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55-591: 4EY7 , 4PQE , 1F8U , 3LII , 4BDT , 4M0E , 4M0F , 1VZJ , 2X8B , 1B41 , 4EY4 , 4EY5 , 4EY6 , 4EY8 , 5FOQ , 5HF9 , 5HF6 , 5FPQ , 5HF8 , 5HFA 43 11423 ENSG00000087085 ENSMUSG00000023328 P22303 P21836 NM_001367915 NM_001367917 NM_001367918 NM_001367919 NM_001290010 NM_009599 NP_001354846 NP_001354847 NP_001354848 NP_001276939 NP_033729 Acetylcholinesterase ( HGNC symbol ACHE ; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase ), also known as AChE, AChase or acetylhydrolase ,

110-400: A Wheland intermediate , in which (fourth) the conjugation of the ring is broken. He introduced the symbol C centered on the ring as a shorthand for the inner cycle , thus anticipating Erich Clar 's notation. It is argued that he also anticipated the nature of wave mechanics , since he recognized that his affinities had direction, not merely being point particles, and collectively having

165-440: A chemical characteristic in common, namely higher unsaturation indices than many aliphatic compounds , and Hofmann may not have been making a distinction between the two categories. In the 19th century chemists found it puzzling that benzene could be so unreactive toward addition reactions, given its presumed high degree of unsaturation. The cyclohexatriene structure for benzene was first proposed by August Kekulé in 1865. Over

220-406: A cyclic system of molecular orbitals, formed from p π atomic orbitals and populated in a closed shell by 4n (n is an integer) electrons, is given a single half-twist to correspond to a Möbius strip . A π system with 4n electrons in a flat (non-twisted) ring would be anti-aromatic, and therefore highly unstable, due to the symmetry of the combinations of p atomic orbitals. By twisting the ring,

275-432: A distribution that could be altered by introducing substituents onto the benzene ring ( much as the distribution of the electric charge in a body is altered by bringing it near to another body ). The quantum mechanical origins of this stability, or aromaticity, were first modelled by Hückel in 1931. He was the first to separate the bonding electrons into sigma and pi electrons. An aromatic (or aryl ) compound contains

330-430: A gorge leading to the active site. All 14 amino acids in the aromatic gorge are highly conserved across different species. Among the aromatic amino acids, tryptophan 84 is critical and its substitution with alanine results in a 3000-fold decrease in reactivity. The gorge is approximately 20 angstroms deep and five angstroms wide. The esteratic subsite, where acetylcholine is hydrolyzed to acetate and choline, contains

385-412: A manifestation of cyclic delocalization and of resonance . This is usually considered to be because electrons are free to cycle around circular arrangements of atoms that are alternately single- and double- bonded to one another. These bonds may be seen as a hybrid of a single bond and a double bond, each bond in the ring identical to every other. This commonly seen model of aromatic rings, namely

440-449: A new, weakly bonding orbital (and also creates a weakly antibonding orbital). Hence, cyclobutadiene is non-aromatic; the strain of the asymmetric configuration outweighs the anti-aromatic destabilization that would afflict the symmetric, square configuration. Aromatic compounds play key roles in the biochemistry of all living things. The four aromatic amino acids histidine , phenylalanine , tryptophan , and tyrosine each serve as one of

495-427: A set of covalently bound atoms with specific characteristics: Whereas benzene is aromatic (6 electrons, from 3 double bonds), cyclobutadiene is not, since the number of π delocalized electrons is 4, which of course is a multiple of 4. The cyclobutadienide (2−) ion, however, is aromatic (6 electrons). An atom in an aromatic system can have other electrons that are not part of the system, and are therefore ignored for

550-470: A single gene. A marked example is CAP which can refer to any of 6 different genes ( BRD4 Archived 2013-10-27 at the Wayback Machine , CAP1 Archived 2013-11-02 at the Wayback Machine , HACD1 Archived 2013-10-07 at the Wayback Machine , LNPEP Archived 2012-09-13 at the Wayback Machine , SERPINB6 Archived 2013-10-08 at the Wayback Machine , and SORBS1 Archived 2012-10-12 at

605-475: A standardized gene name after establishment of a consensus can create confusion, therefore the merit of this is controversial. For this reason the HGNC aims to change a gene name only if agreement for that change can be reached among a majority of researchers working on that gene. A complete list of all HGNC-approved gene symbols for protein-coding genes: Aromatic In organic chemistry , aromaticity

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660-424: 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. 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. The presence and role of AChE in bacteria

715-504: 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. It has also been shown that the main active ingredient in cannabis, tetrahydrocannabinol , is a competitive inhibitor of acetylcholinesterase. 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

770-478: Is a chemical property describing the way in which a conjugated ring of unsaturated bonds , lone pairs , or empty orbitals exhibits a stabilization stronger than would be expected by the stabilization of conjugation alone. The earliest use of the term was in an article by August Wilhelm Hofmann in 1855. There is no general relationship between aromaticity as a chemical property and the olfactory properties of such compounds. Aromaticity can also be considered

825-880: Is an even number, such as cyclotetradecaheptaene . In heterocyclic aromatics ( heteroaromats ), one or more of the atoms in the aromatic ring is of an element other than carbon. This can lessen the ring's aromaticity, and thus (as in the case of furan ) increase its reactivity. Other examples include pyridine , pyrazine , imidazole , pyrazole , oxazole , thiophene , and their benzannulated analogs ( benzimidazole , for example). Polycyclic aromatic hydrocarbons are molecules containing two or more simple aromatic rings fused together by sharing two neighboring carbon atoms (see also simple aromatic rings ). Examples are naphthalene , anthracene , and phenanthrene . Many chemical compounds are aromatic rings with other functional groups attached. Examples include trinitrotoluene (TNT), acetylsalicylic acid (aspirin), paracetamol , and

880-582: 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. 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). The major form of acetylcholinesterase found in brain, muscle, and other tissues, known as

935-565: Is found in homoaromaticity where conjugation is interrupted by a single sp ³ hybridized carbon atom. When carbon in benzene is replaced by other elements in borabenzene , silabenzene , germanabenzene , stannabenzene , phosphorine or pyrylium salts the aromaticity is still retained. Aromaticity also occurs in compounds that are not carbon-based at all. Inorganic 6-membered-ring compounds analogous to benzene have been synthesized. Hexasilabenzene (Si 6 H 6 ) and borazine (B 3 N 3 H 6 ) are structurally analogous to benzene, with

990-455: Is higher in motor neurons than in sensory neurons. Acetylcholinesterase is also found on the red blood cell membranes, where different forms constitute the Yt blood group antigens . 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. In mammals, acetylcholinesterase

1045-615: Is hypothesized in other species. It is thought to be involved in the stress response and, possibly, inflammation. The nomenclatural variations of ACHE and of cholinesterases generally are discussed at Cholinesterase § Types and nomenclature . For acetylcholine esterase (AChE), reversible inhibitors are those that do not irreversibly bond to and deactivate AChE. 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 . Exposure to acetylcholinesterase inhibitors

1100-409: Is indeed the earliest introduction of the term, it is curious that Hofmann says nothing about why he introduced an adjective indicating olfactory character to apply to a group of chemical substances only some of which have notable aromas. Also, many of the most odoriferous organic substances known are terpenes , which are not aromatic in the chemical sense. But terpenes and benzenoid substances do have

1155-400: Is not well-documented. 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. The liberated choline is taken up again by the pre-synaptic neuron and ACh

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1210-685: 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. HUGO Gene Nomenclature Committee Full gene names, and especially gene abbreviations and symbols, are often not specific to

1265-514: Is primarily involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter acetylcholine. 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. In plants, the biological functions of AChE are less clear, and its existence has been recognized by indirect evidence of its activity. For instance,

1320-464: Is shared by all six in the ring. Thus, there are not enough electrons to form double bonds on all the carbon atoms, but the "extra" electrons strengthen all of the bonds on the ring equally. The resulting molecular orbital has π symmetry. [REDACTED] The first known use of the word "aromatic" as a chemical term — namely, to apply to compounds that contain the phenyl radical — occurs in an article by August Wilhelm Hofmann in 1855. If this

1375-438: Is standard for resonance diagrams , a double-headed arrow is used to indicate that the two structures are not distinct entities, but merely hypothetical possibilities. Neither is an accurate representation of the actual compound, which is best represented by a hybrid (average) of these structures, which can be seen at right. A C=C bond is shorter than a C−C bond, but benzene is perfectly hexagonal—all six carbon-carbon bonds have

1430-403: Is synthesized by combining with acetyl-CoA through the action of choline acetyltransferase . A cholinomimetic drug disrupts this process by acting as a cholinergic neurotransmitter that is impervious to acetylcholinesterase's lysing action. Drugs or toxins that inhibit AChE lead to persistence of high concentrations of ACh within synapses, leading to increased cholinergic signaling within

1485-474: 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

1540-421: 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 : 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

1595-431: Is the primary target of inhibition by organophosphorus compounds such as nerve agents and pesticides . 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, approaching the limit allowed by diffusion of the substrate . The active site of AChE comprises two subsites—the anionic site and

1650-746: The Wayback Machine ). The HGNC short gene names, or gene symbols, unlike previously used or published symbols, are specifically assigned to one gene only. This can result in less common abbreviations being selected but reduces confusion as to which gene is referred to. The HGNC published its latest human gene naming guidelines in 2020. These may be summarized as: The HGNC states that "gene nomenclature should evolve with new technology rather than be restrictive, as sometimes occurs when historical and single gene nomenclature systems are applied." The HGNC has also issued guides to specific locus types such as endogenous retroviral loci, structural variants and non-coding RNAs. When assigning new gene nomenclature

1705-429: 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. The hydrolysis reaction of the carboxyl ester leads to the formation of an acyl-enzyme and free choline . Then,

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1760-421: The central nervous system , autonomic ganglia and neuromuscular junctions . 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. Cleavage of OP by AChE leaves a phosphoryl group in the esteratic site, which is slow to be hydrolyzed (on

1815-677: The 20 basic building-blocks of proteins. Further, all 5 nucleotides ( adenine , thymine , cytosine , guanine , and uracil ) that make up the sequence of the genetic code in DNA and RNA are aromatic purines or pyrimidines . The molecule heme contains an aromatic system with 22 π electrons. Chlorophyll also has a similar aromatic system. Aromatic compounds are important in industry. Key aromatic hydrocarbons of commercial interest are benzene , toluene , ortho -xylene and para -xylene . About 35 million tonnes are produced worldwide every year. They are extracted from complex mixtures obtained by

1870-492: The 4n + 2 rule. In furan , the oxygen atom is sp² hybridized. One lone pair is in the π system and the other in the plane of the ring (analogous to C-H bond on the other positions). There are 6 π electrons, so furan is aromatic. Aromatic molecules typically display enhanced chemical stability, compared to similar non-aromatic molecules. A molecule that can be aromatic will tend to alter its electronic or conformational structure to be in this situation. This extra stability changes

1925-421: The HGNC make efforts to contact authors who have published on the human gene in question by email, and their responses to the proposed nomenclature are requested. HGNC also coordinates with the related Mouse and Rat Genomic Nomenclature Committees, other database curators, and experts for given specific gene families or sets of genes. The gene name revision procedure is similar to the naming procedure, but changing

1980-457: The acyl-enzyme undergoes nucleophilic attack by a water molecule, assisted by the histidine 440 group, liberating acetic acid and regenerating the free enzyme. AChE is found in many biological species, including humans and other mammals, non-vertebrates, and plants. In humans, AChE is a cholinergic enzyme involved in the hydrolysis of the neurotransmitter acetylcholine (ACh) into its constituents, choline, and acetate. Overall, in mammals, AChE

2035-449: The carbon atoms replaced by another element or elements. In borazine, the boron and nitrogen atoms alternate around the ring. Quite recently, the aromaticity of planar Si 5 rings occurring in the Zintl phase Li 12 Si 7 was experimentally evidenced by Li solid state NMR. Metal aromaticity is believed to exist in certain metal clusters of aluminium. Möbius aromaticity occurs when

2090-474: The carbon nuclei — these are called σ-bonds . Double bonds consist of a σ-bond and a π-bond. The π-bonds are formed from overlap of atomic p-orbitals above and below the plane of the ring. The following diagram shows the positions of these p-orbitals: [REDACTED] Since they are out of the plane of the atoms, these orbitals can interact with each other freely, and become delocalized. This means that, instead of being tied to one atom of carbon, each electron

2145-438: The chemistry of the molecule. Aromatic compounds undergo electrophilic aromatic substitution and nucleophilic aromatic substitution reactions, but not electrophilic addition reactions as happens with carbon-carbon double bonds. Many of the earliest-known examples of aromatic compounds, such as benzene and toluene, have distinctive pleasant smells. This property led to the term "aromatic" for this class of compounds, and hence

2200-583: The enzyme in the intercellular junction, ColQ for the neuromuscular junction and PRiMA for synapses. 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. The third type has, so far, only been found in Torpedo sp. and mice although it

2255-491: 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 . An endogenous inhibitor of AChE in neurons

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2310-419: The esteratic subsite. The structure and mechanism of action of AChE have been elucidated from the crystal structure of the enzyme. 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

2365-454: The idea that benzene was formed from a six-membered carbon ring with alternating single and double bonds (cyclohexatriene), was developed by Kekulé (see History section below). The model for benzene consists of two resonance forms, which corresponds to the double and single bonds superimposing to give rise to six one-and-a-half bonds. Benzene is a more stable molecule than would be expected without accounting for charge delocalization. As

2420-449: The inner cycle of affinity suffers disruption, the contiguous carbon-atoms to which nothing has been attached of necessity acquire the ethylenic condition". Here, Armstrong is describing at least four modern concepts. First, his "affinity" is better known nowadays as the electron , which was to be discovered only seven years later by J. J. Thomson. Second, he is describing electrophilic aromatic substitution , proceeding (third) through

2475-419: The next few decades, most chemists readily accepted this structure, since it accounted for most of the known isomeric relationships of aromatic chemistry. Between 1897 and 1906, J. J. Thomson , the discoverer of the electron, proposed three equivalent electrons between each carbon atom in benzene. An explanation for the exceptional stability of benzene is conventionally attributed to Sir Robert Robinson , who

2530-427: The nucleotides of DNA . Aromaticity is found in ions as well: the cyclopropenyl cation (2e system), the cyclopentadienyl anion (6e system), the tropylium ion (6e), and the cyclooctatetraene dianion (10e). Aromatic properties have been attributed to non-benzenoid compounds such as tropone . Aromatic properties are tested to the limit in a class of compounds called cyclophanes . A special case of aromaticity

2585-417: 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

2640-422: The refining of oil or by distillation of coal tar, and are used to produce a range of important chemicals and polymers, including styrene , phenol , aniline , polyester and nylon . The overwhelming majority of aromatic compounds are compounds of carbon, but they need not be hydrocarbons. Benzene , as well as most other annulenes ( cyclodecapentaene excepted) with the formula C n H n where n ≥ 4 and

2695-554: The ring atoms of one molecule are attracted to the slight negative charge of the aromatic system on another molecule. Planar monocyclic molecules containing 4n π electrons are called antiaromatic and are, in general, destabilized. Molecules that could be antiaromatic will tend to alter their electronic or conformational structure to avoid this situation, thereby becoming non-aromatic. For example, cyclooctatetraene (COT) distorts itself out of planarity, breaking π overlap between adjacent double bonds. Relatively recently, cyclobutadiene

2750-427: The same length , intermediate between that of a single and that of a double bond . A better representation is that of the circular π bond (Armstrong's inner cycle ), in which the electron density is evenly distributed through a π-bond above and below the ring. This model more correctly represents the location of electron density within the aromatic ring. The single bonds are formed with electrons in line between

2805-403: The same mechanism, the signals of protons located near the ring axis are shifted up-field. Aromatic molecules are able to interact with each other in so-called π-π stacking : The π systems form two parallel rings overlap in a "face-to-face" orientation. Aromatic molecules are also able to interact with each other in an "edge-to-face" orientation: The slight positive charge of the substituents on

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2860-445: The symmetry of the system changes and becomes allowed (see also Möbius–Hückel concept for details). Because the twist can be left-handed or right-handed , the resulting Möbius aromatics are dissymmetric or chiral . As of 2012, there is no proof that a Möbius aromatic molecule was synthesized. Aromatics with two half-twists corresponding to the paradromic topologies were first suggested by Johann Listing . In carbo-benzene

2915-446: The term "aromaticity" for the eventually discovered electronic property. The circulating π electrons in an aromatic molecule produce ring currents that oppose the applied magnetic field in NMR . The NMR signal of protons in the plane of an aromatic ring are shifted substantially further down-field than those on non-aromatic sp² carbons. This is an important way of detecting aromaticity. By

2970-403: Was apparently the first (in 1925) to coin the term aromatic sextet as a group of six electrons that resists disruption. In fact, this concept can be traced further back, via Ernest Crocker in 1922, to Henry Edward Armstrong , who in 1890 wrote "the (six) centric affinities act within a cycle...benzene may be represented by a double ring ( sic ) ... and when an additive compound is formed,

3025-403: Was discovered to adopt an asymmetric, rectangular configuration in which single and double bonds indeed alternate; there is no resonance and the single bonds are markedly longer than the double bonds, reducing unfavorable p-orbital overlap. This reduction of symmetry lifts the degeneracy of the two formerly non-bonding molecular orbitals, which by Hund's rule forces the two unpaired electrons into

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