Chem. 268 (23): 17083–95. doi: 10.1016/S0021-9258(19)85305-X . PMID   8349597. Open Access logo PLoS transparent.svg
  15. ↑ Tougu V (2001). "Acetylcholinesterase: Mechanism of Catalysis and Inhibition". Current Medicinal Chemistry - Central Nervous System Agents. 1 (2): 155–170. doi:10.2174/1568015013358536. Closed Access logo transparent.svg
  16. ↑ Cheng S, Song W, Yuan X, Xu Y (2017). "Gorge Motions of Acetylcholinesterase Revealed by Microsecond Molecular Dynamics Simulations". Scientific Reports. 7 (1): 3219. Bibcode:2017NatSR...7.3219C. doi: 10.1038/s41598-017-03088-y . PMC   5468367 . PMID   28607438.
  17. ↑ Tripathi A (October 2008). "Acetylcholinsterase: A Versatile Enzyme of Nervous System". Annals of Neurosciences. 15 (4): 106–111. doi:10.5214/ans.0972.7531.2008.150403.
  18. ↑ Pauling L (1946). "Molecular Architecture and Biological Reactions" (PDF). Chemical & Engineering News. 24 (10): 1375–1377. doi:10.1021/cen-v024n010.p1375.
  19. ↑ Fersht A (1985). Enzyme structure and mechanism. San Francisco: W.H. Freeman. p. 14. ISBN   0-7167-1614-3.
  20. 1 2 3 4 Sarangle Y, Bamel K, Purty RS (2023). "Identification of Acetylcholinesterase Like Gene Family and Its Expression Under Salinity Stress in Solanum lycopersicum". Journal of Plant Growth Regulation. 43 (3): 940–960. doi:10.1007/s00344-023-11152-3. S2CID   265016505.
  21. ↑ Tripathi A, Srivastava UC (January 2, 2010). "Acetylcholinesterase :A Versatile Enzyme of Nervous System". Annals of Neurosciences. 15 (4): 106–111. doi:10.5214/ans.0972.7531.2008.150403.
  22. 1 2 Gaitonde D, Sarkar A, Kaisary S, Silva CD, Dias C, Rao DP, et al. (2006). "Acetylcholinesterase activities in marine snail (Cronia contracta) as a biomarker of neurotoxic contaminants along the Goa coast, West coast of India". Ecotoxicology. 15 (4): 353–358. Bibcode:2006Ecotx..15..353G. doi:10.1007/s10646-006-0075-3. PMID   16676216. S2CID   25702252.
  23. 1 2 3 4 Nie Y, Yang W, Liu Y, Yang J, Lei X, Gerwick WH, et al. (2020). "Acetylcholinesterase inhibitors and antioxidants mining from marine fungi: Bioassays, bioactivity coupled LC–MS/MS analyses and molecular networking". Marine Life Science & Technology. 2 (4): 386–397. Bibcode:2020MLST....2..386N. doi: 10.1007/s42995-020-00065-9 .
  24. ↑ Whittaker VP (1990). "The Contribution of Drugs and Toxins to Understanding of Cholinergic Function" (PDF). Trends in Pharmacological Sciences. 11 (1): 8–13. doi:10.1016/0165-6147(90)90034-6. hdl: 11858/00-001M-0000-0013-0E8C-5 . PMID   2408211.
  25. ↑ Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia AS, McNamara JO, et al. (2008). Neuroscience (4th ed.). Sinauer Associates. pp. 121–122. ISBN   978-0-87893-697-7.
  26. ↑ English BA, Webster AA (2012). "Acetylcholinesterase and its Inhibitors". Primer on the Autonomic Nervous System. Elsevier. pp. 631–633. doi:10.1016/b978-0-12-386525-0.00132-3. ISBN   978-0-12-386525-0.
  27. ↑ "National Pesticide Information Center-Diazinon Technical Fact Sheet" (PDF). Retrieved February 24, 2012.
  28. ↑ "Clinical Application: Acetylcholine and Alzheimer's Disease" . Retrieved February 24, 2012.
  29. ↑ Stoelting RK (1999). Anticholinesterase Drugs and Cholinergic Agonists", in Pharmacology and Physiology in Anesthetic Practice. Lippincott-Raven. ISBN   978-0-7817-5469-9. Archived from the original on March 3, 2016. Retrieved February 26, 2012.
  30. ↑ Taylor P, Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG (1996). "5: Autonomic Pharmacology: Cholinergic Drugs". The Pharmacologial Basis of Therapeutics. THe McGraw-Hill Companies. pp. 161–174. ISBN   978-0-07-146804-6. Archived from the original on March 4, 2016. Retrieved February 26, 2012.
  31. ↑ Blumenthal D, Brunton L, Goodman LS, Parker K, Gilman A, Lazo JS, et al. (1996). "5: Autonomic Pharmacology: Cholinergic Drugs". Goodman & Gilman's The pharmacological basis of therapeutics. New York: McGraw-Hill. p. 1634. ISBN   978-0-07-146804-6.
  32. ↑ Drachman DB, Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, et al. (1998). Harrison's Principles of Internal Medicine (14 ed.). The McCraw-Hill Companies. pp.  2469–2472. ISBN   978-0-07-020291-7.
  33. ↑ Raffe RB (2004). Autonomic and Somatic Nervous Systems in Netter's Illustrated Pharmacology. Elsevier Health Science. p. 43. ISBN   978-1-929007-60-8.
  34. ↑ Shaked I, Meerson A, Wolf Y, Avni R, Greenberg D, Gilboa-Geffen A, et al. (2009). "MicroRNA-132 potentiates cholinergic anti-inflammatory signaling by targeting acetylcholinesterase". Immunity. 31 (6): 965–73. doi: 10.1016/j.immuni.2009.09.019 . PMID   20005135.
  35. ↑ Eubanks LM, Rogers CJ, Beuscher AE, Koob GF, Olson AJ, Dickerson TJ, et al. (2006). "A molecular link between the active component of marijuana and Alzheimer's disease pathology". Mol. Pharm. 3 (6): 773–7. doi:10.1021/mp060066m. PMC   2562334 . PMID   17140265.
  36. ↑ Massoulié J, Pezzementi L, Bon S, Krejci E, Vallette FM (July 1993). "Molecular and cellular biology of cholinesterases". Progress in Neurobiology. 41 (1): 31–91. doi:10.1016/0301-0082(93)90040-Y. PMID   8321908. S2CID   21601586.
  37. ↑ Chacko LW, Cerf JA (1960). "Histochemical localization of cholinesterase in the amphibian spinal cord and alterations following ventral root section". Journal of Anatomy. 94 (Pt 1): 74–81. PMC   1244416 . PMID   13808985.
  38. ↑ Koelle GB (1954). "The histochemical localization of cholinesterases in the central nervous system of the rat". Journal of Comparative Neurology. 100 (1): 211–35. doi:10.1002/cne.901000108. PMID   13130712. S2CID   23021010.
  39. ↑ Bartels CF, Zelinski T, Lockridge O (May 1993). "Mutation at codon 322 in the human acetylcholinesterase (ACHE) gene accounts for YT blood group polymorphism". Am. J. Hum. Genet. 52 (5): 928–36. PMC   1682033 . PMID   8488842.
  40. ↑ Johnson G, Moore SW (2012). "Why has butyrylcholinesterase been retained? Structural and functional diversification in a duplicated gene. 2012". Neurochem. Int. 16 (5): 783–797. doi:10.1016/j.neuint.2012.06.016. PMID   22750491. S2CID   39348660.
  41. ↑ Massoulié J, Perrier N, Noureddine H, Liang D, Bon S (2008). "Old and new questions about cholinesterases". Chem. Biol. Interact. 175 (1–3): 30–44. Bibcode:2008CBI...175...30M. doi:10.1016/j.cbi.2008.04.039. PMID   18541228.
  42. ↑ "Entrez Gene: ACHE acetylcholinesterase (Yt blood group)".
  43. ↑ Dori A, Ifergane G, Saar-Levy T, Bersudsky M, Mor I, Soreq H, et al. (2007). "Readthrough acetylcholinesterase in inflammation-associated neuropathies". Life Sci. 80 (24–25): 2369–74. doi:10.1016/j.lfs.2007.02.011. PMID   17379257.
  44. ↑ Millard CB, Kryger G, Ordentlich A, Greenblatt HM, Harel M, Raves ML, et al. (June 1999). "Crystal structures of aged phosphonylated acetylcholinesterase: nerve agent reaction products at the atomic level". Biochemistry. 38 (22): 7032–9. doi:10.1021/bi982678l. PMID   10353814. S2CID   11744952.
  45. ↑ Julien RM, Advokat CD, Comaty JE (October 12, 2007). A Primer of Drug Action (Eleventh ed.). Worth Publishers. pp.  50. ISBN   978-1-4292-0679-2.
  46. ↑ Macht VA, Woodruff JL, Maissy ES, Grillo CA, Wilson MA, Fadel JR, et al. (August 2019). "Pyridostigmine bromide and stress interact to impact immune function, cholinergic neurochemistry and behavior in a rat model of Gulf War Illness". Brain, Behavior, and Immunity. 80: 384–393. doi:10.1016/j.bbi.2019.04.015. PMC   6790976 . PMID   30953774.
  47. ↑ Puopolo T, Liu C, Ma H, Seeram NP (April 19, 2022). "Inhibitory Effects of Cannabinoids on Acetylcholinesterase and Butyrylcholinesterase Enzyme Activities". Medical Cannabis and Cannabinoids. 5 (1): 85–94. doi: 10.1159/000524086 . PMC   9149358 . PMID   35702400.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.