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77-441: Acetylcholine ( ACh ) is an organic compound that functions in the brain and body of many types of animals (including humans) 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 . Acetylcholine is the neurotransmitter used at the neuromuscular junction —in other words, it

154-420: A black widow spider , one experiences the wastage of ACh supplies and the muscles begin to contract. If and when the supply is depleted, paralysis occurs. Acetylcholine is used by organisms in all domains of life for a variety of purposes. It is believed that choline , a precursor to acetylcholine, was used by single celled organisms billions of years ago for synthesizing cell membrane phospholipids. Following

231-462: A second messenger system . The M1, M3, and M5 subtypes are G q -coupled; they increase intracellular levels of IP 3 and calcium by activating phospholipase C . Their effect on target cells is usually excitatory. The M2 and M4 subtypes are G i /G o -coupled; they decrease intracellular levels of cAMP by inhibiting adenylate cyclase . Their effect on target cells is usually inhibitory. Muscarinic acetylcholine receptors are found in both

308-412: A common homolog, these receptors evolved from separate receptor families. It is estimated that the nicotinic receptor family dates back longer than 2.5 billion years. Likewise, muscarinic receptors are thought to have diverged from other GPCRs at least 0.5 billion years ago. Both of these receptor groups have evolved numerous subtypes with unique ligand affinities and signaling mechanisms. The diversity of

385-436: 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

462-424: A high affinity for sulfhydryl groups , which causes dysfunction of the enzyme choline acetyltransferase. This inhibition may lead to acetylcholine deficiency, and can have consequences on motor function. Botulinum toxin (Botox) acts by suppressing the release of acetylcholine, whereas the venom from a black widow spider ( alpha-latrotoxin ) has the reverse effect. ACh inhibition causes paralysis . When bitten by

539-474: A regulative force must exist within living bodies. Berzelius also contended that compounds could be distinguished by whether they required any organisms in their synthesis (organic compounds) or whether they did not ( inorganic compounds ). Vitalism taught that formation of these "organic" compounds were fundamentally different from the "inorganic" compounds that could be obtained from the elements by chemical manipulations in laboratories. Vitalism survived for

616-411: A sequence of steps that finally produce muscle contraction . Factors that decrease release of acetylcholine (and thereby affecting P-type calcium channels ): Calcium channel blockers (nifedipine, diltiazem) do not affect P-channels. These drugs affect L-type calcium channels . The autonomic nervous system controls a wide range of involuntary and unconscious body functions. Its main branches are

693-452: A short period after the formulation of modern ideas about the atomic theory and chemical elements . It first came under question in 1824, when Friedrich Wöhler synthesized oxalic acid , a compound known to occur only in living organisms, from cyanogen . A further experiment was Wöhler's 1828 synthesis of urea from the inorganic salts potassium cyanate and ammonium sulfate . Urea had long been considered an "organic" compound, as it

770-675: A similar manner when in contact with tissue lysates that contained acetylcholine-degrading enzymes (now known to be cholinesterases ). This conclusion was accepted widely. Later studies confirmed the function of acetylcholine as a neurotransmitter . In 1936, H. H. Dale and O. Loewi shared the Nobel Prize in Physiology or Medicine for their studies of acetylcholine and nerve impulses. Organic compound Due to carbon's ability to catenate (form chains with other carbon atoms ), millions of organic compounds are known. The study of

847-404: A single element and so not generally considered chemical compounds . The word "organic" in this context does not mean "natural". Vitalism was a widespread conception that substances found in organic nature are formed from the chemical elements by the action of a "vital force" or "life-force" ( vis vitalis ) that only living organisms possess. In the 1810s, Jöns Jacob Berzelius argued that

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924-634: A small percentage of Earth's crust , they are of central importance because all known life is based on organic compounds. Living things incorporate inorganic carbon compounds into organic compounds through a network of processes ( the carbon cycle ) that begins with the conversion of carbon dioxide and a hydrogen source like water into simple sugars and other organic molecules by autotrophic organisms using light ( photosynthesis ) or other sources of energy. Most synthetically-produced organic compounds are ultimately derived from petrochemicals consisting mainly of hydrocarbons , which are themselves formed from

1001-426: 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

1078-421: A transition metal and to oxygen, and are often prepared directly from metal and carbon monoxide . Nickel tetracarbonyl is typically classified as an organometallic compound as it satisfies the broad definition that organometallic chemistry covers all compounds that contain at least one carbon to metal covalent bond; it is unknown whether organometallic compounds form a subset of organic compounds. For example,

1155-1692: A variety of ways. One major distinction is between natural and synthetic compounds. Organic compounds can also be classified or subdivided by the presence of heteroatoms , e.g., organometallic compounds , which feature bonds between carbon and a metal , and organophosphorus compounds , which feature bonds between carbon and a phosphorus . Another distinction, based on the size of organic compounds, distinguishes between small molecules and polymers . Natural compounds refer to those that are produced by plants or animals. Many of these are still extracted from natural sources because they would be more expensive to produce artificially. Examples include most sugars , some alkaloids and terpenoids , certain nutrients such as vitamin B 12 , and, in general, those natural products with large or stereoisometrically complicated molecules present in reasonable concentrations in living organisms. Further compounds of prime importance in biochemistry are antigens , carbohydrates , enzymes , hormones , lipids and fatty acids , neurotransmitters , nucleic acids , proteins , peptides and amino acids , lectins , vitamins , and fats and oils . Compounds that are prepared by reaction of other compounds are known as " synthetic ". They may be either compounds that are already found in plants/animals or those artificial compounds that do not occur naturally . Most polymers (a category that includes all plastics and rubbers ) are organic synthetic or semi-synthetic compounds. Many organic compounds—two examples are ethanol and insulin —are manufactured industrially using organisms such as bacteria and yeast. Typically,

1232-506: 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

1309-413: Is "rest and digest" or "feed and breed". Both of these aforementioned systems use acetylcholine, but in different ways. At a schematic level, the sympathetic and parasympathetic nervous systems are both organized in essentially the same way: preganglionic neurons in the central nervous system send projections to neurons located in autonomic ganglia, which send output projections to virtually every tissue of

1386-972: Is any compound that contains a significant amount of carbon—even though many of the organic compounds known today have no connection to any substance found in living organisms. The term carbogenic has been proposed by E. J. Corey as a modern alternative to organic , but this neologism remains relatively obscure. The organic compound L -isoleucine molecule presents some features typical of organic compounds: carbon–carbon bonds , carbon–hydrogen bonds , as well as covalent bonds from carbon to oxygen and to nitrogen. As described in detail below, any definition of organic compound that uses simple, broadly-applicable criteria turns out to be unsatisfactory, to varying degrees. The modern, commonly accepted definition of organic compound essentially amounts to any carbon-containing compound, excluding several classes of substances traditionally considered "inorganic". The list of substances so excluded varies from author to author. Still, it

1463-584: 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

1540-710: Is generally agreed upon that there are (at least) a few carbon-containing compounds that should not be considered organic. For instance, almost all authorities would require the exclusion of alloys that contain carbon, including steel (which contains cementite , Fe 3 C ), as well as other metal and semimetal carbides (including "ionic" carbides, e.g, Al 4 C 3 and CaC 2 and "covalent" carbides, e.g. B 4 C and SiC , and graphite intercalation compounds, e.g. KC 8 ). Other compounds and materials that are considered 'inorganic' by most authorities include: metal carbonates , simple oxides of carbon ( CO , CO 2 , and arguably, C 3 O 2 ),

1617-463: 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

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1694-618: 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

1771-431: Is introduced externally, it remains in the extracellular space and at present it is considered that the molecule does not pass through the blood–brain barrier. Acetylcholine is synthesized in certain neurons by the enzyme choline acetyltransferase from the compounds choline and acetyl-CoA . Cholinergic neurons are capable of producing ACh. An example of a central cholinergic area is the nucleus basalis of Meynert in

1848-402: 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

1925-479: Is on a carbon atom. For historical reasons discussed below, a few types of carbon-containing compounds, such as carbides , carbonates (excluding carbonate esters ), simple oxides of carbon (for example, CO and CO 2 ) and cyanides are generally considered inorganic compounds . Different forms ( allotropes ) of pure carbon, such as diamond , graphite , fullerenes and carbon nanotubes are also excluded because they are simple substances composed of

2002-517: 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,

2079-406: 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

2156-418: Is the chemical that motor neurons of the nervous system release in order to activate muscles. This property means that drugs that affect cholinergic systems can have very dangerous effects ranging from paralysis to convulsions . Acetylcholine is also a neurotransmitter in the autonomic nervous system , both as an internal transmitter for both the sympathetic and the parasympathetic nervous system , and as

2233-478: 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

2310-421: 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

2387-434: 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

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2464-1113: The DNA of an organism is altered to express compounds not ordinarily produced by the organism. Many such biotechnology -engineered compounds did not previously exist in nature. A great number of more specialized databases exist for diverse branches of organic chemistry. The main tools are proton and carbon-13 NMR spectroscopy , IR Spectroscopy , Mass spectrometry , UV/Vis Spectroscopy and X-ray crystallography . Acetylcholinesterase 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 ,

2541-781: The allotropes of carbon, cyanide derivatives not containing an organic residue (e.g., KCN , (CN) 2 , BrCN , cyanate anion OCN , etc.), and heavier analogs thereof (e.g., cyaphide anion CP , CSe 2 , COS ; although carbon disulfide CS 2 is often classed as an organic solvent). Halides of carbon without hydrogen (e.g., CF 4 and CClF 3 ), phosgene ( COCl 2 ), carboranes , metal carbonyls (e.g., nickel tetracarbonyl ), mellitic anhydride ( C 12 O 9 ), and other exotic oxocarbons are also considered inorganic by some authorities. Nickel tetracarbonyl ( Ni(CO) 4 ) and other metal carbonyls are often volatile liquids, like many organic compounds, yet they contain only carbon bonded to

2618-418: The carbamates ). Many toxins and venoms produced by plants and animals also contain cholinesterase inhibitors. In clinical use, they are administered in low doses to reverse the action of muscle relaxants , to treat myasthenia gravis , and to treat symptoms of Alzheimer's disease ( rivastigmine , which increases cholinergic activity in the brain). Organic mercurial compounds, such as methylmercury , have

2695-430: 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,

2772-423: 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

2849-522: The striatum , which is part of the basal ganglia . It is released by cholinergic interneurons . In humans, non-human primates and rodents, these interneurons respond to salient environmental stimuli with responses that are temporally aligned with the responses of dopaminergic neurons of the substantia nigra . Acetylcholine has been implicated in learning and memory in several ways. The anticholinergic drug scopolamine impairs acquisition of new information in humans and animals. In animals, disruption of

2926-416: The sympathetic nervous system and parasympathetic nervous system . Broadly speaking, the function of the sympathetic nervous system is to mobilize the body for action; the phrase often invoked to describe it is fight-or-flight . The function of the parasympathetic nervous system is to put the body in a state conducive to rest, regeneration, digestion, and reproduction; the phrase often invoked to describe it

3003-436: The synaptic cleft (the space between nerve and muscle). Blocking, hindering or mimicking the action of acetylcholine has many uses in medicine. Drugs acting on the acetylcholine system are either agonists to the receptors, stimulating the system, or antagonists, inhibiting it. Acetylcholine receptor agonists and antagonists can either have an effect directly on the receptors or exert their effects indirectly, e.g., by affecting

3080-411: The M 1 receptor subtype has been implicated in anticholinergic delirium. The addictive qualities of nicotine are derived from its effects on nicotinic acetylcholine receptors in the brain. Acetylcholine is a choline molecule that has been acetylated at the oxygen atom. Because of the charged ammonium group, acetylcholine does not penetrate lipid membranes. Because of this, when the molecule

3157-464: 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

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3234-416: The autonomic nervous system. Like many other biologically active substances, acetylcholine exerts its effects by binding to and activating receptors located on the surface of cells. There are two main classes of acetylcholine receptor, nicotinic and muscarinic . They are named for chemicals that can selectively activate each type of receptor without activating the other: muscarine is a compound found in

3311-445: The basal forebrain. The enzyme acetylcholinesterase converts acetylcholine into the inactive metabolites choline and acetate . This enzyme is abundant in the synaptic cleft, and its role in rapidly clearing free acetylcholine from the synapse is essential for proper muscle function. Certain neurotoxins work by inhibiting acetylcholinesterase, thus leading to excess acetylcholine at the neuromuscular junction , causing paralysis of

3388-517: The blood pressure of animals. In 1914, Arthur J. Ewins was the first to extract acetylcholine from nature. He identified it as the blood pressure-decreasing contaminant from some Claviceps purpurea ergot extracts, by the request of Henry Hallett Dale . Later in 1914, Dale outlined the effects of acetylcholine at various types of peripheral synapses and also noted that it lowered the blood pressure of cats via subcutaneous injections even at doses of one nanogram . The concept of neurotransmitters

3465-525: The body inappropriately produces antibodies against acetylcholine nicotinic receptors, and thus inhibits proper acetylcholine signal transmission. Over time, the motor end plate is destroyed. Drugs that competitively inhibit acetylcholinesterase (e.g., neostigmine , physostigmine , or primarily pyridostigmine ) are effective in treating the symptoms of this disorder. They allow endogenously released acetylcholine more time to interact with its respective receptor before being inactivated by acetylcholinesterase in

3542-424: The body. In both branches the internal connections, the projections from the central nervous system to the autonomic ganglia, use acetylcholine as a neurotransmitter to innervate (or excite) ganglia neurons. In the parasympathetic nervous system the output connections, the projections from ganglion neurons to tissues that do not belong to the nervous system, also release acetylcholine but act on muscarinic receptors. In

3619-436: The central nervous system and the peripheral nervous system of the heart, lungs, upper gastrointestinal tract, and sweat glands. Acetylcholine is the substance the nervous system uses to activate skeletal muscles , a kind of striated muscle. These are the muscles used for all types of voluntary movement, in contrast to smooth muscle tissue , which is involved in a range of involuntary activities such as movement of food through

3696-448: The electrical response is fast and short-lived. Curares are arrow poisons, which act at nicotinic receptors and have been used to develop clinically useful therapies. Muscarinic receptors form G protein-coupled receptor complexes in the cell membranes of neurons and other cells. Atropine is a non-selective competitive antagonist with Acetylcholine at muscarinic receptors. Many ACh receptor agonists work indirectly by inhibiting

3773-405: The enzyme acetylcholinesterase , which degrades the receptor ligand. Agonists increase the level of receptor activation; antagonists reduce it. Acetylcholine itself does not have therapeutic value as a drug for intravenous administration because of its multi-faceted action (non-selective) and rapid inactivation by cholinesterase. However, it is used in the form of eye drops to cause constriction of

3850-440: The enzyme acetylcholinesterase . The resulting accumulation of acetylcholine causes continuous stimulation of the muscles, glands, and central nervous system, which can result in fatal convulsions if the dose is high. They are examples of enzyme inhibitors , and increase the action of acetylcholine by delaying its degradation; some have been used as nerve agents ( Sarin and VX nerve gas) or pesticides ( organophosphates and

3927-595: 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

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4004-502: 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

4081-421: 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

4158-938: The evidence of covalent Fe-C bonding in cementite , a major component of steel, places it within this broad definition of organometallic, yet steel and other carbon-containing alloys are seldom regarded as organic compounds. Thus, it is unclear whether the definition of organometallic should be narrowed, whether these considerations imply that organometallic compounds are not necessarily organic, or both. Metal complexes with organic ligands but no carbon-metal bonds (e.g., (CH 3 CO 2 ) 2 Cu ) are not considered organometallic; instead, they are called metal-organic compounds (and might be considered organic). The relatively narrow definition of organic compounds as those containing C-H bonds excludes compounds that are (historically and practically) considered organic. Neither urea CO(NH 2 ) 2 nor oxalic acid (COOH) 2 are organic by this definition, yet they were two key compounds in

4235-565: The evolution of choline transporters, the abundance of intracellular choline paved the way for choline to become incorporated into other synthetic pathways, including acetylcholine production. Acetylcholine is used by bacteria, fungi, and a variety of other animals. Many of the uses of acetylcholine rely on its action on ion channels via GPCRs like membrane proteins. The two major types of acetylcholine receptors, muscarinic and nicotinic receptors, have convergently evolved to be responsive to acetylcholine. This means that rather than having evolved from

4312-704: The final product released by the parasympathetic nervous system. Acetylcholine is the primary neurotransmitter of the parasympathetic nervous system. In the brain, acetylcholine functions as a neurotransmitter and as a neuromodulator . The brain contains a number of cholinergic areas, each with distinct functions; such as playing an important role in arousal , attention , memory and motivation . Acetylcholine has also been found in cells of non-neural origins as well as microbes. Recently, enzymes related to its synthesis, degradation and cellular uptake have been traced back to early origins of unicellular eukaryotes. The protist pathogens Acanthamoeba spp. have shown evidence of

4389-449: The gastrointestinal tract and constriction of blood vessels. Skeletal muscles are directly controlled by motor neurons located in the spinal cord or, in a few cases, the brainstem . These motor neurons send their axons through motor nerves , from which they emerge to connect to muscle fibers at a special type of synapse called the neuromuscular junction . When a motor neuron generates an action potential , it travels rapidly along

4466-404: The high pressure and temperature degradation of organic matter underground over geological timescales. This ultimate derivation notwithstanding, organic compounds are no longer defined as compounds originating in living things, as they were historically. In chemical nomenclature, an organyl group , frequently represented by the letter R, refers to any monovalent substituent whose open valence

4543-550: The memory deficits associated with Alzheimer's disease . ACh has also been shown to promote REM sleep. In the brainstem acetylcholine originates from the Pedunculopontine nucleus and laterodorsal tegmental nucleus collectively known as the meso pontine tegmentum area or pontomesencephalotegmental complex. In the basal forebrain, it originates from the basal nucleus of Meynert and medial septal nucleus : In addition, ACh acts as an important internal transmitter in

4620-601: The mineral mellite ( Al 2 C 6 (COO) 6 ·16H 2 O ). A slightly broader definition of the organic compound includes all compounds bearing C-H or C-C bonds. This would still exclude urea. Moreover, this definition still leads to somewhat arbitrary divisions in sets of carbon-halogen compounds. For example, CF 4 and CCl 4 would be considered by this rule to be "inorganic", whereas CHF 3 , CHCl 3 , and C 2 Cl 6 would be organic, though these compounds share many physical and chemical properties. Organic compounds may be classified in

4697-523: The muscles needed for breathing and stopping the beating of the heart. Acetylcholine functions in both the central nervous system (CNS) and the peripheral nervous system (PNS). In the CNS, cholinergic projections from the basal forebrain to the cerebral cortex and hippocampus support the cognitive functions of those target areas. In the PNS, acetylcholine activates muscles and is a major neurotransmitter in

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4774-535: The mushroom Amanita muscaria ; nicotine is found in tobacco. Nicotinic acetylcholine receptors are ligand-gated ion channels permeable to sodium , potassium , and calcium ions. In other words, they are ion channels embedded in cell membranes, capable of switching from a closed to an open state when acetylcholine binds to them; in the open state they allow ions to pass through. Nicotinic receptors come in two main types, known as muscle-type and neuronal-type. The muscle-type can be selectively blocked by curare ,

4851-402: The nerve until it reaches the neuromuscular junction, where it initiates an electrochemical process that causes acetylcholine to be released into the space between the presynaptic terminal and the muscle fiber. The acetylcholine molecules then bind to nicotinic ion-channel receptors on the muscle cell membrane, causing the ion channels to open. Sodium ions then flow into the muscle cell, initiating

4928-517: The neuromuscular junction. Drugs that act on muscarinic acetylcholine receptors , such as atropine , can be poisonous in large quantities, but in smaller doses they are commonly used to treat certain heart conditions and eye problems. Scopolamine , or diphenhydramine , which also act mainly on muscarinic receptors in an inhibitory fashion in the brain (especially the M 1 receptor) can cause delirium , hallucinations , and amnesia through receptor antagonism at these sites. So far as of 2016, only

5005-579: The neuronal-type by hexamethonium . The main location of muscle-type receptors is on muscle cells, as described in more detail below. Neuronal-type receptors are located in autonomic ganglia (both sympathetic and parasympathetic), and in the central nervous system. Muscarinic acetylcholine receptors have a more complex mechanism, and affect target cells over a longer time frame. In mammals, five subtypes of muscarinic receptors have been identified, labeled M1 through M5. All of them function as G protein-coupled receptors , meaning that they exert their effects via

5082-417: 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

5159-553: The presence of ACh, which provides growth and proliferative signals via a membrane-located M 1 -muscarinic receptor homolog. Partly because of acetylcholine's muscle-activating function, but also because of its functions in the autonomic nervous system and brain, many important drugs exert their effects by altering cholinergic transmission. Numerous venoms and toxins produced by plants, animals, and bacteria, as well as chemical nerve agents such as sarin , cause harm by inactivating or hyperactivating muscles through their influences on

5236-647: The properties, reactions, and syntheses of organic compounds comprise the discipline known as organic chemistry . For historical reasons, a few classes of carbon-containing compounds (e.g., carbonate salts and cyanide salts ), along with a few other exceptions (e.g., carbon dioxide , and even hydrogen cyanide despite the fact it contains a carbon-hydrogen bond), are generally considered inorganic . Other than those just named, little consensus exists among chemists on precisely which carbon-containing compounds are excluded, making any rigorous definition of an organic compound elusive. Although organic compounds make up only

5313-414: The pupil during cataract surgery, which facilitates quick post-operational recovery. Nicotine binds to and activates nicotinic acetylcholine receptors , mimicking the effect of acetylcholine at these receptors. ACh opens a Na channel upon binding so that Na flows into the cell. This causes a depolarization, and results in an excitatory post-synaptic potential. Thus, ACh is excitatory on skeletal muscle;

5390-415: The receptor types enables acetylcholine to create varying responses depending on which receptor types are activated, and allow for acetylcholine to dynamically regulate physiological processes. ACh receptors are related to 5-HT3 ( serotonin ), GABA , and Glycine receptors , both in sequence and structure, strongly suggesting that they have a common evolutionary origin. In 1867, Adolf von Baeyer resolved

5467-478: The structures of choline and acetylcholine and synthesized them both, referring to the latter as acetylneurin in the study. Choline is a precursor for acetylcholine. Acetylcholine was first noted to be biologically active in 1906, when Reid Hunt (1870–1948) and René de M. Taveau found that it decreased blood pressure in exceptionally tiny doses. This was after Frederick Walker Mott and William Dobinson Halliburton noted in 1899 that choline injections decreased

5544-411: The supply of acetylcholine to the neocortex impairs the learning of simple discrimination tasks, comparable to the acquisition of factual information and disruption of the supply of acetylcholine to the hippocampus and adjacent cortical areas produces forgetfulness, comparable to anterograde amnesia in humans. The disease myasthenia gravis , characterized by muscle weakness and fatigue, occurs when

5621-406: The surrounding smooth muscle to relax, leading to vasodilation . In the central nervous system, ACh has a variety of effects on plasticity, arousal and reward . ACh has an important role in the enhancement of alertness when we wake up, in sustaining attention and in learning and memory . Damage to the cholinergic (acetylcholine-producing) system in the brain has been shown to be associated with

5698-417: The sympathetic nervous system the output connections mainly release noradrenaline , although acetylcholine is released at a few points, such as the sudomotor innervation of the sweat glands. Acetylcholine in the serum exerts a direct effect on vascular tone by binding to muscarinic receptors present on vascular endothelium . These cells respond by increasing production of nitric oxide , which signals

5775-589: The vitalism debate. However, the IUPAC Blue Book on organic nomenclature specifically mentions urea and oxalic acid as organic compounds. Other compounds lacking C-H bonds but traditionally considered organic include benzenehexol , mesoxalic acid , and carbon tetrachloride . Mellitic acid , which contains no C-H bonds, is considered a possible organic compound in Martian soil. Terrestrially, it, and its anhydride, mellitic anhydride , are associated with

5852-445: Was known to occur only in the urine of living organisms. Wöhler's experiments were followed by many others, in which increasingly complex "organic" substances were produced from "inorganic" ones without the involvement of any living organism, thus disproving vitalism. Although vitalism has been discredited, scientific nomenclature retains the distinction between organic and inorganic compounds. The modern meaning of organic compound

5929-525: Was unknown until 1921, when Otto Loewi noted that the vagus nerve secreted a substance that inhibited the heart muscle whilst working as a professor in the University of Graz . He named it vagusstoff ("vagus substance"), noted it to be a structural analog of choline and suspected it to be acetylcholine. In 1926, Loewi and E. Navratil deduced that the compound is probably acetylcholine, as vagusstoff and synthetic acetylcholine lost their activity in

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