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.
Synthesis of the neurotransmitter 4-aminobutanoic acid (GABA) from diethyl cyanomalonate
Cook, Matthew C.,Witherell, Ross D.,White, Robert L.
, p. 9 - 13 (2010)
GABA was synthesized by deethoxycarbonylation, ester hydrolysis and nitrile reduction of a highly functionalized intermediate obtained by alkylation of diethyl cyanomalonate with ethyl bromoacetate. By judicious employment of D 2O or NaBD4 in one of the three functional group transformation steps, deuterium was selectively introduced into each of the three possible sites in GABA.
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.
Glutamate decarboxylase from Lactobacillus brevis: Activation by ammonium sulfate
Hiraga, Kazumi,Ueno, Yoshie,Oda, Kohei
, p. 1299 - 1306 (2008)
In this study, the glutamate decarboxylase (GAD) gene from Lactobacillus brevis IFO12005 (Biosci. Biotechnol. Biochem., 61, 1168-1171 (1997)), was cloned and expressed. The deduced amino acid sequence showed 99.6% and 53.1% identity with GAD of L. brevis ATCC367 and L. lactis respectively. The His-tagged recombinant GAD showed an optimum pH of 4.5-5.0, and 54 kDa on SDS-PAGE. The GAD activity and stability was significantly dependent on the ammonium sulfate concentration, as observed in authentic GAD. Gel filtration showed that the inactive form of the GAD was a dimer. In contrast, the ammonium sulfate-activated form was a tetramer. CD spectral analyses at pH 5.5 revealed that the structures of the tetramer and the dimer were similar. Treatment of the GAD with high concentrations of ammonium sulfate and subsequent dilution with sodium glutamate was essential for tetramer formation and its activation. Thus the biochemical properties of the GAD from L. brevis IFO12005 were significantly different from those from other sources.
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.
Augmentation of endogenous GABA pool size induced by Magainin II peptide
Boostan, Nona,Yazdanparast, Razieh
, p. 891 - 894 (2018)
Background: Gamma aminobutyric acid (GABA), an inhibitory neurotransmitter, is produced via decarboxylation of L-glutamate through the glutamic acid decarboxylase (GAD) enzyme. The synchronic action of GABA-transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH) enzymes convert the GABA metabolite into succinate. Given this background, our research was aimed at probing the effect of Magainin II, on the activity of GABA shunt metabolizing enzymes. Methods: Male NIH mice were administered peripherally by Magainin II (50 μg/kg body weight) and saline solution (%0.9 (w/v)) as the control vehicle. At different time intervals, the mice were sacrificed to evaluate the effect of Magainin II injection on the GABA shunt pathway. The activity of hypothalamic GAD, GABA-T and SSADH enzymes were determined using relevant enzyme assays. Results: Magainin II effectively enhanced the activity of GAD, by %90, 24 h after injection, while quenching the activities of GABA-T and SSADH by %43 and %71, respectively. In vitro models also revealed the direct but reversible interaction between the peptide and each of the individual enzymes of GABA shunt pathway. Conclusion: This study confirms the probable role of Magainin II in increasing the GABA content of the mouse hypothalamus. This property might candidate the peptide as a novel agent for improving the symptoms of many GABA dependent psychiatric disorders.
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.
Characterization of glutamate decarboxylase from a high γ-aminobutyric acid (GABA)-producer, Lactobacillus paracasei
Komatsuzaki, Noriko,Nakamura, Toshihide,Kimura, Toshinori,Shima, Jun
, p. 278 - 285 (2008)
γ-Aminobutyric acid (GABA) has several physiological functions in humans. We have reported that Lactobacillus paracasei NFRI 7415 produces high levels of GABA. To gain insight into the higher GABA-producing ability of this strain, we analyzed glutamate decarboxylase (GAD), which catalyzes the decarboxylation of L-glutamate to GABA. The molecular weight of the purified GAD was estimated to be 57 kDa by SDS-PAGE and 110 kDa by gel filtration, suggesting that GAD forms the dimer under native conditions. GAD activity was optimal at pH 5.0 at 50°C. The Km value for the catalysis of glutamate was 5.0 mM, and the maximum rate of catalysis was 7.5 μmol min-1 mg-1. The N-terminal amino acid sequence of GAD was determined, and the gene encoding GAD from genomic DNA was cloned. The findings suggest that the ability of Lb. paracasei to produce high levels of GABA results from two characteristics of GAD, viz., a low Km value and activity at low pH.
METHODS AND MATERIALS FOR ASSESSING AND TREATING OBESITY
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, (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.
