56-12-2 Usage
Description
4-Aminobutyric acid (GABA) is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system. In humans, GABA is also directly responsible for the regulation of muscle tone. Although chemically it is an amino acid, GABA is rarely referred to as such in the scientific or medical communities, because the term "amino acid," used without a qualifier, conventionally refers to the alpha amino acids, which GABA is not, nor is it ever incorporated into a protein. In spastic diplegia in humans, GABA absorption becomes impaired by nerves damaged from the condition's upper motor neuron lesion, which leads to hypertonia of the muscles signaled by those nerves that can no longer absorb GABA.
Chemical Properties
4-Aminobutyric acid is a white flake or needle-like crystal; slightly odorous, deliquescence; easily soluble in water, slightly soluble in hot ethanol, insoluble in cold ethanol, ether and benzene; decomposition point is 202°C; LD50 (rat, abdominal cavity) 5400mg/kg.
History
4-Aminobutyric acid was first synthesized in 1883, and was first known only as a plant and microbe metabolic product. In 1950, however, GABA was discovered to be an integral part of the mammalian central nervous system.
Uses
4-Aminobutyric acid is an important inhibitory neurotransmitter in the central nervous system, which has good water solubility and thermal stability. It has been confirmed that GABA, as a small molecular weight non protein amino acid, has edible safety and can be used in the production of beverages and other foods. Studies have shown that a certain amount of GABA can improve the body's sleep quality and reduce blood pressure.The foods contain γ-aminobutyric acid (GABA) at an amount that shows immediate effect of suppressing autonomic nerve activity related to blood pressure increase. Reacts with isothiocyanates to produce thioureas which have antifungal activity.
Preparation
The synthesis of 4-aminobutyric acid mainly includes the following: the first is the use of potassium Phthaloyl imine and γ- Chloroprene cyanogen or butyrolactone is used as the raw material of GABA. The final product obtained after violent reaction and hydrolysis is GABA; The second is to use pyrrolidone as the initial raw material, hydrolyze it through calcium hydroxide and ammonium bicarbonate, and finally open its ring to obtain GABA; The third is to use butyric acid and ammonia as raw materials of GABA γ GABA was obtained by light reaction under X-ray conditions; The fourth method is to synthesize GABA with propylamine and formic acid by glow discharge; The fifth is to use methyl bromoacetate and ethylene as raw materials to prepare GABA. Methyl 4-bromobutyrate is obtained through polymerization. Finally, the product after ammonolysis and hydrolysis is GABA. The chemical synthesis methods of GABA have the disadvantages of difficult reaction control and high cost.
Definition
ChEBI: Gamma-aminobutyric acid is a gamma-amino acid that is butanoic acid with the amino substituent located at C-4. It has a role as a signalling molecule, a human metabolite, a Saccharomyces cerevisiae metabolite and a neurotransmitter. It is a gamma-amino acid and a monocarboxylic acid. It derives from a butyric acid. It is a conjugate acid of a gamma-aminobutyrate. It is a tautomer of a gamma-aminobutyric acid zwitterion.
Aroma threshold values
Medium strength odor; savory meaty type; recommend smelling in a 1.00% solution or less.
Biological Functions
Neuro transmitter In vertebrates, GABA acts at inhibitory synapses in the brain by binding to specific transmembrane receptors in the plasma membrane of both pre- and postsynaptic neuronal processes. This binding causes the opening of ion channels to allow the flow of either negatively charged chloride ions into the cell or positively charged potassium ions out of the cell. This action results in a negative change in the transmembrane potential, usually causing hyperpolarization. Two general classes of GABA receptor are known: GABAA in which the receptor is part of a ligand-gated ion channel complex, and GABAB metabotropic receptors, which are G protein-coupled receptors that open or close ion channels via intermediaries (G proteins).Neurons that produce GABA as their output are called GABAergic neurons, and have chiefly inhibitory action at receptors in the adult vertebrate. Medium Spiny Cells are a typical example of inhibitory CNS GABAergic cells. In contrast, GABA exhibits both excitatory and inhibitory actions in insects, mediating muscle activation at synapses between nerves and muscle cells, and also the stimulation of certain glands. In mammals, some GABAergic neurons, such as chandelier cells, are also able to excite their glutamatergic counterparts.Brain developmentWhile GABA is an inhibitory transmitter in the mature brain, its actions are primarily excitatory in the developing brain. The gradient of chloride is reversed in immature neurons, and its reversal potential is higher than the resting membrane potential of the cell; activation of a GABA-A receptor thus leads to efflux of Cl- ions from the cell, i.e. a depolarizing current. The differential gradient of chloride in immature neurons is primarily due to the higher concentration of NKCC1 co-transporters relative to KCC2 cotransporters in immature cells. GABA itself is partially responsible for orchestrating the maturation of ion pumps . GABA-ergic interneurons mature faster in the hippocampus and the GABA signalling machinery appears earlier than glutamatergic transmission. Thus, GABA is the major excitatory neurotransmitter in many regions of the brain before the maturation of glutamateergic synapses.Beyond the nervous systemGABAergic mechanisms have been demonstrated in various peripheral tissues and organs including, but not restricted to the intestine, stomach, pancreas, Fallopian tube, uterus, ovary, testis, kidney, urinary bladder, lung, and liver.
General Description
4-Aminobutyric acid is a chief inhibitory neurotransmitter, which is found in the cerebellum, hypothalamus, thalamus and hippocampus. It is formed via the decarboxylation of L-glutamate catalyzed by the enzyme, glutamic acid decarboxylase(GAD).
Mechanism of action
4-Aminobutyric acid (GABA) probably represents the most important inhibitory transmitter of the mammalian CNS. Both types of GABAergic inhibition (pre- and postsynaptic) use the same GABAA
receptor subtype, which acts by regulation of the chloride channel of the neuronal membrane. A second GABA
receptor type, GABAB, that is a G protein–coupled receptor is not considered to be important in understanding
the mechanism of hypnotics. Activation of a GABAA receptor by an agonist increases the inhibitory synaptic
response of central neurons to GABA through hyperpolarization. Because many, if not all, central neurons
receive some GABAergic input, this leads to a mechanism by which CNS activity can be depressed. For
example, if the GABAergic interneurons are activated by an agonist that inhibits the monoaminergic structures
of the brainstem, hypnotic activity will be observed. The specific neuronal structures in different brain regions
affected by GABAA agonist continues to be better defined.
Pharmacology
Drugs that act as allosteric modulators of GABA receptors (known as GABA analogues or GABAergic drugs) or increase the available amount of GABA typically have relaxing, anti-anxiety, and anti-convulsive effects. Many of the substances below are known to cause anterograde amnesia and retrograde amnesia. In general, GABA does not cross the blood–brain barrier, although certain areas of the brain that have no effective blood–brain barrier, such as the periventricular nucleus, can be reached by drugs such as systematically injected GABA. At least one study suggests that orally administered GABA increases the amount of Human Growth Hormone. GABA directly injected to the brain has been reported to have both stimulatory and inhibitory effects on the production of growth hormone, depending on the physiology of the individual.
Metabolism
GABA transaminase enzyme catalyzes the conversion of 4- aminobutanoic acid and 2-oxoglutarate into succinic semialdehyde and glutamate. Succinic semialdehyde is then oxidized into succinic acid by succinic semialdehyde dehydrogenase and as such enters the citric acid cycle as a usable source of energy.
Purification Methods
Crystallise GABA from aqueous EtOH or MeOH/Et2O. Also crystallise it by dissolving it in the least volume of H2O and adding 5-7 volumes of absolute EtOH.
GABA as a supplement
A number of commercial sources sell formulations of GABA for use as a dietary supplement, sometimes for sublingual administration. These sources typically claim that the supplement has a calming effect. These claims are not yet scientifically proven. For example, there is evidence stating that the calming effects of GABA can be seen observably in the human brain after administration of GABA as an oral supplement. However, there is also evidence that GABA does not cross the blood – brain barrier at significant levels. There are some over-the-counter supplements such as phenylated GABA itself directly, or Phenibut; and Picamilon (both Soviet cosmonaut products) – Picamilon combines niacin and phenylated GABA and crosses the blood–brain barrier as a prodrug that later hydrolyzes into GABA and niacin.
Structure and conformation
4-Aminobutyric acid (GABA) is found mostly as a zwitterion, that is, with the carboxy group deprotonated and the amino group protonated. Its conformation depends on its environment. In the gas phase, a highly folded conformation is strongly favored because of the electrostatic attraction between the two functional groups. The stabilization is about 50 kcal/mol, according to quantum chemistry calculations. In the solid state, a more extended conformation is found, with a trans conformation at the amino end and a gauche conformation at the carboxyl end. This is due to the packing interactions with the neighboring molecules. In solution, five different conformations, some folded and some extended, are found as a result of solvation effects. The conformational flexibility of GABA is important for its biological function, as it has been found to bind to different receptors with different conformations. Many GABA analogues with pharmaceutical applications have more rigid structures in order to control the binding better.
Check Digit Verification of cas no
The CAS Registry Mumber 56-12-2 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 6 respectively; the second part has 2 digits, 1 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 56-12:
(4*5)+(3*6)+(2*1)+(1*2)=42
42 % 10 = 2
So 56-12-2 is a valid CAS Registry Number.
InChI:InChI=1/C4H9NO2/c5-3-1-2-4(6)7/h1-3,5H2,(H,6,7)
56-12-2Relevant articles and documents
Enhancing effect of macroporous adsorption resin on gamma-aminobutyric acid production by Enterococcus faecium in whole-cell biotransformation system
Yang, Sheng-Yuan,Liu, Shu-Min,Jiang, Min,Wang, Biao-Shi,Peng, Luo-Hui,Zeng, Chan
, p. 771 - 780 (2020)
Gamma-aminobutyric acid (GABA) biosynthesis depended to a great extent on the biotransformation characterization of glutamate decarboxylase (GAD) and process conditions. In this paper, the enhancing effect of D101 macroporous adsorption resin (MAR) on the GABA production was investigated based on the whole-cell biotransformation characterization of Enterococcus faecium and adsorption characteristics of D101 MAR. The results indicated that the optimal pH for reaction activity of whole-cell GAD and pure GAD was 4.4 and 5.0, respectively, and the pH range retained at least 50% of GAD activity was from 4.8 to 5.6 and 4.0–4.8, respectively. No substrate inhibition effect was observed on both pure GAD and whole-cell GAD, and the maximum activity could be obtained when the initial L-glutamic acid (L-Glu) concentration exceeded 57.6?mmol/L and 96.0?mmol/L, respectively. Besides, GABA could significantly inhibit the activity of whole-cell GAD rather than pure GAD. When the initial GABA concentration of the reaction solution remained 100?mmol/L, 33.51 ± 9.11% of the whole-cell GAD activity was inhibited. D101 MAR exhibited excellent properties in stabilizing the pH of the conversion reaction system, supplementing free L-Glu and removing excess GABA. Comparison of the biotransformation only in acetate buffer, the GABA production, with 50?g/100?mL of D101 MAR, was significantly increased by 138.71 ± 5.73%. D101 MAR with pre-adsorbed L-Glu could significantly enhance the production of GABA by gradual replenishment of free L-Glu, removing GABA and maintaining the pH of the reaction system, which would eventually make the GABA production more economical and eco-friendly.
ENZYMATIC SYNTHESIS OF γ-AMINOBUTYRIC ACID USING IMMOBILIZED L-GLUTAMATE DECARBOXYLASE
Yanushyavichyute, R. P.,Paulyukonis, A. B.,Kazlauskas, D. A.
, p. 246 (1983)
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Mechanistic aspects of uncatalyzed and ruthenium(III) catalyzed oxidation of DL-ornithine monohydrochloride by silver(III) periodate complex in aqueous alkaline medium
Malode, Shweta J.,Abbar, Jyothi C.,Nandibewoor, Sharanappa T.
, p. 2430 - 2442 (2010)
The oxidation of an amino acid, DL-ornithine monohydrochloride (OMH) by diperiodatoargentate(III) (DPA) was carried out both in the absence and presence of ruthenium(III) catalyst in alkaline medium at 25°C and a constant ionic strength of 0.10 mol dm-3 spectrophorometrically. The reaction was of first order in both catalyzed and uncatalyzed cases, with respect to [DPA] and was less than unit order in [OMH] and negative fraction in [alkali]. The order with respect to [OMH] changes from first order to zero order as the [OMH] increases. The order with respect to Ru(III) was unity. The uncatalyzed reaction in alkaline medium has been shown to proceed via a DPA-OMH complex, which decomposes in a rate determining step to give the products. Where as in catalyzed reaction, it has been shown to proceed via a Ru(III)-OMH complex, which further reacts with two molecules of DPA in a rate determining step to give the products. The reaction constants involved in the different steps of the mechanisms were calculated for both the reactions. The catalytic constant (Kcat.const.) was also calculated for catalyzed reaction at different temperatures. The activation parameters with respect to slow step of the mechanism and also the thermodynamic quantities were determined.
Lactams in sulfuric acid. The mechanism of amide hydrolysis in weak to moderately strong aqueous mineral acid media
Cox, Robin A.
, p. 649 - 656 (1998)
Reaction rate constants obtained in moderately concentrated sulfuric acid for the hydrolysis of simple lactams of ring sizes five, six, seven, and eight as a function of acidity and temperature have been analyzed using the excess acidity kinetic method. The basicity constants for these substrates have been recalculated; the 13C NMR spectra used to obtain these values are very sensitive to medium effects. It was found that the basicities of the lactams at 0.003-0.1 M lactam concentration were over half a pK unit more basic than they were at 0.5 M lactam, presumably because of the medium effect. Apart from this, the rate constant results obtained at different times by different groups using different techniques for monitoring the kinetics are in adequate agreement. The excess acidity analysis showed that the kinetics could be fitted according to the 'three-water-molecule followed by one-water-molecule' mechanistic scenario previously found, or could just as well be fitted by a 'one-water-molecule followed by unknown mechanism' scenario, with the mechanistic change taking place at 50 wt.% sulfuric acid for all the substrates. Other evidence makes the latter seem the more likely possibility of the two, and activation parameters based upon the 'one-water- molecule' process were determined. Sufficient data points to enable the unknown mechanism to be established were not present; possible mechanisms applicable in media more concentrated than 50 wt.% sulfuric acid are discussed. Previously obtained values of the parameter r, the number of water molecules involved with the substrate in A2 processes, are now questionable.
Osmium(VIII) catalyzed oxidation of DL-ornithine monohydrochloride by a new oxidant, diperiodatoargentate(III) in aqueous alkaline medium
Malode, Shweta J.,Abbar, Jyothi C.,Nandibewoor, Sharanappa T.
, p. 246 - 256 (2010)
The kinetics of osmium(VIII) (Os(VIII)) catalyzed oxidation of DL-ornithine monohydrochloride (OMH) by diperiodatoargentate(III) (DPA) in alkaline medium at 298 K and a constant ionic strength of 0.10 mol dm-3 was studied spectrophotometrically. The stoichiometry is, i.e., [OMH]:[DPA] [image omitted] 1:2. The main products were identified by spot tests, IR, 1H NMR, GC-MS spectral studies. A suitable mechanism is proposed. The reaction constants involved in the different steps of the mechanism are calculated. The catalytic constant (Kc) was also calculated for Os(VIII) catalysis at different temperatures. The active species of catalyst and oxidant have been identified. Copyright Taylor & Francis Group, LLC.
Kinetic and mechanistic aspects of osmium(VIII) catalyzed oxidation of DLornithine by copper(iii) periodate complex in aqueous alkaline medium
Abbar, Jyothi C.,Malode, Shweta J.,Nandibewoor, Sharanappa T.
, p. 865 - 882 (2010)
The oxidation of DL-ornithine monohydrochloride (OMH) by diperiodatocuprate(III) (DPC) has been investigated in the presence of osmium(VIII) catalyst in aqueous alkaline medium at a constant ionic strength of 0.20 mol dm-3 spectrophotometrically. The reaction exhibits 1:4 stoichiometry i.e., [OMH]: [DPC]. The order of the reaction with respect to [DPC] was unity while the order with respect to [OMH] was less than unity over the concentration range studied. The rate increased with an increase in [OH -] and decreased with an increase in [IO4-]. The order with respect to [Os(VIII)] was unity. The reaction rates revealed that Os(VIII) catalyzed reaction was about nine-fold faster than the uncatalyzed reaction. The oxidation products were identified by spectral analysis. Suitable mechanism has been proposed. The reaction constants involved in the different steps of the reaction mechanism were calculated. The catalytic constant (KC) was also calculated at different temperatures. The activation parameters with respect to slow step of the mechanism and also the thermodynamic quantities were determined. Kinetic experiments suggest that [OsO4(OH) 2]2- is the reactive Os(VIII) species and [Cu(H 2IO6)(H2O)2] is the reactive copper(III) species. by Oldenbourg Wissenschaftsverlag, Muenchen.
METHODS AND MATERIALS FOR ASSESSING AND TREATING OBESITY
-
, (2021/03/13)
This document relates to methods and materials for assessing and/or treating obese mammals (e.g., obese humans). For example, methods and materials for using one or more interventions (e.g., one or more pharmacological interventions) to treat obesity and/or obesity-related comorbidities in a mammal (e.g., a human) identified as being likely to respond to a particular intervention (e.g., a pharmacological intervention) are provided.
METHODS FOR IMPROVING YIELDS OF L-GLUFOSINATE
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Page/Page column 33, (2020/03/29)
Compositions and methods for the production of L-glufosinate are provided. The method involves converting racemic glufosinate to the L-glufosinate enantiomer or converting PRO to L-glufosinate in an efficient manner. In particular, the method involves the specific amination of PRO to L-glufosinate, using L-glutamate, racemic glutamate, or another amine source as an amine donor. PRO can be obtained by the oxidative deamination of D-glufosinate to PRO (2- oxo-4-(hydroxy(methyl)phosphinoyl)butyric acid) or generated via chemical synthesis. PRO is then converted to L-glufosinate using a transaminase in the presence of an amine donor. When the amine donor donates an amine to PRO, L-glufosinate and a reaction by product are formed. Because the PRO remaining represents a yield loss of L-glufosinate, it is desirable to minimize the amount of PRO remaining in the reaction mixture. Degradation, other chemical modification, extraction, sequestration, binding, or other methods to reduce the effective concentration of the by-product, i.e., the corresponding alpha ketoacid or ketone to the chosen amine donor will shift the reaction equilibrium toward L-glufosinate, thereby reducing the amount of PRO and increasing the yield of L-glufosinate. Therefore, the methods described herein involve the conversion or elimination of the alpha ketoacid or ketone by-product to another product to shift the equilibrium towards L-glufosinate.