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Sample records for acetate succinate hpmcas

  1. Equilibrium state at supersaturated drug concentration achieved by hydroxypropyl methylcellulose acetate succinate: molecular characterization using (1)H NMR technique.

    PubMed

    Ueda, Keisuke; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2015-04-01

    The maintenance mechanism of the supersaturated state of poorly water-soluble drugs, glibenclamide (GLB) and chlorthalidone (CLT), in hydroxypropyl methylcellulose acetate succinate (HPMC-AS) solution was investigated at a molecular level. HPMC-AS suppressed drug crystallization from supersaturated drug solution and maintained high supersaturated level of drugs with small amount of HPMC-AS for 24 h. However, the dissolution of crystalline GLB into HPMC-AS solution failed to produce supersaturated concentrations, although supersaturated concentrations were achieved by adding amorphous GLB to HPMC-AS solution. HPMC-AS did not improve drug dissolution and/or solubility but efficiently inhibited drug crystallization from supersaturated drug solutions. Such an inhibiting effect led to the long-term maintenance of the amorphous state of GLB in HPMC-AS solution. NMR measurements showed that HPMC-AS suppressed the molecular mobility of CLT depending on their supersaturation level. Highly supersaturated CLT in HPMC-AS solution formed a gel-like structure with HPMC-AS in which the molecular mobility of the CLT was strongly suppressed. The gel-like structure of HPMC-AS could inhibit the reorganization from drug prenuclear aggregates to the crystal nuclei and delay the formation of drug crystals. The prolongation subsequently led to the redissolution of the aggregated drugs in aqueous solution and formed the equilibrium state at the supersaturated drug concentration in HPMC-AS solution. The equilibrium state formation of supersaturated drugs by HPMC-AS should be an essential mechanism underlying the marked drug concentration improvement. PMID:25723893

  2. The effect of HPMCAS functional groups on drug crystallization from the supersaturated state and dissolution improvement.

    PubMed

    Ueda, Keisuke; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2014-04-10

    The inhibitory effect on drug crystallization in aqueous solution was evaluated using various forms of hydroxypropyl methylcellulose acetate succinate (HPMCAS). HPMCAS suppressed crystallization of carbamazepine (CBZ), nifedipine (NIF), mefenamic acid, and dexamethasone. The inhibition of drug crystallization mainly derived from molecular level hydrophobic interactions between the drug and HPMCAS. HPMCAS with a lower succinoyl substituent ratio strongly suppressed drug crystallization. The inhibition of crystallization was affected by pH, with the CBZ crystallization being inhibited at a higher pH due to the hydrophilization of HPMCAS derived from succinoyl ionization. The molecular mobility of CBZ in an HPMCAS solution was evaluated by 1D-(1)H NMR and relaxation time measurements. CBZ mobility was strongly suppressed in the HPMCAS solutions where strong inhibitory effects on CBZ crystallization were observed. The mobility suppression of CBZ in the HPMCAS solution was derived from intermolecular interactions between CBZ and HPMCAS leading to an inhibition of crystallization. The effect of HPMCAS on the drug dissolution rate was evaluated using an NIF/HPMCAS solid dispersion. The dissolution rate of NIF was increased when HPMCAS with a higher succinoyl substituent ratio was used. PMID:24440403

  3. Preparation and Evaluation of Diclofenac Sodium Tablet Coated with Polyelectrolyte Multilayer Film Using Hypromellose Acetate Succinate and Polymethacrylates for pH-Dependent, Modified Release Drug Delivery.

    PubMed

    Jeganathan, Balamurugan; Prakya, Vijayalakshmi; Deshmukh, Abhijit

    2016-06-01

    Polyelectrolyte multilayer (PEM) film formed due to the electrostatic interaction between oppositely charged polyelectrolytes is of considerable interest because of their potential applications as both drug carriers and surface-modifying agents. In this study, in vitro studies were carried out on polyelectrolyte complexes formulated with Eudragit E (EE) and hypromellose acetate succinate (HPMCAS). The complexes of EE and HPMCAS were formulated by non-stoichiometric method. The prepared IPCs were investigated using Fourier transform infrared spectroscopy. Diclofenac sodium (DS) tablets were prepared and were coated with polymer solution of HPMCAS and EE to achieve pH-dependent and sustained-release tablets. Tablets were evaluated for their physical characteristics and in vitro drug release. The results of pharmacokinetic studies in rabbits showed that the selected formulation (F6) exhibited a delayed peak plasma concentration and marked sustained-release effect of drug in the in vivo drug release in comparison with marketed tablet. The suitable combination of PEM film based on EE and HPMCAS demonstrated potential candidate for targeted release of DS in the lower part of the gastrointestinal (GI) tract. PMID:26283195

  4. Absolute molecular weight determination of hypromellose acetate succinate by size exclusion chromatography: use of a multi angle laser light scattering detector and a mixed solvent.

    PubMed

    Chen, Raymond; Ilasi, Nicholas; Sekulic, Sonja S

    2011-12-01

    Molecular weight distribution is an important quality attribute for hypromellose acetate succinate (HPMCAS), a pharmaceutical excipient used in spray-dried dispersions. Our previous study showed that neither relative nor universal calibration method of size exclusion chromatography (SEC) works for HPMCAS polymers. We here report our effort to develop a SEC method using a mass sensitive multi angle laser light scattering detector (MALLS) to determine molecular weight distributions of HPMCAS polymers. A solvent screen study reveals that a mixed solvent (60:40%, v/v 50mM NaH(2)PO(4) with 0.1M NaNO(3) buffer: acetonitrile, pH* 8.0) is the best for HPMCAS-LF and MF sub-classes. Use of a mixed solvent creates a challenging condition for the method that uses refractive index detector. Therefore, we thoroughly evaluated the method performance and robustness. The mean weight average molecular weight of a polyethylene oxide standard has a 95% confidence interval of (28,443-28,793) g/mol vs. 28,700g/mol from the Certificate of Analysis. The relative standard deviations of average molecular weights for all polymers are 3-6%. These results and the Design of Experiments study demonstrate that the method is accurate and robust. PMID:21840663

  5. Stability-enhanced hot-melt extruded amorphous solid dispersions via combinations of Soluplus® and HPMCAS-HF.

    PubMed

    Alshahrani, Saad M; Lu, Wenli; Park, Jun-Bom; Morott, Joseph T; Alsulays, Bader B; Majumdar, Soumyajit; Langley, Nigel; Kolter, Karl; Gryczke, Andreas; Repka, Michael A

    2015-08-01

    The aim of this study was to evaluate a novel combination of Soluplus® and hypromellose acetate succinate (HPMCAS-HF) polymers for solubility enhancement as well as enhanced physicochemical stability of the produced amorphous solid dispersions. This was accomplished by converting the poorly water-soluble crystalline form of carbamazepine into a more soluble amorphous form within the polymeric blends. Carbamazepine (CBZ), a Biopharmaceutics Classification System class II active pharmaceutical ingredient (API) with multiple polymorphs, was utilized as a model drug. Hot-melt extrusion (HME) processing was used to prepare solid dispersions utilizing blends of polymers. Drug loading showed a significant effect on the dissolution rate of CBZ in all of the tested ratios of Soluplus® and HPMCAS-HF. CBZ was completely miscible in the polymeric blends of Soluplus® and HPMCAS-HF up to 40% drug loading. The extrudates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and dissolution studies. DSC and XRD data confirmed the formation of amorphous solid dispersions of CBZ in the polymeric blends of Soluplus® and HPMCAS-HF. Drug loading and release of CBZ was increased with Soluplus® (when used as the primary matrix polymer) when formulations contained Soluplus® with 7-21% (w/w) HPMCAS-HF. In addition, this blend of polymers was found to be physically and chemically stable at 40°C, 75% RH over 12 months without any dissolution rate changes. PMID:25567525

  6. Solubility parameters of hypromellose acetate succinate and plasticization in dry coating procedures.

    PubMed

    Klar, Fabian; Urbanetz, Nora Anne

    2016-10-01

    Solubility parameters of HPMCAS have not yet been investigated intensively. On this account, total and three-dimensional solubility parameters of HPMCAS were determined by using different experimental as well as computational methods. In addition, solubility properties of HPMCAS in a huge number of solvents were tested and a Teas plot for HPMCAS was created. The total solubility parameter of about 24 MPa(0.5) was confirmed by various procedures and compared with values of plasticizers. Twenty common pharmaceutical plasticizers were evaluated in terms of their suitability for supporting film formation of HPMCAS under dry coating conditions. Therefore, glass transition temperatures of mixtures of polymer and plasticizers were inspected and film formation of potential ones was further investigated in dry coating of pellets. Contact angles of plasticizers on HPMCAS were determined in order to give a hint of achievable coating efficiencies in dry coating, but none was found to spread on HPMCAS. A few common substances, e.g. dimethyl phthalate, glycerol monocaprylate, and polyethylene glycol 400, enabled plasticization of HPMCAS; however, only triethyl citrate and triacetin were found to be suitable for use in dry coating. Addition of acetylated monoglycerides to triacetin increased coating efficiency, which was likewise previously demonstrated for triethyl citrate. PMID:26925982

  7. [Elimination of succinate and acetate synthesis in recombinant Escherichia coli for D-lactate production].

    PubMed

    Zhou, Li; Tian, Kangming; Zuo, Zhirui; Chen, Xianzhong; Shi, Guiyang; Singh, Suren; Wang, Zhengxiang

    2011-01-01

    When Escherichia coli CICIM B0013-030 (B0013, ack-pta, pps, pflB) was used for D-lactate production, succinate and acetate were the main byproducts (as much as 11.9 and 7.1% the amount of lactate respectively). In order to decrease the byproduct levels, we inactivated succinate and acetate synthesis in B0013-030. Two recombinant plasmids containing mutation cassettes of frdA::difGm and tdcDE::difGm respectively were constructed first. The mutation cassettes were used to delete the target genes on the chromosomal by Red recombination. Subsequently, the antibiotic resistance gene was excised from the chromosomal by Xer recombination. Thereby, mutants B0013-040B (B0013-030, frdA) and B0013-050B (B0013-040B, tdcDE) were produced. D-lactate producing abilities of the engineered strains were tested both in shake flasks and in bioreactors using two-phase fermentation (aerobic growth and anaerobic fermentation) with glucose as the sole carbon source. When fermentation was carried out in shake flasks, inactivation of frdA in B0013-030 to produce B0013-040B reduced succinate accumulation by 80.8%. When tested in a 7-liter bioreactor, B0013-040B accumulated 114.5 g/L D-lactate of over 99.9% optical purity. However, 1.0 g/L succinate and 5.4 g/L acetate still remained in the broth. Further inactivation of tdcD and tdcE genes in B0013-040B to produce B0013-050B decreased acetate and succinate accumulation to 0.4 g/L and 0.4 g/L respectively, and lactate titer was as much as 111.9 g/L (tested in the 7-liter bioreactor). In lightof the lower byproduct levels and high lactate production, strain B00 13-050B may prove useful for D-lactate production. PMID:21553488

  8. Preparation and performance of hydroxypropyl methylcellulose esters of substituted succinates for in vitro supersaturation of a crystalline hydrophobic drug.

    PubMed

    Yin, Ligeng; Hillmyer, Marc A

    2014-01-01

    We prepared hydroxypropyl methylcellulose (HPMC) esters of substituted succinates and examined their performance for improving the aqueous solubility of crystalline hydrophobic drugs in spray-dried dispersions (SDDs). From one HPMC, we synthesized five HPMC esters using various monosubstituted succinic anhydrides. These HPMC esters along with a commercial HPMC acetate succinate (HPMCAS) were spray-dried from solutions with phenytoin. The SDDs with different matrices at 10 wt % loading had very similar bulk properties with a minimal amount of detectable crystalline phenytoin as revealed by scanning electron microscopy (SEM), powder X-ray diffraction (powder XRD), and differential scanning calorimetry (DSC). In solution, while the SDD with HPMCAS was very effective at achieving high levels of phenytoin supersaturation initially, it was not competent at maintaining such supersaturation due to the rapid crystallization of the dissolved phenytoin. Alternatively, SDDs with several synthesized HPMC esters of substituted succinates not only achieved rather high initial supersaturation but also maintained high concentrations for extended time (i.e., 1.5 h and longer). Such maintenance was largely ascribed to the inhibition of phenytoin nucleation. Structure-property relationships were established, and the most successful systems contained a high degree of substitution and a combination of a thioether with neighboring weak electron-withdrawing groups in the substituted succinic anhydrides. The effective maintenance of supersaturated solutions was only found in SDDs with rather low drug loadings, which indicates the significance of sufficiently high concentrations of polymer additives in the dissolution media. PMID:24320108

  9. Dynamics of three organic acids (malic, acetic and succinic acid) in sunflower exposed to cadmium and lead.

    PubMed

    Niu, Zhixin; Li, Xiaodong; Sun, Lina; Sun, Tieheng

    2013-01-01

    Sunflower (Helianthus annuus L.) has been considered as a good candidate for bioaccumulation of heavy metals. In the present study, sunflower was used to enrich the cadmium and lead in sand culture during 90 days. Biomass, Cd and Pb uptake, three organic acids and pH in cultures were investigated. Results showed that the existence of Cd and Pb showed different interactions on the organic acids exudation. In single Cd treatments, malic and acetic acids in Cd10 showed an incremental tendency with time. In the mixed treatments of Cd and Pb, malic acids increased when 10 and 40 mg x L(-1) Cd were added into Pb50, but acetic acids in Pb50 were inhibited by Cd addition. The Cd10 supplied in Pb10 stimulated the secretion of malic and succinic acids. Moreover, the Cd or Pb uptake in sunflower showed various correlations with pH and some organic acids, which might be due to the fact that the Cd and Pb interfere with the organic acids secretion in rhizosphere of sunflower, and the changes of organic acids altered the form and bioavailability of Cd and Pb in cultures conversely. PMID:23819268

  10. The Succinated Proteome

    SciTech Connect

    Merkley, Eric D.; Metz, Thomas O.; Smith, Richard D.; Baynes, John; Frizell, Norma

    2014-03-30

    Succination is a chemical modification of cysteine in protein by the Krebs cycle intermediate, fumarate, yielding S-(2-succino)cysteine (2SC). Intracellular fumarate concentration and succination of proteins are increased by hyperpolarization of the inner mitochondrial membrane, in concert with mitochondrial, endoplasmic reticulum (ER) and oxidative stress in adipocytes grown in high glucose medium and in adipose tissue in obesity and diabetes. Increased succination of proteins is also detected in the kidney of a fumarase conditional knock-out mouse which develops renal tumors. Keap1, the gatekeeper of the antioxidant response, was identified as a major succinated protein in renal cancer cells, suggesting that succination may play a role in activation of the antioxidant response. A wide range of proteins is subject to succination, including enzymes, adipokines, cytoskeletal proteins and ER chaperones with functional cysteine residues. There is also significant overlap between succinated and glutathionylated proteins, and with proteins containing cysteine residues that are readily oxidized to the sulfenic (cysteic) acid. Succination of adipocyte proteins is inhibited by uncouplers, which discharge the mitochondrial membrane potential (Δψm) and by ER stress inhibitors. 2SC serves as a biomarker of mitochondrial stress or dysfunction in chronic diseases, such as obesity, diabetes and cancer, and recent studies suggest that succination is a mechanistic link between mitochondrial dysfunction, oxidative and ER stress, and cellular progression toward apoptosis. In this article, we review the history of the succinated proteome and the challenges associated with measuring this non-enzymatic post-translational modification of proteins by proteomics approaches.

  11. THE SUCCINATED PROTEOME

    PubMed Central

    Merkley, Eric D.; Metz, Thomas O.; Smith, Richard D.; Baynes, John W.; Frizzell, Norma

    2014-01-01

    The post-translational modifications (PTMs) of cysteine residues include oxidation, S-glutathionylation, S-nitrosylation, and succination, all of which modify protein function or turnover in response to a changing intracellular redox environment. Succination is a chemical modification of cysteine in proteins by the Krebs cycle intermediate, fumarate, yielding S-(2-succino) cysteine (2SC). Intracellular fumarate concentration and succination of proteins are increased by hyperpolarization of the inner mitochondrial membrane, in concert with mitochondrial, endoplasmic reticulum (ER) and oxidative stress in 3T3 adipocytes grown in high glucose medium and in adipose tissue in obesity and diabetes in mice. Increased succination of proteins is also detected in the kidney of a fumarase deficient conditional knock-out mouse which develops renal cysts. A wide range of proteins are subject to succination, including enzymes, adipokines, cytoskeletal proteins, and ER chaperones with functional cysteine residues. There is also some overlap between succinated and glutathionylated proteins, suggesting that the same low pKa thiols are targeted by both. Succination of adipocyte proteins in diabetes increases as a result of nutrient excess derived mitochondrial stress and this is inhibited by uncouplers, which discharge the mitochondrial membrane potential (ΔΨm) and relieve the electron transport chain. 2SC therefore serves as a biomarker of mitochondrial stress or dysfunction in chronic diseases, such as obesity, diabetes, and cancer, and recent studies suggest that succination is a mechanistic link between mitochondrial dysfunction, oxidative and ER stress, and cellular progression toward apoptosis. In this article, we review the history of the succinated proteome and the challenges associated with measuring this non-enzymatic PTM of proteins by proteomics approaches. PMID:24115015

  12. Succinic anhydrides from epoxides

    SciTech Connect

    Coates, Geoffrey W.; Rowley, John M.

    2013-07-09

    Catalysts and methods for the double carbonylation of epoxides are disclosed. Each epoxide molecule reacts with two molecules of carbon monoxide to produce a succinic anhydride. The reaction is facilitated by catalysts combining a Lewis acidic species with a transition metal carbonyl complex. The double carbonylation is achieved in single process by using reaction conditions under which both carbonylation reactions occur without the necessity of isolating or purifying the product of the first carbonylation.

  13. Succinic anhydrides from epoxides

    SciTech Connect

    Coates, Geoffrey W; Rowley, John M

    2014-12-30

    Catalysts and methods for the double carbonylation of epoxides are disclosed. Each epoxide molecule reacts with two molecules of carbon monoxide to produce a succinic anhydride. The reaction is facilitated by catalysts combining a Lewis acidic species with a transition metal carbonyl complex. The double carbonylation is achieved in single process by using reaction conditions under which both carbonylation reactions occur without the necessity of isolating or purifying the product of the first carbonylation.

  14. Efficient aerobic succinate production from glucose in minimal medium with Corynebacterium glutamicum

    PubMed Central

    Litsanov, Boris; Kabus, Armin; Brocker, Melanie; Bott, Michael

    2012-01-01

    Summary Corynebacterium glutamicum, an established industrial amino acid producer, has been genetically modified for efficient succinate production from the renewable carbon source glucose under fully aerobic conditions in minimal medium. The initial deletion of the succinate dehydrogenase genes (sdhCAB) led to an accumulation of 4.7 g l−1 (40 mM) succinate as well as high amounts of acetate (125 mM) as by‐product. By deleting genes for all known acetate‐producing pathways (pta‐ackA, pqo and cat) acetate production could be strongly reduced by 83% and succinate production increased up to 7.8 g l−1 (66 mM). Whereas overexpression of the glyoxylate shunt genes (aceA and aceB) or overproduction of the anaplerotic enzyme pyruvate carboxylase (PCx) had only minor effects on succinate production, simultaneous overproduction of pyruvate carboxylase and PEP carboxylase resulted in a strain that produced 9.7 g l−1 (82 mM) succinate with a specific productivity of 1.60 mmol g (cdw)−1 h−1. This value represents the highest productivity among currently described aerobic bacterial succinate producers. Optimization of the production conditions by decoupling succinate production from cell growth using the most advanced producer strain (C. glutamicumΔpqoΔpta‐ackAΔsdhCABΔcat/pAN6‐pycP458Sppc) led to an additional increase of the product yield to 0.45 mol succinate mol−1 glucose and a titre of 10.6 g l−1 (90 mM) succinate. PMID:22018023

  15. Succinic acid production by Actinobacillus succinogenes from batch fermentation of mixed sugars.

    PubMed

    Almqvist, Henrik; Pateraki, Chrysanthi; Alexandri, Maria; Koutinas, Apostolis; Lidén, Gunnar

    2016-08-01

    Succinic acid production from the monosaccharides xylose, arabinose, glucose, mannose and galactose was studied using the bacterium Actinobacillus succinogenes. In Duran bottle cultures, containing 10 g/L of each of sugar, succinic acid was produced from all sugars except for galactose. The highest succinate yield, 0.56 g/g, was obtained with glucose, whereas the succinate yield was 0.42, 0.38 and 0.44 g/g for xylose, mannose and arabinose, respectively. The specific succinate productivity was 0.7 g/g h for glucose, but below 0.2 g/g h for the other sugars. Batch bioreactor fermentations were carried out using a sugar mixture of the five sugars giving a total concentration of 50 g/L, mimicking the distribution of sugars in spent sulfite liquor (SSL) from Eucalyptus which is rich in xylose. In this mixture, an almost complete conversion of all sugars (except galactose) was achieved resulting in a final succinate concentration of 21.8-26.8 g/L and a total yield of 0.59-0.68 g/g. There was evidence of co-consumption of glucose and xylose, whereas mannose was consumed after glucose. The main by-products were acetate 0.14-0.20 g/g and formate 0.08-0.13 g/g. NADH balance calculations suggested that NADH required for succinate production was not met solely from formate and acetate production, but other means of NADH production was necessary. Results from mixed sugar fermentations were verified using SSL as substrate resulting in a succinate yield of 0.60 g/g. In addition, it was found that CO2 sparging could replace carbonate supply in the form of MgCO3 without affecting the succinate yield. PMID:27255975

  16. Investigation of Phase Mixing in Amorphous Solid Dispersions of AMG 517 in HPMC-AS Using DSC, Solid-State NMR, and Solution Calorimetry.

    PubMed

    Calahan, Julie L; Azali, Stephanie C; Munson, Eric J; Nagapudi, Karthik

    2015-11-01

    Intimate phase mixing between the drug and the polymer is considered a prerequisite to achieve good physical stability for amorphous solid dispersions. In this article, spray dried amorphous dispersions (ASDs) of AMG 517 and HPMC-as were studied by differential scanning calorimetry (DSC), solid-state NMR (SSNMR), and solution calorimetry. DSC analysis showed a weakly asymmetric (ΔTg ≈ 13.5) system with a single glass transition for blends of different compositions indicating phase mixing. The Tg-composition data was modeled using the BKCV equation to accommodate the observed negative deviation from ideality. Proton spin-lattice relaxation times in the laboratory and rotating frames ((1)H T1 and T1ρ), as measured by SSNMR, were consistent with the observation that the components of the dispersion were in intimate contact over a 10-20 nm length scale. Based on the heat of mixing calculated from solution calorimetry and the entropy of mixing calculated from the Flory-Huggins theory, the free energy of mixing was calculated. The free energy of mixing was found to be positive for all ASDs, indicating that the drug and polymer are thermodynamically predisposed to phase separation at 25 °C. This suggests that miscibility measured by DSC and SSNMR is achieved kinetically as the result of intimate mixing between drug and polymer during the spray drying process. This kinetic phase mixing is responsible for the physical stability of the ASD. PMID:26457879

  17. Succinate production in Escherichia coli

    PubMed Central

    Thakker, Chandresh; Martínez, Irene; San, Ka-Yiu; Bennett, George N.

    2012-01-01

    Succinate has been recognized as an important platform chemical that can be produced from biomass. While a number of organisms are capable of succinate production naturally, this review focuses on the engineering of Escherichia coli for production of the four-carbon dicarboxylic acid. Important features of a succinate production system are to achieve optimal balance of reducing equivalents generated by consumption of the feedstock, while maximizing the amount of carbon that is channeled to the product. Aerobic and anaerobic production strains have been developed and applied to production from glucose as well as other abundant carbon sources. Metabolic engineering methods and strain evolution have been used and supplemented by the recent application of systems biology and in silico modeling tools to construct optimal production strains. The metabolic capacity of the production strain, as well as the requirement for efficient recovery of succinate and the reliability of the performance under scale-up are important in the overall process. The costs of the overall biorefinery compatible process will determine the economical commercialization of succinate and its impact in larger chemical markets. PMID:21932253

  18. 21 CFR 582.1091 - Succinic acid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Succinic acid. 582.1091 Section 582.1091 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1091 Succinic acid. (a) Product. Succinic acid. (b) Conditions of use. This substance is...

  19. 21 CFR 582.1091 - Succinic acid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Succinic acid. 582.1091 Section 582.1091 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1091 Succinic acid. (a) Product. Succinic acid. (b) Conditions of use. This substance is...

  20. 21 CFR 582.1091 - Succinic acid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Succinic acid. 582.1091 Section 582.1091 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1091 Succinic acid. (a) Product. Succinic acid. (b) Conditions of use. This substance is...

  1. 21 CFR 582.1091 - Succinic acid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Succinic acid. 582.1091 Section 582.1091 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1091 Succinic acid. (a) Product. Succinic acid. (b) Conditions of use. This substance is...

  2. 21 CFR 582.1091 - Succinic acid.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Succinic acid. 582.1091 Section 582.1091 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1091 Succinic acid. (a) Product. Succinic acid. (b) Conditions of use. This substance is...

  3. Improved Succinate Production by Metabolic Engineering

    PubMed Central

    Cheng, Ke-Ke; Wang, Gen-Yu; Zeng, Jing; Zhang, Jian-An

    2013-01-01

    Succinate is a promising chemical which has wide applications and can be produced by biological route. The history of the biosuccinate production shows that the joint effort of different metabolic engineering approaches brings successful results. In order to enhance the succinate production, multiple metabolical strategies have been sought. In this review, different overproducers for succinate production, including natural succinate overproducers and metabolic engineered overproducers, are examined and the metabolic engineering strategies and performances are discussed. Modification of the mechanism of substrate transportation, knocking-out genes responsible for by-products accumulation, overexpression of the genes directly involved in the pathway, and improvement of internal NADH and ATP formation are some of the strategies applied. Combination of the appropriate genes from homologous and heterologous hosts, extension of substrate, integrated production of succinate, and other high-value-added products are expected to bring a desired objective of producing succinate from renewable resources economically and efficiently. PMID:23691505

  4. 21 CFR 184.1091 - Succinic acid.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Succinic acid. 184.1091 Section 184.1091 Food and... Substances Affirmed as GRAS § 184.1091 Succinic acid. (a) Succinic acid (C4H6O4, CAS Reg. No. 110-15-6), also referred to as amber acid and ethylenesuccinic acid, is the chemical 1,4-butanedioic acid. It...

  5. 21 CFR 184.1091 - Succinic acid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Succinic acid. 184.1091 Section 184.1091 Food and... Substances Affirmed as GRAS § 184.1091 Succinic acid. (a) Succinic acid (C4H6O4, CAS Reg. No. 110-15-6), also referred to as amber acid and ethylenesuccinic acid, is the chemical 1,4-butanedioic acid. It...

  6. 21 CFR 184.1091 - Succinic acid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Succinic acid. 184.1091 Section 184.1091 Food and... Substances Affirmed as GRAS § 184.1091 Succinic acid. (a) Succinic acid (C4H6O4, CAS Reg. No. 110-15-6), also referred to as amber acid and ethylenesuccinic acid, is the chemical 1,4-butanedioic acid. It...

  7. 21 CFR 184.1091 - Succinic acid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Succinic acid. 184.1091 Section 184.1091 Food and... Substances Affirmed as GRAS § 184.1091 Succinic acid. (a) Succinic acid (C4H6O4, CAS Reg. No. 110-15-6), also referred to as amber acid and ethylenesuccinic acid, is the chemical 1,4-butanedioic acid. It...

  8. 21 CFR 184.1091 - Succinic acid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Succinic acid. 184.1091 Section 184.1091 Food and....1091 Succinic acid. (a) Succinic acid (C4H6O4, CAS Reg. No. 110-15-6), also referred to as amber acid and ethylenesuccinic acid, is the chemical 1,4-butanedioic acid. It is commercially prepared...

  9. Production of Succinic Acid for Lignocellulosic Hydrolysates

    SciTech Connect

    Davison, B.H.; Nghiem, J.

    2002-06-01

    The purpose of this Cooperative Research and Development Agreement (CRADA) is to add and test new metabolic activities to existing microbial catalysts for the production of succinic acid from renewables. In particular, they seek to add to the existing organism the ability to utilize xylose efficiently and simultaneously with glucose in mixtures of sugars or to add succinic acid production to another strain and to test the value of this new capability for production of succinic acid from industrial lignocellulosic hydrolyasates. The Contractors and Participant are hereinafter jointly referred to as the 'Parties'. Research to date in succinic acid fermentation, separation and genetic engineering has resulted in a potentially economical process based on the use of an Escherichia coli strain AFP111 with suitable characteristics for the production of succinic acid from glucose. Economic analysis has shown that higher value commodity chemicals can be economically produced from succinic acid based on repliminary laboratory findings and predicted catalytic parameters. The initial target markets include succinic acid itself, succinate salts, esters and other derivatives for use as deicers, solvents and acidulants. The other commodity products from the succinic acid platform include 1,4-butanediol, {gamma}-butyrolactone, 2-pyrrolidinone and N-methyl pyrrolidinone. Current economic analyses indicate that this platform is competitive with existing petrochemical routes, especially for the succinic acid and derivatives. The report presents the planned CRADA objectives followed by the results. The results section has a combined biocatalysis and fermentation section and a commercialization section. This is a nonproprietary report; additional proprietary information may be made available subject to acceptance of the appropriate proprietary information agreements.

  10. Effects of eliminating pyruvate node pathways and of coexpression of heterogeneous carboxylation enzymes on succinate production by Enterobacter aerogenes.

    PubMed

    Tajima, Yoshinori; Yamamoto, Yoko; Fukui, Keita; Nishio, Yousuke; Hashiguchi, Kenichi; Usuda, Yoshihiro; Sode, Koji

    2015-02-01

    Lowering the pH in bacterium-based succinate fermentation is considered a feasible approach to reduce total production costs. Newly isolated Enterobacter aerogenes strain AJ110637, a rapid carbon source assimilator under weakly acidic (pH 5.0) conditions, was selected as a platform for succinate production. Our previous work showed that the ΔadhE/PCK strain, developed from AJ110637 with inactivated ethanol dehydrogenase and introduced Actinobacillus succinogenes phosphoenolpyruvate carboxykinase (PCK), generated succinate as a major product of anaerobic mixed-acid fermentation from glucose under weakly acidic conditions (pH <6.2). To further improve the production of succinate by the ΔadhE/PCK strain, metabolically engineered strains were designed based on the elimination of pathways that produced undesirable products and the introduction of two carboxylation pathways from phosphoenolpyruvate and pyruvate to oxaloacetate. The highest production of succinate was observed with strain ES04/PCK+PYC, which had inactivated ethanol, lactate, acetate, and 2,3-butanediol pathways and coexpressed PCK and Corynebacterium glutamicum pyruvate carboxylase (PYC). This strain produced succinate from glucose with over 70% yield (gram per gram) without any measurable formation of ethanol, lactate, or 2,3-butanediol under weakly acidic conditions. The impact of lowering the pH from 7.0 to 5.5 on succinate production in this strain was evaluated under pH-controlled batch culture conditions and showed that the lower pH decreased the succinate titer but increased its yield. These findings can be applied to identify additional engineering targets to increase succinate production. PMID:25416770

  11. Single motoneuron succinate dehydrogenase activity.

    PubMed

    Chalmers, G R; Edgerton, V R

    1989-07-01

    We have developed a quantitative histochemical assay for measurement of succinate dehydrogenase (SDH) activity in single motoneurons. A computer image processing system was used to quantify the histochemical enzyme reaction product and to follow the time course of the reaction. The optimal concentration for each of the ingredients of the incubation medium for the SDH reaction was determined and the importance of using histochemical "blanks" in the determination of enzymatic activity was demonstrated. The enzymatic activity was linear with respect to reaction time and tissue thickness. The procedure described meets the criteria generally considered essential for establishment of a quantitative histochemical assay. The assay was then used to examine the SDH activity of cat and rat motoneurons. It was found that motoneurons with a small soma size had a wide range of SDH activity, whereas those with a large soma size were restricted to low SDH activity. PMID:2732457

  12. Advantage of Upregulation of Succinate Dehydrogenase in Staphylococcus aureus Biofilms ▿

    PubMed Central

    Gaupp, Rosmarie; Schlag, Steffen; Liebeke, Manuel; Lalk, Michael; Götz, Friedrich

    2010-01-01

    Previous studies have demonstrated that various tricarboxylic acid (TCA) cycle genes, particularly the succinate dehydrogenase genes (sdhCAB), are upregulated in Staphylococcus aureus biofilms. To better study the role of this enzyme complex, an sdhCAB deletion mutant (Δsdh) was constructed. Compared to the wild type (wt) the mutant was impaired in planktonic growth under aerobic conditions, excreted acetic acid could not be reused and accumulated continuously, succinate was excreted and found in the culture supernatant, and metabolome analysis with cells grown in chemically defined medium revealed reduced uptake/metabolism of some amino acids from the growth medium. Moreover, the mutant was able to counteract the steadily decreasing extracellular pH by increased urease activity. The addition of fumarate to the growth medium restored the wt phenotype. The mutant showed a small-colony variant (SCV)-like phenotype, a slight increase in resistance to various aminoglycoside antibiotics, and decreased pigmentation. The decreased growth under aerobic conditions is due to the interruption of the TCA cycle (indicated by the accumulation of succinate and acetic acid) with the consequence that many fewer reduction equivalents (NADH and FADH2) can fuel the respiratory chain. The results indicate that the TCA cycle is required for acetate and amino acid catabolism; its upregulation under biofilm conditions is advantageous under such nutrient- and oxygen-limited conditions. PMID:20207757

  13. Genetics Home Reference: succinic semialdehyde dehydrogenase deficiency

    MedlinePlus

    ... a chemical that transmits signals in the brain (neurotransmitter) called gamma-amino butyric acid (GABA). The primary ... Diseases National Organization for Rare Disorders (NORD) Pediatric Neurotransmitter Disease Association GeneReviews (1 link) Succinic Semialdehyde Dehydrogenase ...

  14. Role of succinic acid in chemical evolution

    NASA Technical Reports Server (NTRS)

    Negron-Mendoza, A.; Ponnamperuma, C.

    1982-01-01

    Succinic acid is converted into other carboxylic acids by ionizing radiation. The results obtained have been correlated with the ready formation of this compound in prebiotic experiments. Its role in biological systems may be related to its prebiotic occurrence.

  15. Ammonium acetate

    Integrated Risk Information System (IRIS)

    Ammonium acetate ; CASRN 631 - 61 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  16. Vinyl acetate

    Integrated Risk Information System (IRIS)

    Vinyl acetate ; CASRN 108 - 05 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  17. Ethyl acetate

    Integrated Risk Information System (IRIS)

    Ethyl acetate ; CASRN 141 - 78 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  18. Phenylmercuric acetate

    Integrated Risk Information System (IRIS)

    Phenylmercuric acetate ; CASRN 62 - 38 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinog

  19. Thallium acetate

    Integrated Risk Information System (IRIS)

    Jump to main content . Integrated Risk Information System Recent Additions | Contact Us Search : All EPA IRIS • You are here : EPA Home • Research • Environmental Assessment • IRIS • IRIS Summaries Redirect Page As of September 30 , 2009 , the assessment summary for Thallium acetate is included in t

  20. Manipulating redox and ATP balancing for improved production of succinate in E. coli.

    PubMed

    Singh, Amarjeet; Cher Soh, Keng; Hatzimanikatis, Vassily; Gill, Ryan T

    2011-01-01

    Redox and energy balance plays a key role in determining microbial fitness. Efforts to redirect bacterial metabolism often involve overexpression and deletion of genes surrounding key central metabolites, such as pyruvate and acetyl-coA. In the case of metabolic engineering of Escherichia coli for succinate production, efforts have mainly focused on the manipulation of key pyruvate metabolizing enzymes. E. coli AFP111 strain lacking ldhA, pflB and ptsG encoded activities accumulates acetate and ethanol as well as shows poor anaerobic growth on rich and minimal media. To address these issues, we first deleted genes (adhE, ackA-pta) involved in byproduct formation downstream of acetyl-CoA followed by the deletion of iclR and pdhR to activate the glyoxylate pathway. Based on data from these studies, we hypothesized that the succinate productivity was limited by the insufficient ATP generation. Genome-scale thermodynamics-based flux balance analysis indicated that overexpression of ATP-forming PEPCK from Actinobacillus succinogenes in an ldhA, pflB and ptsG triple mutant strain could result in an increase in biomass and succinate flux. Testing of this prediction confirmed that PEPCK overexpression resulted in a 60% increase in biomass and succinate formation in the ldhA, pflB, ptsG mutant strain. PMID:21040799

  1. Efficient production of succinic acid from Palmaria palmata hydrolysate by metabolically engineered Escherichia coli.

    PubMed

    Olajuyin, Ayobami Matthew; Yang, Maohua; Liu, Yilan; Mu, Tingzhen; Tian, Jiangnan; Adaramoye, Oluwatosin Adekunle; Xing, Jianmin

    2016-08-01

    Succinic acid, a C4 dicarboxylic acid is used in many fields such as food, agriculture, pharmaceutical and polymer industries. In this study, microbial production of succinic acid from Palmaria palmata was investigated for the first time. In engineered Escherichia coli KLPPP, lactate dehydrogenase, pyruvate formate lyase, phosphotransacetylase-acetate kinase and pyruvate oxidase genes were deleted while phosphoenolpyruvate carboxykinase was overexpressed. The recombinant exhibited higher molar yield of succinic acid on galactose (1.20±0.02mol/mol) than glucose (0.48±0.03mol/mol). The concentration and molar yield of succinic acid were 22.40±0.12g/L and 1.13±0.02mol/mol total sugar respectively after 72h dual phase fermentation from P. palmata hydrolysate which composed of glucose (12.57±0.17g/L) and galactose (18.03±0.10g/L). The results demonstrate that P. palmata red macroalgae biomass represents a novel and an economically alternative feedstock for biochemicals production. PMID:27203224

  2. Localization of the enzymes involved in the photoevolution of H sub 2 from acetate in Chlamydomonas reinhardtii

    SciTech Connect

    Willeford, K.O.; Gibbs, M. )

    1989-07-01

    The localization of a series of enzymes involved in the anaerobic photodissimilation of acetate in Chlamydomonas reinhardtii F-60 adapted to a hydrogen metabolism was determined through the enzymatic analyses of the chloroplastic, cytoplasmic, and mitochondrial fractions obtained with a cellular fractionation procedure that incorporated cell wall removal by treatment with autolysine, digestion of the plasmalemma with the detergent digitonin, and fractionation by differential centrifugation on a Percoll step gradient. The sequence of events leading to the photoevolution of H{sub 2} from acetate includes the conversion of acetate into succinate via the extraplastidic glyoxylate cycle, the oxidation of succinate to fumarate by chloroplastic succinate dehydrogenase, and the oxidation of malate to oxaloacetate in the chloroplast by NAD dependent malate dehydrogenase. The level of potential activity for the enzymes assayed were sufficient to accommodate the observed rate of the photoanaerobic dissimilation of acetate and the photoevolution of H{sub 2}.

  3. Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis.

    PubMed

    De Vadder, Filipe; Kovatcheva-Datchary, Petia; Zitoun, Carine; Duchampt, Adeline; Bäckhed, Fredrik; Mithieux, Gilles

    2016-07-12

    Beneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date, no study has focused on the role of succinate on host metabolism. Here, we fed mice a fiber-rich diet and found that succinate was the most abundant carboxylic acid in the cecum. Dietary succinate was identified as a substrate for intestinal gluconeogenesis (IGN), a process that improves glucose homeostasis. Accordingly, dietary succinate improved glucose and insulin tolerance in wild-type mice, but those effects were absent in mice deficient in IGN. Conventional mice colonized with the succinate producer Prevotella copri exhibited metabolic benefits, which could be related to succinate-activated IGN. Thus, microbiota-produced succinate is a previously unsuspected bacterial metabolite improving glycemic control through activation of IGN. PMID:27411015

  4. Recovery of succinic acid from fermentation broth.

    PubMed

    Kurzrock, Tanja; Weuster-Botz, Dirk

    2010-03-01

    Succinic acid is of high interest as bio-feedstock for the chemical industry. It is a precursor for a variety of many other chemicals, e.g. 1,4-butandiol, tetrahydrofuran, biodegradable polymers and fumaric acid. Besides optimized production strains and fermentation processes it is indispensable to develop cost-saving and energy-effective downstream processes to compete with the current petrochemical production process. Various methods such as precipitation, sorption and ion exchange, electrodialysis, and liquid-liquid extraction have been investigated for the recovery of succinic acid from fermentation broth and are reviewed critically here. PMID:19898782

  5. Conductance Studies of Aqueous Succinic Acid

    NASA Astrophysics Data System (ADS)

    Apelblat, Alexander; Barthel, Josef

    1992-03-01

    Conductance measurements of aqueous solutions of succinic acid and of di-sodium succinate were performed from 278.15 to 308.15 K and the limiting conductances λ0 (1/2 Succ2- ) are reported. The Waiden product is independent of temperature: λ0(1/2 Succ2-)*η(T) = 0.503 ± 0.001. The salt conductances closely obey the Onsager limiting law. The evaluation of the equilibrium constants for the primary and secondary steps of dissociation, K1 and K2, and the limiting conductances of the hydrosuccinate ion, λ0(HSucc-), are discussed using the Quint and Viallard conductance equation

  6. 21 CFR 522.1884 - Prednisolone sodium succinate injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Prednisolone sodium succinate injection. 522.1884... § 522.1884 Prednisolone sodium succinate injection. (a) Chemical name. 11 beta, 17, 21-Trihydroxypregna-1, 4-diene-3, 20-dione 21-succinate sodium salt. (b) Specifications. Each milliliter of...

  7. 21 CFR 522.1884 - Prednisolone sodium succinate injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Prednisolone sodium succinate injection. 522.1884... § 522.1884 Prednisolone sodium succinate injection. (a) Chemical name. 11 beta, 17, 21-Trihydroxypregna-1, 4-diene-3, 20-dione 21-succinate sodium salt. (b) Specifications. Each milliliter of...

  8. 21 CFR 520.784 - Doxylamine succinate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate as...

  9. 21 CFR 520.784 - Doxylamine succinate tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate as...

  10. 21 CFR 520.784 - Doxylamine succinate tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate as...

  11. 21 CFR 520.784 - Doxylamine succinate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate as...

  12. Activation of glyoxylate pathway without the activation of its related gene in succinate-producing engineered Escherichia coli.

    PubMed

    Zhu, Li-Wen; Li, Xiao-Hong; Zhang, Lei; Li, Hong-Mei; Liu, Jian-Hua; Yuan, Zhan-Peng; Chen, Tao; Tang, Ya-Jie

    2013-11-01

    For the first time, glyoxylate pathway in the biosynthesis of succinate was activated without the genetic manipulations of any gene related with glyoxylate pathway. Furthermore, the inactivation of succinate biosynthesis by-products genes encoding acetate kinase (ackA) and phosphotransacetylase (pta) was proven to be the key factor to activate glyoxylate pathway in the metabolically engineered Escherichia coli under anaerobic conditions. In order to enhance the succinate biosynthesis specifically, the genes (i.e., ldhA, ptsG, ackA-pta, focA-pflB, adhE) that disrupt by-products biosynthesis pathways were combinatorially deleted, while the E. coli malate dehydrogenase (MDH) was overexpression. The highest succinate production of 150.78 mM was obtained with YJ003 (ΔldhA, ptsG, ackA-pta), which were 5-folds higher than that obtained with wild type control strain DY329 (25.13 mM). For further understand the metabolic response as a result of several genetic manipulations, an anaerobic stoichiometric model that takes into account the glyoxylate pathway have successfully been implemented to estimate the intracellular fluxes in various recombinant E. coli. The fraction to the glyoxylate pathway from OAA in DY329 was 0 and 31% in YJ003, which indicated that even without the absence of the iclR mutation; the glyoxylate pathway was also activated by deleting the by-products biosynthetic genes, and to be responsible for the higher succinate yields. For further strengthen glyoxylate pathway, a two-stage fed-batch fermentation process was developed by using a 600 g l(-1) glucose feed to achieve a cell growth rate of 0.07 h(-1) in aerobic fermentation, and using a 750 g l(-1) glucose feed to maintain the residual glucose concentration around 40 g l(-1) when its residual level decreased to 10gl(-1) in anaerobic fermentation. The best mutant strain YJ003/pTrc99A-mdh produces final succinate concentration of 274 mM by fed-batch culture, which was 10-folds higher than that obtained

  13. Enhanced succinate production from glycerol by engineered Escherichia coli strains.

    PubMed

    Li, Qing; Wu, Hui; Li, Zhimin; Ye, Qin

    2016-10-01

    In this study, an engineered strain Escherichia coli MLB (ldhA(-)pflB(-)) was constructed for production of succinate from glycerol. The succinate yield was 0.37mol/mol in anaerobic culture, however, the growth and glycerol consumption rates were very slow, resulting in a low succinate level. Two-stage fermentation was performed in flasks, and the succinate yield reached 0.93mol/mol, but the succinate titer was still low. Hence, overexpression of malate dehydrogenase, malic enzyme, phosphoenolpyruvate (PEP) carboxylase and PEP carboxykinase (PCK) from E. coli, and pyruvate carboxylase from Corynebacterium glutamicum in MLB was investigated for improving succinate production. Overexpression of PCK resulted in remarkable enhancement of glycerol consumption and succinate production. In flask experiments, the succinate concentration reached 118.1mM, and in a 1.5-L bioreactor the succinate concentration further increased to 360.2mM. The highest succinate yield achieved 0.93mol/mol, which was 93% of the theoretical yield, in the anaerobic stage. PMID:27371794

  14. Succinate transport by free-living forms of Rhizobium japonicum.

    PubMed Central

    McAllister, C F; Lepo, J E

    1983-01-01

    We have demonstrated that the transport of succinate into the cells of Rhizobium japonicum strains USDA 110 and USDA 217 is severely inhibited by cyanide, azide, and 2,4-dinitrophenol, but not by arsenate. These results suggest an active mechanism of transport that is dependent on an energized membrane, but does not directly utilize ATP. The apparent Km for succinate was 3.8 microM for strain USDA 110 and 1.8 microM for strain USDA 217; maximal transport velocities were 1.5 and 3.3 nmol of succinate per min per mg of protein, respectively. The expression of the succinate uptake activity was inducible rather than constitutive, with succinate and structurally related compounds being the most effective inducers. The mechanism showed some specificity for succinate and similar organic acids; fumarate and L-malate were classical competitive inhibitors of the system. In general, the best competing compounds were also the best carbon substrates for induction of succinate uptake activity. EDTA inhibited the transport of succinate, implying a role for divalent cations in the system. When various divalent cations were used to reconstitute EDTA-inhibited activity, Ca2+ was most effective, followed by Mg2+, which restored activity at about half the efficiency of Ca2+. Growth media that were supplemented with increased Ca2+ concentration supported more rapid growth with succinate as the carbon substrate, and cells from such media showed higher specific activities of succinate transport. PMID:6402487

  15. Neuropathology in Succinic Semialdehyde Dehydrogenase Deficiency

    PubMed Central

    Knerr, Ina; Gibson, K. Michael; Murdoch, Geoffrey; Salomons, Gajja S.; Jakobs, Cornelis; Combs, Susan; Pearl, Phillip L.

    2010-01-01

    Reported here is the novel finding of neuropathology in a patient with succinic semialdehyde dehydrogenase deficiency, an inherited disorder of γ-aminobutyric acid metabolism characterized by intellectual deficiency, hypotonia, and epilepsy, with 4-hydroxybutyric aciduria and abnormalities of the globus pallidus on neuroimaging. A 19-year-old woman of European origin with a neurodevelopmental disorder and epilepsy died unexpectedly in 1998. A postmortem examination was performed, with a final diagnosis of sudden unexpected death in epilepsy patients. Eight years later, her sister with a neurodevelopmental disorder presented at 13 years of age with seizures and was diagnosed with succinic semialdehyde dehydrogenase deficiency. In the decedent, succinic semialdehyde dehydrogenase deficiency was established at the molecular level, 10 years after her death, using genomic DNA from brain tissue specimens. The neuropathologic findings revealed striking discoloration of the globi pallidi, leptomeningeal congestion, and a scar in the frontal cortex. After detection of the pathogenic homozygous mutation c.1226G>A, p.Gly409Asp in the living sister, it was confirmed in the decedent. An underlying metabolic disease may be an additional risk factor for sudden unexpected death in epilepsy patients. PMID:20304328

  16. Succinate dehydrogenase-deficient gastrointestinal stromal tumors

    PubMed Central

    Wang, Ya-Mei; Gu, Meng-Li; Ji, Feng

    2015-01-01

    Most gastrointestinal stromal tumors (GISTs) are characterized by KIT or platelet-derived growth factor alpha (PDGFRA) activating mutations. However, there are still 10%-15% of GISTs lacking KIT and PDGFRA mutations, called wild-type GISTs (WT GISTs). Among these so-called WT GISTs, a small subset is associated with succinate dehydrogenase (SDH) deficiency, known as SDH-deficient GISTs. In addition, GISTs that occur in Carney triad and Carney-Stratakis syndrome represent specific examples of SDH-deficient GISTs. SDH-deficient GISTs locate exclusively in the stomach, showing predilection for children and young adults with female preponderance. The tumor generally pursues an indolent course and exhibits primary resistance to imatinib therapy in most cases. Loss of succinate dehydrogenase subunit B expression and overexpression of insulin-like growth factor 1 receptor (IGF1R) are common features of SDH-deficient GISTs. In WT GISTs without succinate dehydrogenase activity, upregulation of hypoxia-inducible factor 1α may lead to increased growth signaling through IGF1R and vascular endothelial growth factor receptor (VEGFR). As a result, IGF1R and VEGFR are promising to be the novel therapeutic targets of GISTs. This review will update the current knowledge on characteristics of SDH-deficient GISTs and further discuss the possible mechanisms of tumorigenesis and clinical management of SDH-deficient GISTs. PMID:25741136

  17. Proteomic Analysis on Acetate Metabolism in Citrobacter sp. BL-4

    PubMed Central

    Kim, Young-Man; Lee, Sung-Eun; Park, Byeoung-Soo; Son, Mi-Kyung; Jung, Young-Mi; Yang, Seung-Ok; Choi, Hyung-Kyoon; Hur, Sung-Ho; Yum, Jong Hwa

    2012-01-01

    Mass production of glucosamine (GlcN) using microbial cells is a worthy approach to increase added values and keep safety problems in GlcN production process. Prior to set up a microbial cellular platform, this study was to assess acetate metabolism in Citrobacter sp. BL-4 (BL-4) which has produced a polyglucosamine PGB-2. The LC-MS analysis was conducted after protein separation on the 1D-PAGE to accomplish the purpose of this study. 280 proteins were totally identified and 188 proteins were separated as acetate-related proteins in BL-4. Acetate was converted to acetyl-CoA by acetyl-CoA synthetase up-regulated in the acetate medium. The glyoxylate bypass in the acetate medium was up-regulated with over-expression of isocitrate lyases and 2D-PAGE confirmed this differential expression. Using 1H-NMR analysis, the product of isocitrate lyases, succinate, increased about 15 times in the acetate medium. During acetate metabolism proteins involved in the lipid metabolism and hexosamine biosynthesis were over-expressed in the acetate medium, while proteins involved in TCA cycle, pentose phosphate cycle and purine metabolism were down-regulated. Taken together, the results from the proteomic analysis can be applied to improve GlcN production and to develop metabolic engineering in BL-4. PMID:22211106

  18. Stability and solubility enhancement of ellagic acid in cellulose ester solid dispersions.

    PubMed

    Li, Bin; Harich, Kim; Wegiel, Lindsay; Taylor, Lynne S; Edgar, Kevin J

    2013-02-15

    Structurally varied, carboxyl-containing cellulose derivatives were evaluated for their ability to form amorphous solid dispersions (ASD) with ellagic acid (EA), in order to improve the solubility of this high-melting, poorly bioavailable, but highly bioactive natural flavonoid compound. ASDs of EA with carboxymethylcellulose acetate butyrate (CMCAB), cellulose acetate adipate propionate (CAAdP), and hydroxypropylmethylcellulose acetate succinate (HPMCAS) were prepared, and EA dissolution from these ASDs was compared with that from pure crystalline EA and from EA/poly(vinylpyrrolidinone) (PVP) solid dispersions (SD). Polymer/drug mixtures were characterized by powder X-ray diffraction (XRPD), modulated differential scanning calorimetry (MDSC), nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FT-IR). The XRPD and FT-IR results indicated that EA was amorphous in solid dispersions with EA concentration up to 25 wt%. The stability against crystallization and solution concentrations of EA from these solid dispersions were significantly higher than those observed for physical mixtures and pure crystalline EA. HPMCAS stabilized EA most effectively, among the polymers tested, against both chemical degradation and recrystallization. The relative ability to solubilize EA from ASDs at pH 6.8 was PVP>HPMCAS>CMCAB. EA dissolves from ASD in PVP quickly and completely (maximum 92%) at pH 6.8, but EA is also released from PVP at pH 1.2, and then crystallizes rapidly. Therefore PVP is not a practical candidate for EA ASD. In contrast, the cellulose derivative ASDs show very slow EA release at pH 1.2 (<4%) and faster but still incomplete drug release at pH 6.8 (maximum 35% for HPMCAS SD). The pH-triggered drug release from HPMCAS ASD makes HPMCAS a practical choice for EA solubility enhancement. PMID:23399175

  19. Purification process for succinic acid produced by fermentation

    SciTech Connect

    Glassner, D.A.; Elankovan, P.; Beacom, D.R.

    1995-12-31

    Succinic acid is a versatile four-carbon dicarboxylic acid. It can be used commercially as an intermediate chemical for the manufacture of 1,4-butanediol, maleic anhydride, and many other chemicals. Succinic acid can be produced by the fermentation of carbohydrates. A complete process for the production and purification of succinic acid from carbohydrates has been developed. The process includes fermentation, desalting electrodialysis, water-splitting electrodialysis, and crystallization to produce a pure crystalline succinic acid. This article will present experimental work performed in the development of this process.

  20. [The application of succine in sports].

    PubMed

    S V, Okovityi; S V, Rad'Ko

    2015-01-01

    The development of energy deficiency in the course of physical exercises that eventually leads to serious derangement of the energy metabolism is an important component of the deterioration of physical and intellectual working capacity. The most promising approach to the correction of impaired physical and intellectual working capacity associated with energy deficiency consists in the application of pharmaceutical preparations containing intermediate products of the tricarbonic acid cycle. Of great promise in this context is succinic acid by virtue of its oxidation in endogenous reactions that constitutes the physiological adaptive mechanism by which resistance of the organism to oxygen deficiency is promoted. PMID:26841533

  1. Structure Determination and Characterization of the Vitamin B[superscript 6] Degradative Enzyme (E)-2-(Acetamidomethylene)succinate Hydrolase

    SciTech Connect

    McCulloch, Kathryn M.; Mukherjee, Tathagata; Begley, Tadhg P.; Ealick, Steven E.

    2010-06-22

    The gene identification and kinetic characterization of (E)-2-(acetamidomethylene)succinate (E-2AMS) hydrolase has recently been described. This enzyme catalyzes the final reaction in the degradation of vitamin B{sub 6} and produces succinic semialdehyde, acetate, ammonia, and carbon dioxide from E-2AMS. The structure of E-2AMS hydrolase was determined to 2.3 {angstrom} using SAD phasing. E-2AMS hydrolase is a member of the {alpha}/{beta} hydrolase superfamily and utilizes a serine/histidine/aspartic acid catalytic triad. Mutation of either the nucleophilic serine or the aspartate resulted in inactive enzyme. Mutation of an additional serine residue in the active site causes the enzyme to be unstable and is likely structurally important. The structure also provides insight into the mechanism of hydrolysis of E-2AMS and identifies several potential catalytically important residues.

  2. Materials and methods for efficient succinate and malate production

    DOEpatents

    Jantama, Kaemwich; Haupt, Mark John; Zhang, Xueli; Moore, Jonathan C; Shanmugam, Keelnatham T; Ingram, Lonnie O'Neal

    2014-04-08

    Genetically engineered microorganisms have been constructed to produce succinate and malate in mineral salt media in pH-controlled batch fermentations without the addition of plasmids or foreign genes. The subject invention also provides methods of producing succinate and malate comprising the culture of genetically modified microorganisms.

  3. 21 CFR 520.784 - Doxylamine succinate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.784 Doxylamine succinate tablets. (a) Specifications. The drug...

  4. 21 CFR 522.784 - Doxylamine succinate injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Doxylamine succinate injection. 522.784 Section 522.784 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.784 Doxylamine succinate injection....

  5. Inhibition of mitochondrial aconitase by succination in fumarate hydratase deficiency.

    PubMed

    Ternette, Nicola; Yang, Ming; Laroyia, Mahima; Kitagawa, Mitsuhiro; O'Flaherty, Linda; Wolhulter, Kathryn; Igarashi, Kaori; Saito, Kaori; Kato, Keiko; Fischer, Roman; Berquand, Alexandre; Kessler, Benedikt M; Lappin, Terry; Frizzell, Norma; Soga, Tomoyoshi; Adam, Julie; Pollard, Patrick J

    2013-03-28

    The gene encoding the Krebs cycle enzyme fumarate hydratase (FH) is mutated in hereditary leiomyomatosis and renal cell cancer (HLRCC). Loss of FH activity causes accumulation of intracellular fumarate, which can directly modify cysteine residues to form 2-succinocysteine through succination. We undertook a proteomic-based screen in cells and renal cysts from Fh1 (murine FH)-deficient mice and identified 94 protein succination targets. Notably, we identified the succination of three cysteine residues in mitochondrial Aconitase2 (ACO2) crucial for iron-sulfur cluster binding. We show that fumarate exerts a dose-dependent inhibition of ACO2 activity, which correlates with increased succination as determined by mass spectrometry, possibly by interfering with iron chelation. Importantly, we show that aconitase activity is impaired in FH-deficient cells. Our data provide evidence that succination, resulting from FH deficiency, targets and potentially alters the function of multiple proteins and may contribute to the dysregulated metabolism observed in HLRCC. PMID:23499446

  6. Synthesis, crystal growth and characterization of an organic material: 2-Aminopyridinium succinate succinic acid single crystal.

    PubMed

    Magesh, M; Bhagavannarayana, G; Ramasamy, P

    2015-11-01

    The 2-aminopyridinium succinate succinic acid (2APS) single crystal was synthesized and grown by slow evaporation method. The crystal structure has been confirmed by powder X-ray diffraction as well as single crystal X-ray diffraction analysis. The crystal perfection has been evaluated by high resolution X-ray diffraction (HRXRD). The grown crystal is transparent in the visible and near infrared region. The optical absorption edge was found to be 348 nm. The fluorescence study was carried out by spectrofluorophotometer. The thermal stability of grown crystal was analyzed by thermal gravimetric and differential thermal gravimetric (TG-DTA) analysis. Vicker's hardness study carried out at room temperature shows increased hardness while increasing the load. Laser damage threshold value was determined by Nd:YAG laser operating at 1064 nm. The grown 2APS crystal was characterized by etching studies using water as etchant. PMID:26099828

  7. Investigation of drug-excipient interactions in lapatinib amorphous solid dispersions using solid-state NMR spectroscopy.

    PubMed

    Song, Yang; Yang, Xinghao; Chen, Xin; Nie, Haichen; Byrn, Stephen; Lubach, Joseph W

    2015-03-01

    This study investigated the presence of specific drug-excipient interactions in amorphous solid dispersions of lapatinib (LB) and four commonly used pharmaceutical polymers, including Soluplus, polyvinylpyrrolidone vinyl acetate (PVPVA), hydroxypropylmethylcellulose acetate succinate (HPMCAS), and hydroxypropylmethylcellulose phthalate (HPMCP). Based on predicted pKa differences, LB was hypothesized to exhibit a specific ionic interaction with HPMCP, and possibly with HPMCAS, while Soluplus and PVPVA were studied as controls without ionizable functionality. Thermal studies showed a single glass transition (Tg) for each dispersion, in close agreement with predicted values for Soluplus, PVPVA, and HPMCAS systems. However, the Tg values of LB-HPMCP solid dispersions were markedly higher than predicted values, indicating a strong intermolecular interaction between LB and HPMCP. (15)N solid-state NMR provided direct spectroscopic evidence for protonation of LB (i.e., salt formation) within the HPMCP solid dispersions. (1)H T1 and (1)H T1ρ relaxation studies of the dispersions supported the ionic interaction hypothesis, and indicated multiple phases in the cases of excess drug or polymer. In addition, the dissolution and stability behavior of each system was examined. Both acidic polymers, HPMCAS and HPMCP, effectively inhibited the crystallization of LB on accelerated stability, likely owing to beneficial strong intermolecular hydrogen and/or specific ionic bonds with the acidic polymers. Soluplus and PVPVA showed poor physical properties on stability and subsequently poor crystallization inhibition. PMID:25585133

  8. Method to produce succinic acid from raw hydrolysates

    DOEpatents

    Donnelly, Mark I.; Sanville-Millard, Cynthia Y.; Nghiem, Nhuan Phu

    2004-06-01

    A method for producing succinic acid from industrial-grade hydrolysates is provided, comprising supplying an organism that contains mutations for the genes ptsG, pflB, and ldhA, allowing said organism to accumulate biomass, and allowing said organism to metabolize the hydrolysate. Also provided is a bacteria mutant characterized in that it produces succinic acid from substrate contained in industrial-grade hydrolysate in a ratio of between 0.6:1 and 1.3:1 succinic acid to substrate.

  9. Acute pancreatitis and acute renal failure complicating doxylamine succinate intoxication.

    PubMed

    Lee, Yang Deok; Lee, Soo Teik

    2002-06-01

    Doxylamine succinate is an antihistaminic drugwith additional hypnotic, anticholinergic and local anesthetic effects first described in 1948. In Korea and many other countries, it is a common-over-the counter medication frequently involved in overdoses. Clinical symtomatology of doxylamine succinate overdose includes somnolence, coma, seizures, mydriasis, tachycardia, psychosis, and rhabdomyolysis. A serious complication may be rhabdomyolysis with subsequent impairment of renal function and acute renal failure. We report a case of acute renal failure and acute pancreatitis complicating a doxylamine succinate intoxication. PMID:12046971

  10. Ercella succinigenes gen. nov., sp. nov., an anaerobic succinate-producing bacterium.

    PubMed

    van Gelder, Antonie H; Sousa, Diana Z; Rijpstra, W Irene C; Damsté, Jaap S Sinninghe; Stams, Alfons J M; Sánchez-Andrea, Irene

    2014-07-01

    A novel anaerobic succinate-producing bacterium, strain ZWB(T), was isolated from sludge collected from a biogas desulfurization bioreactor (Eerbeek, the Netherlands). Cells were non-spore-forming, motile, slightly curved rods (0.4-0.5 µm in diameter and 2-3 µm in length), and stained Gram-negative. The temperature range for growth was 25-40 °C, with an optimum at 37 °C. The pH range for growth was 7.0-9.0, with an optimum at pH 7.5. Strain ZWB(T) was able to ferment glycerol and several carbohydrates mainly to H2, succinate and acetate. Sulfur and fumarate could be used as electron acceptors by strain ZWB(T). The G+C content of the genomic DNA was 37.6 mol%. The most abundant fatty acids were iso-C14 : 0 and iso-C16 : 0 DMA. On the basis of 16S rRNA gene sequence similarity, strain ZWB(T) belongs to the family Ruminococcaceae and it is distantly related to Saccharofermentans acetigenes JCM 14006(T) (92.1%). Based on the physiological features and phylogenetic analysis, strain ZWB(T) represents a novel species of a new genus, for which the name Ercella succinigenes gen. nov., sp. nov. is proposed. The type strain of Ercella succinigenes is ZWB(T) ( = DSM 27333(T) = JCM 19283(T)). PMID:24776531

  11. Carbon flux analysis by 13C nuclear magnetic resonance to determine the effect of CO2 on anaerobic succinate production by Corynebacterium glutamicum.

    PubMed

    Radoš, Dušica; Turner, David L; Fonseca, Luís L; Carvalho, Ana Lúcia; Blombach, Bastian; Eikmanns, Bernhard J; Neves, Ana Rute; Santos, Helena

    2014-05-01

    Wild-type Corynebacterium glutamicum produces a mixture of lactic, succinic, and acetic acids from glucose under oxygen deprivation. We investigated the effect of CO2 on the production of organic acids in a two-stage process: cells were grown aerobically in glucose, and subsequently, organic acid production by nongrowing cells was studied under anaerobic conditions. The presence of CO2 caused up to a 3-fold increase in the succinate yield (1 mol per mol of glucose) and about 2-fold increase in acetate, both at the expense of l-lactate production; moreover, dihydroxyacetone formation was abolished. The redistribution of carbon fluxes in response to CO2 was estimated by using (13)C-labeled glucose and (13)C nuclear magnetic resonance (NMR) analysis of the labeling patterns in end products. The flux analysis showed that 97% of succinate was produced via the reductive part of the tricarboxylic acid cycle, with the low activity of the oxidative branch being sufficient to provide the reducing equivalents needed for the redox balance. The flux via the pentose phosphate pathway was low (~5%) regardless of the presence or absence of CO2. Moreover, there was significant channeling of carbon to storage compounds (glycogen and trehalose) and concomitant catabolism of these reserves. The intracellular and extracellular pools of lactate and succinate were measured by in vivo NMR, and the stoichiometry (H(+):organic acid) of the respective exporters was calculated. This study shows that it is feasible to take advantage of natural cellular regulation mechanisms to obtain high yields of succinate with C. glutamicum without genetic manipulation. PMID:24610842

  12. Carbon Flux Analysis by 13C Nuclear Magnetic Resonance To Determine the Effect of CO2 on Anaerobic Succinate Production by Corynebacterium glutamicum

    PubMed Central

    Radoš, Dušica; Turner, David L.; Fonseca, Luís L.; Carvalho, Ana Lúcia; Blombach, Bastian; Eikmanns, Bernhard J.; Neves, Ana Rute

    2014-01-01

    Wild-type Corynebacterium glutamicum produces a mixture of lactic, succinic, and acetic acids from glucose under oxygen deprivation. We investigated the effect of CO2 on the production of organic acids in a two-stage process: cells were grown aerobically in glucose, and subsequently, organic acid production by nongrowing cells was studied under anaerobic conditions. The presence of CO2 caused up to a 3-fold increase in the succinate yield (1 mol per mol of glucose) and about 2-fold increase in acetate, both at the expense of l-lactate production; moreover, dihydroxyacetone formation was abolished. The redistribution of carbon fluxes in response to CO2 was estimated by using 13C-labeled glucose and 13C nuclear magnetic resonance (NMR) analysis of the labeling patterns in end products. The flux analysis showed that 97% of succinate was produced via the reductive part of the tricarboxylic acid cycle, with the low activity of the oxidative branch being sufficient to provide the reducing equivalents needed for the redox balance. The flux via the pentose phosphate pathway was low (∼5%) regardless of the presence or absence of CO2. Moreover, there was significant channeling of carbon to storage compounds (glycogen and trehalose) and concomitant catabolism of these reserves. The intracellular and extracellular pools of lactate and succinate were measured by in vivo NMR, and the stoichiometry (H+:organic acid) of the respective exporters was calculated. This study shows that it is feasible to take advantage of natural cellular regulation mechanisms to obtain high yields of succinate with C. glutamicum without genetic manipulation. PMID:24610842

  13. Novel membrane-based biotechnological alternative process for succinic acid production and chemical synthesis of bio-based poly (butylene succinate).

    PubMed

    Wang, Caixia; Ming, Wei; Yan, Daojiang; Zhang, Congcong; Yang, Maohua; Liu, Yilan; Zhang, Yu; Guo, Baohua; Wan, Yinhua; Xing, Jianmin

    2014-03-01

    Succinic acid was produced in a novel membrane-based fermentation and separation integrated system. With this integrated system, product inhibition was alleviated by removing acids and replenishing fresh broth. High cell density maintain for a longer time from 75 to 130h and succinic acid concentration increased from 53 to 73g/L. In the developed separation process, succinic acid was crystallized at a recovery of 85-90%. The purity of the obtained succinic acid crystals reached 99.4% as found by HPLC and (1)H NMR analysis. A crystallization experiment indicated that among by-products glucose had a negative effect on succinic acid crystallization. Poly (butylene succinate) (PBS) was synthesized using the purified succinic acid and (1)H NMR analysis confirmed that the composition of the synthesized PBS is in agreement with that from petro-based succinic acid. PMID:24472699

  14. Succinate Dehydrogenase Loss in Familial Paraganglioma: Biochemistry, Genetics, and Epigenetics

    PubMed Central

    Her, Yeng F.; Maher, L. James

    2015-01-01

    It is counterintuitive that metabolic defects reducing ATP production can cause, rather than protect from, cancer. Yet this is precisely the case for familial paraganglioma, a form of neuroendocrine malignancy caused by loss of succinate dehydrogenase in the tricarboxylic acid cycle. Here we review biochemical, genetic, and epigenetic considerations in succinate dehydrogenase loss and present leading models and mysteries associated with this fascinating and important tumor. PMID:26294907

  15. Biologically produced succinic acid: A new route to chemical intermediates

    SciTech Connect

    1995-09-01

    The national laboratory consortium has undertaken an R&D project with the Michigan Biotechnology Institute (MBI) to demonstrate the feasibility of producing a chemical intermediate, succinic acid, and various derivatives, from renewable agricultural resources. The projects near-term goal is to demonstrate an economically competetive process for producing 1,4-butanediol and other derivatives from biologically produced succinic acid without generating a major salt waste. The competitiveness to the petrochemical process must be demonstrated.

  16. Economical succinic acid production from cane molasses by Actinobacillus succinogenes.

    PubMed

    Liu, Yu-Peng; Zheng, Pu; Sun, Zhi-Hao; Ni, Ye; Dong, Jin-Jun; Zhu, Lei-Lei

    2008-04-01

    In this work, production of succinic acid by Actinobacillus succinogenes CGMCC1593 using cane molasses as a low cost carbon source was developed. In anaerobic bottles fermentation, succinic acid concentration of 50.6+/-0.9 g l(-1) was attained at 60 h using an optimum medium containing molasses pretreated with sulfuric acid, resulting in a succinic acid yield of 79.5+/-1.1% and sugar utilization of 97.1+/-0.6%. When batch fermentation was carried out in a 5-l stirred bioreactor with pretreated molasses, 46.4 g l(-1) of succinic acid was attained at 48 h and faster cells growth was also observed. Fed batch fermentation was performed to minimize the substrate (sugar) inhibition effect, giving 55.2 g l(-1) of succinic acid and 1.15 g l(-1)h(-1) of productivity at 48 h. The present study suggests that the inexpensive cane molasses could be utilized for the economical and efficient production of succinic acid by A. succinogenes. PMID:17532626

  17. Formulation development of metoprolol succinate and hydrochlorothiazide compression coated tablets.

    PubMed

    Shah, Ritesh; Parmar, Swatil; Patel, Hetal; Pandey, Sonia; Shah, Dinesh

    2013-12-01

    The purpose of present research work was to design and optimize compression coated tablet to provide an immediate release of hydrochlorothiazide in stomach and extended release of metoprolol succinate in intestine. Compression coated tablet was prepared by direct compression method which consisted of metoprolol succinate extended release core tablet and hydrochlorothiazide immediate release coat layer. Barrier coating of Hydroxy Propyl Methyl Cellulose (HPMC) E15LV was applied onto the core tablets to prevent burst release of metoprolol succinate in acidic medium. A 32 full factorial design was employed for optimization of the amount of polymers required to achieve extended release of drug. The percentage drug release at given time Q3, Q6, Q10, Q22; were selected as dependent variables. Core and compression coated tablets were evaluated for pharmaco-technical parameters. In vitro drug release of optimized batch was found to comply with Pharmacopoeial specifications. Desired release of metoprolol succinate was obtained by suitable combination of HPMC having high gelling capacity and polyethylene oxide having quick gelling capacity. The mechanism of release of metoprolol succinate from all batches was anomalous diffusion. Optimised batch was stable at accelerated conditions up to 3 months. Thus, compression coated tablet of metoprolol succinate and hydrochlorothiazide was successfully formulated. PMID:23017092

  18. The Succinated Proteome of FH-Mutant Tumours.

    PubMed

    Yang, Ming; Ternette, Nicola; Su, Huizhong; Dabiri, Raliat; Kessler, Benedikt M; Adam, Julie; Teh, Bin Tean; Pollard, Patrick J

    2014-01-01

    Inherited mutations in the Krebs cycle enzyme fumarate hydratase (FH) predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC). Loss of FH activity in HLRCC tumours causes accumulation of the Krebs cycle intermediate fumarate to high levels, which may act as an oncometabolite through various, but not necessarily mutually exclusive, mechanisms. One such mechanism, succination, is an irreversible non-enzymatic modification of cysteine residues by fumarate, to form S-(2-succino)cysteine (2SC). Previous studies have demonstrated that succination of proteins including glyceraldehyde 3-phosphate dehydrogenase (GAPDH), kelch-like ECH-associated protein 1 (KEAP1) and mitochondrial aconitase (ACO2) can have profound effects on cellular metabolism. Furthermore, immunostaining for 2SC is a sensitive and specific biomarker for HLRCC tumours. Here, we performed a proteomic screen on an FH-mutant tumour and two HLRCC-derived cancer cell lines and identified 60 proteins where one or more cysteine residues were succinated; 10 of which were succinated at cysteine residues either predicted, or experimentally proven, to be functionally significant. Bioinformatic enrichment analyses identified most succinated targets to be involved in redox signaling. To our knowledge, this is the first proteomic-based succination screen performed in human tumours and cancer-derived cells and has identified novel 2SC targets that may be relevant to the pathogenesis of HLRCC. PMID:25105836

  19. The Succinated Proteome of FH-Mutant Tumours

    PubMed Central

    Yang, Ming; Ternette, Nicola; Su, Huizhong; Dabiri, Raliat; Kessler, Benedikt M.; Adam, Julie; Teh, Bin Tean; Pollard, Patrick J.

    2014-01-01

    Inherited mutations in the Krebs cycle enzyme fumarate hydratase (FH) predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC). Loss of FH activity in HLRCC tumours causes accumulation of the Krebs cycle intermediate fumarate to high levels, which may act as an oncometabolite through various, but not necessarily mutually exclusive, mechanisms. One such mechanism, succination, is an irreversible non-enzymatic modification of cysteine residues by fumarate, to form S-(2-succino)cysteine (2SC). Previous studies have demonstrated that succination of proteins including glyceraldehyde 3-phosphate dehydrogenase (GAPDH), kelch-like ECH-associated protein 1 (KEAP1) and mitochondrial aconitase (ACO2) can have profound effects on cellular metabolism. Furthermore, immunostaining for 2SC is a sensitive and specific biomarker for HLRCC tumours. Here, we performed a proteomic screen on an FH-mutant tumour and two HLRCC-derived cancer cell lines and identified 60 proteins where one or more cysteine residues were succinated; 10 of which were succinated at cysteine residues either predicted, or experimentally proven, to be functionally significant. Bioinformatic enrichment analyses identified most succinated targets to be involved in redox signaling. To our knowledge, this is the first proteomic-based succination screen performed in human tumours and cancer-derived cells and has identified novel 2SC targets that may be relevant to the pathogenesis of HLRCC. PMID:25105836

  20. Towards hyperpolarized 13C-succinate imaging of brain cancer

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Pratip; Chekmenev, Eduard Y.; Perman, William H.; Harris, Kent C.; Lin, Alexander P.; Norton, Valerie A.; Tan, Chou T.; Ross, Brian D.; Weitekamp, Daniel P.

    2007-05-01

    We describe a novel 13C enriched precursor molecule, sodium 1- 13C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized 13C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized 13C sodium succinate, contained significant concentrations of the injected substrate, 13C sodium succinate, together with 13C maleate and succinate metabolites 1- 13C-glutamate, 5- 13C-glutamate, 1- 13C-glutamine and 5- 13C-glutamine. The 13C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized 13C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images.

  1. Preparation of vinyl acetate

    DOEpatents

    Tustin, Gerald Charles; Zoeller, Joseph Robert; Depew, Leslie Sharon

    1998-01-01

    This invention pertains to the preparation of vinyl acetate by contacting a mixture of hydrogen and ketene with a heterogeneous catalyst containing a transition metal to produce acetaldehyde, which is then reacted with ketene in the presence of an acid catalyst to produce vinyl acetate.

  2. Preparation of vinyl acetate

    DOEpatents

    Tustin, G.C.; Zoeller, J.R.; Depew, L.S.

    1998-03-24

    This invention pertains to the preparation of vinyl acetate by contacting a mixture of hydrogen and ketene with a heterogeneous catalyst containing a transition metal to produce acetaldehyde, which is then reacted with ketene in the presence of an acid catalyst to produce vinyl acetate.

  3. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS.

    PubMed

    Chouchani, Edward T; Pell, Victoria R; Gaude, Edoardo; Aksentijević, Dunja; Sundier, Stephanie Y; Robb, Ellen L; Logan, Angela; Nadtochiy, Sergiy M; Ord, Emily N J; Smith, Anthony C; Eyassu, Filmon; Shirley, Rachel; Hu, Chou-Hui; Dare, Anna J; James, Andrew M; Rogatti, Sebastian; Hartley, Richard C; Eaton, Simon; Costa, Ana S H; Brookes, Paul S; Davidson, Sean M; Duchen, Michael R; Saeb-Parsy, Kourosh; Shattock, Michael J; Robinson, Alan J; Work, Lorraine M; Frezza, Christian; Krieg, Thomas; Murphy, Michael P

    2014-11-20

    Ischaemia-reperfusion injury occurs when the blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death and aberrant immune responses through the generation of mitochondrial reactive oxygen species (ROS). Although mitochondrial ROS production in ischaemia reperfusion is established, it has generally been considered a nonspecific response to reperfusion. Here we develop a comparative in vivo metabolomic analysis, and unexpectedly identify widely conserved metabolic pathways responsible for mitochondrial ROS production during ischaemia reperfusion. We show that selective accumulation of the citric acid cycle intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase, which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. After reperfusion, the accumulated succinate is rapidly re-oxidized by succinate dehydrogenase, driving extensive ROS generation by reverse electron transport at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo ischaemia-reperfusion injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of ischaemia-reperfusion injury. Furthermore, these findings reveal a new pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation after subsequent reperfusion is a potential therapeutic target to decrease ischaemia

  4. Succinate dehydrogenase gene mutations in cardiac paragangliomas.

    PubMed

    Martucci, Victoria L; Emaminia, Abbas; del Rivero, Jaydira; Lechan, Ronald M; Magoon, Bindiya T; Galia, Analyza; Fojo, Tito; Leung, Steve; Lorusso, Roberto; Jimenez, Camilo; Shulkin, Barry L; Audibert, Jennifer L; Adams, Karen T; Rosing, Douglas R; Vaidya, Anand; Dluhy, Robert G; Horvath, Keith A; Pacak, Karel

    2015-06-15

    Pheochromocytomas and paragangliomas are chromaffin cell tumors arising from neuroendocrine cells. At least 1/3 of paragangliomas are related to germline mutations in 1 of 17 genes. Although these tumors can occur throughout the body, cardiac paragangliomas are very rare, accounting for <0.3% of mediastinal tumors. The purpose of this study was to determine the clinical characteristics of patients with cardiac paragangliomas, particularly focusing on their genetic backgrounds. A retrospective chart analysis of 15 patients with cardiac paragangliomas was performed to determine clinical presentation, genetic background, diagnostic workup, and outcomes. The average age at diagnosis was 41.9 years. Typical symptoms of paraganglioma (e.g., hypertension, sweating, palpitations, headache) were reported at initial presentation in 13 patients (86.7%); the remaining 2, as well as 4 symptomatic patients, initially presented with cardiac-specific symptoms (e.g., chest pain, dyspnea). Genetic testing was done in 13 patients (86.7%); 10 (76.9%) were positive for mutations in succinate dehydrogenase (SDHx) subunits B, C, or D. Thirteen patients (86.7%) underwent surgery to remove the paraganglioma with no intraoperative morbidity or mortality; 1 additional patient underwent surgical resection but experienced intraoperative complications after removal of the tumor due to co-morbidities and did not survive. SDHx mutations are known to be associated with mediastinal locations and malignant behavior of paragangliomas. In this report, the investigators extend the locations of predominantly SDHx-related paragangliomas to cardiac tumors. In conclusion, cardiac paragangliomas are frequently associated with underlying SDHx germline mutations, suggesting a need for genetic testing of all patients with this rare tumor. PMID:25896150

  5. Characterization of nanoscale spatial distribution of small molecules in amorphous polymer matrices

    NASA Astrophysics Data System (ADS)

    Ricarte, Ralm; Hillmyer, Marc; Lodge, Timothy

    Hydroxypropyl methylcellulose acetate succinate (HPMCAS) can significantly enhance the efficacy of active pharmaceutical ingredients (APIs). Yet, the interactions between species in HPMCAS-API blends are not understood. Elucidating these interactions is difficult because the spatial distributions of HPMCAS and API in the blends are ambiguous; the polymer and drug may be molecularly mixed or the species may form phase separated domains. As these phase separated domains may be less than 100 nm in size, traditional characterization techniques may not accurately evaluate the spatial distribution. To address this challenge, we explore the use of electron energy-loss spectroscopy (EELS) for detecting the model API phenytoin in an HPMCAS-phenytoin blend. Using EELS, we directly measured with high accuracy and precision the phenytoin concentrations in several blends. We present evidence that suggests phase separation occurs in blends that have a phenytoin loading of approximately 50 wt percent. Finally, we demonstrate that this technique achieves a sub-100 nm spatial resolution and can detect several other APIs.

  6. In vivo bioavailability studies of sumatriptan succinate buccal tablets

    PubMed Central

    Shivanand, K; Raju, SA; Nizamuddin, S; Jayakar, B

    2011-01-01

    Back ground and the purpose of study Sumatriptan succinate is a Serotonin 5- HT1 receptor agonist, used in treatment of migraine. It is absorbed rapidly but incompletely when given orally and undergoes first-pass metabolism, resulting in a low absolute bioavailability of about 15%. The aim of this work was to design mucoadhesive bilayered buccal tablets of sumatriptan succinate to improve its bioavailability. Methods Mucoadhesive polymers carbopol 934 (Carbopol), HPMC K4M, HPMC K15M along with ethyl cellulose as an impermeable backing layer were used for the preparation of mucoadhesive bilayered tablets. In vivo bioavailability studies was also conducted in rabbits for optimized formulation using oral solution of sumatriptan succinate as standard. Results Bilayered buccal tablets (BBT) containing the mixture of Carbopol and HPMC K4M in the ratio 1:1 (T1) had the maximum percentage of in vitro drug release within 6 hrs. The optimized formulation (T1) followed non-Fickian release mechanism. The percentage relative bioavailability of sumatriptan succinate from selected bilayered buccal tablets (T1) was found to be 140.78%. Conclusions Bilayered buccal tablets of sumatriptan succinate was successfully prepared with improved bioavailability. PMID:22615661

  7. Recent advances in production of succinic acid from lignocellulosic biomass.

    PubMed

    Akhtar, Junaid; Idris, Ani; Abd Aziz, Ramlan

    2014-02-01

    Production of succinic acid via separate enzymatic hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF) are alternatives and are environmentally friendly processes. These processes have attained considerable positions in the industry with their own share of challenges and problems. The high-value succinic acid is extensively used in chemical, food, pharmaceutical, leather and textile industries and can be efficiently produced via several methods. Previously, succinic acid production via chemical synthesis from petrochemical or refined sugar has been the focus of interest of most reviewers. However, these expensive substrates have been recently replaced by alternative sustainable raw materials such as lignocellulosic biomass, which is cheap and abundantly available. Thus, this review focuses on succinic acid production utilizing lignocellulosic material as a potential substrate for SSF and SHF. SSF is an economical single-step process which can be a substitute for SHF - a two-step process where biomass is hydrolyzed in the first step and fermented in the second step. SSF of lignocellulosic biomass under optimum temperature and pH conditions results in the controlled release of sugar and simultaneous conversion into succinic acid by specific microorganisms, reducing reaction time and costs and increasing productivity. In addition, main process parameters which influence SHF and SSF processes such as batch and fed-batch fermentation conditions using different microbial strains are discussed in detail. PMID:24292125

  8. Succinate esters: odd-even effects in melting points.

    PubMed

    Joseph, Sumy; Sathishkumar, Ranganathan

    2014-10-01

    Dialkyl succinates show a pattern of alternating behavior in their melting points, as the number of C atoms in the alkane side chain increases, unlike in the dialkyl oxalates [Joseph et al. (2011). Acta Cryst. B67, 525-534]. Dialkyl succinates with odd numbers of C atoms in the alkyl side chain show higher melting points than the immediately adjacent analogues with even numbers. The crystal structures and their molecular packing have been analyzed for a series of dialkyl succinates with 1-4 C atoms in the alkyl side chain. The energy difference (ΔE) between the optimized and observed molecular conformations, density, Kitaigorodskii packing index (KPI) and C-H...O interactions are considered to rationalize this behavior. In contrast to the dialkyl oxalates where a larger number of moderately strong C-H...O interactions were characteristic of oxalates with elevated melting points, here the molecular packing and the density play a major role in raising the melting point. On moving from oxalate to succinate esters the introduction of the C2 spacer adds two activated H atoms to the asymmetric unit, resulting in the formation of stronger C-H...O hydrogen bonds in all succinates. As a result the crystallinity of long-chain alkyl substituted esters improves enormously in the presence of hydrogen bonds from activated donors. PMID:25274517

  9. Antioxidant and antitumor activity of trolox, trolox succinate, and α-tocopheryl succinate conjugates with nitroxides.

    PubMed

    Zakharova, Ol'ga D; Frolova, Tat'yana S; Yushkova, Yuliya V; Chernyak, Elena I; Pokrovsky, Andrei G; Pokrovsky, Mikhail A; Morozov, Sergei V; Sinitsina, Ol'ga I; Grigor'ev, Igor A; Nevinsky, Georgy A

    2016-10-21

    A possible ability of twelve new derivatives of known antioxidants trolox (TroH), trolox succinate (TroS), α-tocopheryl succinate (α-TOS) containing nitroxyl radicals (1-12) to protect bacterial cells from spontaneous and peroxide-induced mutagenesis and their cytotoxicity against six different tumor cells as well as two normal cells were investigated and compared with that for TroH, TroS, α-TOH, and α-TOS for the first time. In contrast to TroH and TroS, all nitroxide derivatives 1-12 demonstrated not only antioxidant properties, but also suppress the growth of human tumor cells: myeloma, mammary adenocarcinoma, hepatocarcinoma, T cells leukemia, histiocytic lymphoma, and T-cellular leucosis. The IC50 values (24 - ≥ 300 μM) depend significantly on the compounds and type of tumor cells. Some compounds were capable to inhibit the growth of normal mouse (LMTK) and hamster (AG17) fibroblast cells and demonstrate very different ratios in inhibition of various tumor and normal cell lines. Some nitroxide conjugates showed pronounced selectivity in suppressing the growth of several cancer cells. Overall, several compounds may be promising in parallel as antioxidants and as specific inhibitors of some tumor cells growth. Among considered spin labeled conjugates the most perspective derivatives as antioxidants and as antitumor agents are the compounds containing pyrrolidine nitroxides. In contrast to spin labeled TroH, TroS and α-TOS conjugates 1-12 succinyl derivatives 13-15 were inactive in inhibiting the growth of any tumor cells. It means that for suppressing the cancer cells the compounds should contain in their structures fragments of TroH, TroS or α-TOS. PMID:27344490

  10. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS

    PubMed Central

    Gaude, Edoardo; Aksentijević, Dunja; Sundier, Stephanie Y.; Robb, Ellen L.; Logan, Angela; Nadtochiy, Sergiy M.; Ord, Emily N. J.; Smith, Anthony C.; Eyassu, Filmon; Shirley, Rachel; Hu, Chou-Hui; Dare, Anna J.; James, Andrew M.; Rogatti, Sebastian; Hartley, Richard C.; Eaton, Simon; Costa, Ana S.H.; Brookes, Paul S.; Davidson, Sean M.; Duchen, Michael R.; Saeb-Parsy, Kourosh; Shattock, Michael J.; Robinson, Alan J.; Work, Lorraine M.; Frezza, Christian; Krieg, Thomas; Murphy, Michael P.

    2014-01-01

    Ischaemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death, and aberrant immune responses through generation of mitochondrial reactive oxygen species (ROS)1-5. Although mitochondrial ROS production in IR is established, it has generally been considered a non-specific response to reperfusion1,3. Here, we developed a comparative in vivo metabolomic analysis and unexpectedly identified widely conserved metabolic pathways responsible for mitochondrial ROS production during IR. We showed that selective accumulation of the citric acid cycle (CAC) intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase (SDH), which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. Upon reperfusion, the accumulated succinate is rapidly re-oxidised by SDH, driving extensive ROS generation by reverse electron transport (RET) at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo IR injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of IR injury. Furthermore, these findings reveal a novel pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation upon subsequent reperfusion is a potential therapeutic target to decrease IR injury in a range of pathologies. PMID:25383517

  11. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    2002-01-01

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  12. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, M.; Millard, C.S.; Stols, L.

    1998-06-23

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria. 2 figs.

  13. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    1998-01-01

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  14. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    2001-09-25

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  15. Simulating Succinate-Promoted Dissolution at Calcite {104} Steps

    NASA Astrophysics Data System (ADS)

    Mkhonto, D.; Sahai, N.

    2008-12-01

    Organic molecules of a wide range of molecular weights from small organic acids, amino-acids, acidic peptides and acidic proteins to humic and fulvic acids play a key role in modulating nucleation, crystal growth and dissolution of calcium carbonate polymorphs. In general, these acidic molecules inhibit calcite growth and, promote dissolution preferentially along specific crystallographic directions, in the process, regulating crystal shape and size, and even whether a metastable polymorph (e.g., vaterite or aragonite) is nucleated first. For example, chiral faces of calcite are selected by chiral amino-acids and the unusual {hk0} faces are expressed in the presence of amino-acids [Orme et al., 2001], and unusual heptagonal dissolution etch-pit are seen in the presence of succinate compared to the normal rhombohedral pits in water alone [Teng et al., 2006]. Thus, the presence of unusual crystal morphologies may indicate organic-mediated growth, thus serving as a biosignature. We have conducted the Molecular Dynamics (MD) simulations using the Consistent Valence Force Field (CVFF) as implemented in the FORCITE© module of the Materials Studio © software package (Accelrys, Inc. TM) to model the adsorption of succinate, a dicarboxylic acid, and charge- balancing Na+ ions on dry and hydrated steps in different directions on the {104} cleavage face of calcite [Mkhonto and Sahai, in prep.]. At the site of succinate adsorption, we find elongation of the interatomic distances (Ca-OCO3,i) between surface Ca2+ cation and the oxygen of the underlying inorganic CO32- anion the first surface layer of calcite, compared to the corresponding distances in the presence of water alone, suggesting greater ease of surface Ca2+ detachment. This result is consistent with the empirically observed increase in overall dissolution rate with succinate [Teng et al., 2006]. Furthermore, succinate adsorption lowers the step energies, which explains the appearance of steps in the unsusual [42

  16. Metabolism of /sup 14/C-labeled doxylamine succinate (Bendectin) in the rhesus monkey (Macaca mulatta)

    SciTech Connect

    Slikker, W. Jr.; Holder, C.L.; Lipe, G.W.; Korfmacher, W.A.; Thompson, H.C. Jr.; Bailey, J.R.

    1986-05-01

    The time-course of the metabolic fate of (/sup 14/C)doxylamine was determined after the p.o. administration of 13 mg/kg doxylamine succinate as Bendectin plus (/sup 14/C)doxylamine succinate to the rhesus monkey. Urine and plasma samples were analyzed by reversed-phase high performance liquid chromatography (HPLC), chemical derivatization, and mass spectrometry. The cumulative 48-hr urinary metabolic profile contained 81% of the administered radiolabeled dose and consisted of at least six radiolabeled peaks. They were peak 1: unknown polar metabolites (8% of dose); peak 2: 2-(1-phenyl-1-(2-pyridinyl)ethoxy) acetic acid, 1-(1-phenyl-1(2-pyridinyl)ethoxy) methanol, and another minor metabolite(s) (31%); peak 3: doxylamine-N-oxide (1%); peak 4a: N,N-didesmethyldoxylamine (17%); peak 4b: doxylamine (4%); and peak 5: N-desmethyldoxylamine (20%). The plasma metabolic profile was the same as the urinary profile except for the absence of doxylamine-N-oxide. The maximum plasma concentrations and elapsed time to attain these concentrations were as follows. Peak 1: 540 ng/mL, 4 hr; peak 2: 1700 ng/mL, 1 hr; peak 4a: 430 ng/mL, 4 hr; peak 4b: 930 ng/mL, 2 hr; and peak 5: 790 ng/mL, 2 hr. These data suggest that in the monkey, doxylamine metabolism follows at least four pathways: a minor pathway to the N-oxide; a minor pathway to unknown polar metabolites; a major pathway to mono- and didesmethyldoxylamine via successive N-demethylation; and a major pathway to side-chain cleavage products (peak 2) via direct side-chain oxidation and/or deamination.

  17. Detection of pharmaceutical crystals in polymer particles by transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Ricarte, Ralm; Hillmyer, Marc; Lodge, Timothy

    2015-03-01

    The use of solid dispersions, blends of an active pharmaceutical ingredient (API) and a polymer excipient, may significantly enhance the dissolution performance of a poorly water soluble drug. However, the polymer's role in inhibiting API crystallization within the solid dispersion is not well understood. One of the main challenges in elucidating this mechanism is the difficulty of detecting small amounts of API crystals (less than 5 volume percent) within the polymer matrix. In this work, we explore the use of transmission electron microscopy (TEM) to characterize the crystallinity of griseofulvin (GF) in hydroxypropyl methylcellulose acetate succinate (HPMCAS) solid dispersions. Using both real-space images and electron diffraction patterns from TEM, GF crystals in the HPMCAS matrix were unambiguously identified with nanometer resolution and with a crystal detection sensitivity superior to both wide-angle X-ray scattering and differential scanning calorimetry. TEM shows great potential for characterizing even trace API crystallinity in solid polymeric dispersions.

  18. 21 CFR 172.275 - Synthetic paraffin and succinic derivatives.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Synthetic paraffin and succinic derivatives. 172.275 Section 172.275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION...

  19. 21 CFR 172.275 - Synthetic paraffin and succinic derivatives.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Synthetic paraffin and succinic derivatives. 172.275 Section 172.275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION...

  20. 21 CFR 172.275 - Synthetic paraffin and succinic derivatives.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Synthetic paraffin and succinic derivatives. 172.275 Section 172.275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION...

  1. 21 CFR 172.275 - Synthetic paraffin and succinic derivatives.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Synthetic paraffin and succinic derivatives. 172.275 Section 172.275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION...

  2. 21 CFR 172.275 - Synthetic paraffin and succinic derivatives.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Synthetic paraffin and succinic derivatives. 172.275 Section 172.275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Coatings, Films...

  3. Succinate dehydrogenase is the regulator of respiration in Mycobacterium tuberculosis.

    PubMed

    Hartman, Travis; Weinrick, Brian; Vilchèze, Catherine; Berney, Michael; Tufariello, Joanne; Cook, Gregory M; Jacobs, William R

    2014-11-01

    In chronic infection, Mycobacterium tuberculosis bacilli are thought to enter a metabolic program that provides sufficient energy for maintenance of the protonmotive force, but is insufficient to meet the demands of cellular growth. We sought to understand this metabolic downshift genetically by targeting succinate dehydrogenase, the enzyme which couples the growth processes controlled by the TCA cycle with the energy production resulting from the electron transport chain. M. tuberculosis contains two operons which are predicted to encode succinate dehydrogenase enzymes (sdh-1 and sdh-2); we found that deletion of Sdh1 contributes to an inability to survive long term stationary phase. Stable isotope labeling and mass spectrometry revealed that Sdh1 functions as a succinate dehydrogenase during aerobic growth, and that Sdh2 is dispensable for this catalysis, but partially overlapping activities ensure that the loss of one enzyme can incompletely compensate for loss of the other. Deletion of Sdh1 disturbs the rate of respiration via the mycobacterial electron transport chain, resulting in an increased proportion of reduced electron carrier (menaquinol) which leads to increased oxygen consumption. The loss of respiratory control leads to an inability to recover from stationary phase. We propose a model in which succinate dehydrogenase is a governor of cellular respiration in the adaptation to low oxygen environments. PMID:25412183

  4. Method for construction of bacterial strains with increased succinic acid production

    DOEpatents

    Donnelly, Mark I.; Sanville-Millard, Cynthia; Chatterjee, Ranjini

    2000-01-01

    A fermentation process for producing succinic acid is provided comprising selecting a bacterial strain that does not produce succinic acid in high yield, disrupting the normal regulation of sugar metabolism of said bacterial strain, and combining the mutant bacterial strain and selected sugar in anaerobic conditions to facilitate production of succinic acid. Also provided is a method for changing low yield succinic acid producing bacteria to high yield succinic acid producing bacteria comprising selecting a bacterial strain having a phosphotransferase system and altering the phosphotransferase system so as to allow the bacterial strain to simultaneously metabolize different sugars.

  5. Succinic semialdehyde reductase Gox1801 from Gluconobacter oxydans in comparison to other succinic semialdehyde-reducing enzymes.

    PubMed

    Meyer, Maria; Schweiger, Paul; Deppenmeier, Uwe

    2015-05-01

    Gluconobacter oxydans is an industrially important bacterium that possesses many uncharacterized oxidoreductases, which might be exploited for novel biotechnological applications. In this study, gene gox1801 was homologously overexpressed in G. oxydans and it was found that the relative expression of gox1801 was 13-fold higher than that in the control strain. Gox1801 was predicted to belong to the 3-hydroxyisobutyrate dehydrogenase-type proteins. The purified enzyme had a native molecular mass of 134 kDa and forms a homotetramer. Analysis of the enzymatic activity revealed that Gox1801 is a succinic semialdehyde reductase that used NADH and NADPH as electron donors. Lower activities were observed with glyoxal, methylglyoxal, and phenylglyoxal. The enzyme was compared to the succinic semialdehyde reductase GsSSAR from Geobacter sulfurreducens and the γ-hydroxybutyrate dehydrogenase YihU from Escherichia coli K-12. The comparison revealed that Gox1801 is the first enzyme from an aerobic bacterium reducing succinic semialdehyde with high catalytic efficiency. As a novel succinic semialdehyde reductase, Gox1801 has the potential to be used in the biotechnological production of γ-hydroxybutyrate. PMID:25425279

  6. Elementary Mode Analysis for the Rational Design of Efficient Succinate Conversion from Glycerol by Escherichia coli

    PubMed Central

    Chen, Zhen; Liu, Hongjuan; Zhang, Jianan; Liu, Dehua

    2010-01-01

    By integrating the restriction of oxygen and redox sensing/regulatory system, elementary mode analysis was used to predict the metabolic potential of glycerol for succinate production by E. coli under either anaerobic or aerobic conditions. It was found that although the theoretical maximum succinate yields under both anaerobic and aerobic conditions are 1.0 mol/mol glycerol, the aerobic condition was considered to be more favorable for succinate production. Although increase of the oxygen concentration would reduce the succinate yield, the calculation suggests that controlling the molar fraction of oxygen to be under 0.65 mol/mol would be beneficial for increasing the succinate productivity. Based on the elementary mode analysis, the rational genetic modification strategies for efficient succinate production under aerobic and anaerobic conditions were obtained, respectively. Overexpressing the phosphoenolpyruvate carboxylase or heterogonous pyruvate carboxylase is considered to be the most efficient strategy to increase the succinate yield. PMID:20886007

  7. The development of carbamazepine-succinic acid cocrystal tablet formulations with improved in vitro and in vivo performance.

    PubMed

    Ullah, Majeed; Hussain, Izhar; Sun, Changquan Calvin

    2016-06-01

    The use of soluble cocrystal for delivering drugs with low solubility, although a potentially effective approach, often suffers the problem of rapid disproportionation during dissolution, which negates the solubility advantages offered by the cocrystal. This necessitates their robust stabilization in order for successful use in a tablet dosage form. The cocrystal between carbamezepine and succinic acid (CBZ-SUC) exhibits a higher aqueous solubility than its dihydrate, which is the stable form of CBZ in water. Using this model system, we demonstrate an efficient and material-sparing tablet formulation screening approach enabled by intrinsic dissolution rate measurements. Three tablet formulations capable of stabilizing the cocrystal both under accelerated condition of 40 °C and 75% RH and during dissolution were developed using three different polymers, Soluplus® (F1), Kollidon VA/64 (F2) and Hydroxypropyl methyl cellulose acetate succinate (F3). When compared to a marketed product, Epitol® 200 mg tablets (F0), drug release after 60 min from formulations F1 (∼82%), F2 (∼95%) and F3 (∼95%) was all higher than that from Epitol® (79%) in a modified simulated intestinal fluid. Studies in albino rabbits show correspondingly better bioavailability of F1-F3 than Epitol. PMID:26460090

  8. Acetate Dependence of Tumors

    PubMed Central

    Comerford, Sarah A.; Huang, Zhiguang; Du, Xinlin; Wang, Yun; Cai, Ling; Witkiewicz, Agnes; Walters, Holly; Tantawy, Mohammed N.; Fu, Allie; Manning, H. Charles; Horton, Jay D.; Hammer, Robert E.; McKnight, Steven L.; Tu, Benjamin P.

    2014-01-01

    SUMMARY Acetyl-CoA represents a central node of carbon metabolism that plays a key role in bioenergetics, cell proliferation and the regulation of gene expression. How highly glycolytic or hypoxic tumors are able to produce sufficient quantities of this metabolite to support cell growth and survival under nutrient-limiting conditions remains poorly understood. Here we show that the nucleocytosolic acetyl-CoA synthetase enzyme, ACSS2, supplies a key source of acetyl-CoA for tumors by capturing acetate as a carbon source. Despite exhibiting no gross deficits in growth or development, adult mice lacking ACSS2 exhibit a significant reduction in tumor burden in two different models of hepatocellular carcinoma. ACSS2 is expressed in a large proportion of human tumors and its activity is responsible for the majority of cellular acetate uptake into both lipids and histones. These observations may qualify ACSS2 as a targetable metabolic vulnerability of a wide spectrum of tumors. PMID:25525877

  9. Expression and specificity profile of the major acetate transporter AcpA in Aspergillus nidulans.

    PubMed

    Sá-Pessoa, Joana; Amillis, Sotiris; Casal, Margarida; Diallinas, George

    2015-03-01

    AcpA has been previously characterized as a high-affinity transporter essential for the uptake and use of acetate as sole carbon source in Aspergillus nidulans. Here, we follow the expression profile of AcpA and define its substrate specificity. AcpA-mediated acetate transport is detected from the onset of conidiospore germination, peaks at the time of germ tube emergence, and drops to low basal levels in germlings and young mycelia, where a second acetate transporter is also becoming apparent. AcpA activity also responds to acetate presence in the growth medium, but is not subject to either carbon or nitrogen catabolite repression. Short-chain monocarboxylates (benzoate, formate, butyrate and propionate) inhibit AcpA-mediated acetate transport with apparent inhibition constants (Ki) of 16.89±2.12, 9.25±1.01, 12.06±3.29 and 1.44±0.13mM, respectively. AcpA is also shown not to be directly involved in ammonia export, as proposed for its Saccharomyces cerevisiae homologue Ady2p. In the second part of this work, we search for the unknown acetate transporter expressed in mycelia, and for other transporters that might contribute to acetate uptake. In silico analysis, genetic construction of relevant null mutants, and uptake assays, reveal that the closest AcpA homologue (AN1839), named AcpB, is the 'missing' secondary acetate transporter in mycelia. We also identify two major short-chain carboxylate (lactate, succinate, pyruvate and malate) transporters, named JenA (AN6095) and JenB (AN6703), which however are not involved in acetate uptake. This work establishes a framework for further exploiting acetate and carboxylate transport in filamentous ascomycetes. PMID:25708319

  10. Development and validation of a stability indicating RP-HPLC method for simultaneous estimation of Olmesartan Medoxomil and Metoprolol Succinate in pharmaceutical dosage form

    PubMed Central

    Thakker, Nirmal M.; Panchal, Haresh B.; Rakholiya, Dinesh R.; Murugan, R.; Choudhari, Vishnu P.; Kuchekar, Bhanudas S.

    2012-01-01

    Aim and Backrgound: A simple, rapid, precise and isocratic RP-HPLC (Reverse Phase High Performance Liquid Chromatography) method is aimed to develop for the simultaneous estimation of Olmesartan Medoxomil and Metoprolol Succinate in bulk drug and pharmaceutical dosage form. Materials and Methods: The quantification is carried out using YMC-Pack CN (250 × 4.6 mm, 5.0 μm) column and the mobile phase comprises of 0.05% Trifluoro acetic acid (TFA) and Acetonitrile (ACN) (70:30 v/v). The flow rate is 1.0 ml/min. The eluent is monitored at 220 nm. The retention times of Olmesartan Medoxomil and Metoprolol Succinate are 7.9 min and 4.1 min respectively. The method is validated in terms of linearity, precision, accuracy, specificity, limit of detection and limit of quantitation. Results: Linearity and percentage recoveries of both Olmesartan Medoxomil and Metoprolol Succinate are in the range of 5-35 μg/ml and 100 ± 2%, respectively. The stress testing of both the drugs individually and their mixture is carried out under acidic, alkaline, oxidation, photo-stability and thermal degradation (dry heat and wet heat) conditions and its degradation products are well resolved from the analyte peaks. Conclusion: This method was successfully validated for accuracy, precision, and linearity. PMID:23781484

  11. Evaluation of an integrated biorefinery based on fractionation of spent sulphite liquor for the production of an antioxidant-rich extract, lignosulphonates and succinic acid.

    PubMed

    Alexandri, Maria; Papapostolou, Harris; Komaitis, Michael; Stragier, Lutgart; Verstraete, Willy; Danezis, Georgios P; Georgiou, Constantinos A; Papanikolaou, Seraphim; Koutinas, Apostolis A

    2016-08-01

    Spent sulphite liquor (SSL) has been used for the production of lignosulphonates (LS), antioxidants and bio-based succinic acid. Solvent extraction of SSL with isopropanol led to the separation of approximately 80% of the total LS content, whereas the fermentations carried out using the pretreated SSL with isopropanol led to the production of around 19g/L of succinic acid by both Actinobacillus succinogenes and Basfia succiniciproducens. Fractionation of SSL via nanofiltration to separate the LS and solvent extraction using ethyl acetate to separate the phenolic compounds produced a detoxified sugar-rich stream that led to the production of 39g/L of succinic acid by B. succiniciproducens. This fractionation scheme resulted also in the production of 32.4g LS and 1.15g phenolic-rich extract per 100g of SSL. Both pretreatment schemes removed significant quantities of metals and heavy metals. This novel biorefinery concept could be integrated in acidic sulphite pulping mills. PMID:27176670

  12. Global gene expression analysis of glucose overflow metabolism in Escherichia coli and reduction of aerobic acetate formation.

    PubMed

    Veit, Andrea; Polen, Tino; Wendisch, Volker F

    2007-02-01

    During aerobic growth on glucose, Escherichia coli produces acetate in the so-called overflow metabolism. DNA microarray analysis was used to determine the global gene expression patterns of chemostat cultivations of E. coli MG1655 that were characterized by different acetate formation rates during aerobic growth on glucose. A correlation analysis identified that expression of ten genes (sdhCDAB, sucB, sucC, acnB, lpdA, fumC and mdh) encoding the TCA cycle enzymes succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinyl-CoA synthetase, aconitase, fumarase and malate dehydrogenase, respectively, and of the acs-yjcH-actP operon for acetate utilization correlated negatively with acetate formation. Relieving transcriptional control of the sdhCDAB-b0725-sucABCD operon by chromosomal promoter exchange mutagenesis yielded a strain with increased specific activities of the TCA cycle enzymes succinate dehydrogenase, alpha-ketoglutarate dehydrogenase and succinyl-CoA synthetase, which are encoded by this operon. The resulting strain produced less acetate and directed more carbon towards carbon dioxide formation than the parent strain MG1655 while maintaining high growth and glucose consumption rates. PMID:17273855

  13. Succinate dehydrogenase subunit D and succinate dehydrogenase subunit B mutation analysis in canine phaeochromocytoma and paraganglioma.

    PubMed

    Holt, D E; Henthorn, P; Howell, V M; Robinson, B G; Benn, D E

    2014-07-01

    Phaeochromocytomas (PCs) are tumours of the adrenal medulla chromaffin cells. Paragangliomas (PGLs) arise in sympathetic ganglia (previously called extra-adrenal PCs) or in non-chromaffin parasympathetic ganglia cells that are usually non-secretory. Parenchymal cells from these tumours have a common embryological origin from neural crest ectoderm. Several case series of canine PCs and PGLs have been published and a link between the increased incidence of chemoreceptor neoplasia in brachycephalic dog breeds and chronic hypoxia has been postulated. A similar link to hypoxia in man led to the identification of germline heterozygous mutations in the gene encoding succinate dehydrogenase subunit D (SDHD) and subsequently SDHA, SDHB and SDHC in similar tumours. We investigated canine PCs (n = 6) and PGLs (n = 2) for SDHD and SDHB mutations and in one PGL found a somatic SDHD mutation c.365A>G (p.Lys122Arg) in exon 4, which was not present in normal tissue from this brachycephalic dog. Two PCs were heterozygous for both c.365A>G (p.Lys122Arg) mutation and an exon 3 silent variant c.291G>A. We also identified the heterozygous SDHB exon 2 mutation c.113G>A (p.Arg38Gln) in a PC. These results illustrate that genetic mutations may underlie tumourigenesis in canine PCs and PGLs. The spontaneous nature of these canine diseases and possible association of PGLs with hypoxia in brachycephalic breeds may make them an attractive model for studying the corresponding human tumours. PMID:24813157

  14. A novel organic nonlinear optical crystal: Creatininium succinate

    NASA Astrophysics Data System (ADS)

    Thirumurugan, R.; Anitha, K.

    2015-06-01

    A novel organic material complex of creatininium succinate (CS) has been synthesized and single crystals were grown by the reaction of creatinine and succinic acid from aqueous solution by employing the technique of slow evaporation at room temperature. The structure of the grown crystal has been elucidated using single crystal X-ray diffraction analysis and the structure was refined by least-squares method to R = 0.027 for 1840 reflections. FT-IR spectral investigation has been carried out to identify the various functional groups in the title compound. UV-Vis transmission was carried out which shows the crystal has a good optical transmittance in the visible region with lower cutoff wavelength around 220 nm. Nonlinear optical property of the crystal was confirmed by Kurtz-Perry powder technique.

  15. A novel organic nonlinear optical crystal: Creatininium succinate

    SciTech Connect

    Thirumurugan, R.; Anitha, K.

    2015-06-24

    A novel organic material complex of creatininium succinate (CS) has been synthesized and single crystals were grown by the reaction of creatinine and succinic acid from aqueous solution by employing the technique of slow evaporation at room temperature. The structure of the grown crystal has been elucidated using single crystal X-ray diffraction analysis and the structure was refined by least-squares method to R = 0.027 for 1840 reflections. FT-IR spectral investigation has been carried out to identify the various functional groups in the title compound. UV–Vis transmission was carried out which shows the crystal has a good optical transmittance in the visible region with lower cutoff wavelength around 220 nm. Nonlinear optical property of the crystal was confirmed by Kurtz-Perry powder technique.

  16. [The research progress of succinic acid fermentation strains].

    PubMed

    Wang, Qing-Zhao; Zhao, Xue-Ming

    2007-07-01

    The potential of succinic acid as an important chemical intermediates had been realized and fermentation is one of the best ways to make it possible in economical aspect. Fermentation organism is the key part of the fermentation method. The updated research developments of fermentation organisms and the fermentation characteristics and problems of them were reviewed and analyzed in this paper. Finally,the development future of fermenation organism was forecasted. PMID:17822024

  17. α-Tocopheryl Succinate as a Scaffold to Develop Potent Inhibitors of Breast Cancer Cell Adhesion

    PubMed Central

    Wang, Dasheng; Chuang, Hsiao-Ching; Weng, Shu-Chuan; Huang, Po-Hsien; Hsieh, Hao-Yu; Kulp, Samuel K.; Chen, Ching-Shih

    2009-01-01

    This study is aimed at the pharmacological exploitation of α-tocopheryl succinate (1) to develop potent anti-adhesion agents. Considering the structural cooperativity between the phytyl chain and the carboxylic terminus in determining the anti-adhesion activity, our structural optimization led to compound 5 ([2-(4,8-dimethyl-non-1-enyl)-2,5,7,8-tetramethyl-chroman-6-yloxy]-acetic acid), which exhibited an-order-of-magnitude higher potency than 1 in blocking the adhesion of 4T1 metastatic breast cancer cells to extracellular matrix proteins (IC50, 0.6 μM versus 10 μM). Evidence indicates that the ability of compound 5 to block cell adhesion and migration was attributable to its effect on disrupting focal adhesion and actin cytoskeletal integrity by facilitating the degradation of focal adhesion kinase. Interactions between tumor cells and the ECM in the tumor microenvironment have been increasingly recognized as critical modulators of the metastatic potential of tumor cells. Consequently, the ability of compound 5 to block such interactions provides a unique pharmacological tool to shed light onto mechanisms that govern cell adhesion and tumor metastasis. PMID:19708661

  18. The peculiarities of succinic acid production from rapeseed oil by Yarrowia lipolytica yeast.

    PubMed

    Kamzolova, Svetlana V; Vinokurova, Natalia G; Dedyukhina, Emiliya G; Samoilenko, Vladimir A; Lunina, Julia N; Mironov, Alexey A; Allayarov, Ramil K; Morgunov, Igor G

    2014-05-01

    The process of succinic acid (SA) production represents the combination of microbial synthesis of α-ketoglutaric acid from rapeseed oil by yeast Yarrowia lipolytica VKM Y-2412 and subsequent decarboxylation of α-ketoglutaric acid by hydrogen peroxide to SA that leads to the production of 69.0 g l(-1) of SA and 1.36 g l(-1) of acetic acid. SA was isolated from the culture broth filtrate in a crystalline form. The SA recovery from the culture filtrate has certain difficulties due to the presence of residual triglycerides of rapeseed oil. The effect of different methods of the culture filtrate treatment and various sorption materials on the coagulation of triglycerides was studied, and as a result, the precipitation of residual triglycerides by acetone was chosen. The subsequent isolation procedures involved the decomposition of H2O2 in the filtrate followed by filtrate bleaching and acidification with a mineral acid, evaporation of filtrate, and SA extraction with ethanol from the residue. The purity of crystalline SA isolated from the culture broth filtrate achieved 97.6-100 %. The product yield varied from 62.6 to 71.6 % depending on the acidity of the supernatant. PMID:24531240

  19. Characterization of the iron-sulfur centers in succinate dehydrogenase.

    PubMed Central

    Coles, C J; Holm, R H; Kurtz, D M; Orme-Johnson, W H; Rawlings, J; Singer, T P; Wong, G B

    1979-01-01

    Two techniques have been applied to the determination of the number and type (2-Fe, 4-Fe) of iron-sulfur centers in the iron-sulfur flavoprotein succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1]. One procedure uses p-CF3C6H4SH as an extrusion reagent and Fourier transform 19F nuclear magentic resonance as the method of detection and quantitation of extruded cores of these centers in the form of [Fe2S2(SRF)4]2- and [Fe4S4(SRF)4]2- (RF = p-C6H4CF3). The second procedure, interprotein core transfer, involves thiol displacement of iron-sulfur cores followed by specific core transfer to the apoproteins of Bacillus polymyxa ferredoxin and adrenodoxin. Detection and quantitation are accomplished by electron paramagnetic resonance of reduced proteins at low temperatures. Both procedures clearly show that succinate dehydrogenase contains two dimeric (Fe2S2) and one tetrameric (Fe4S4) centers per mole of histidyl flavin, accounting for all eight nonheme iron and eight labile sulfur atoms found by chemical analysis. These results remove uncertainties created by the less than stoichiometric amounts of binuclear centers detected by electron paramagnetic resonance after dithionite reduction and provide secure characterization of the iron-sulfur centers in this enzyme. PMID:226982

  20. Cell-permeable succinate prodrugs bypass mitochondrial complex I deficiency.

    PubMed

    Ehinger, Johannes K; Piel, Sarah; Ford, Rhonan; Karlsson, Michael; Sjövall, Fredrik; Frostner, Eleonor Åsander; Morota, Saori; Taylor, Robert W; Turnbull, Doug M; Cornell, Clive; Moss, Steven J; Metzsch, Carsten; Hansson, Magnus J; Fliri, Hans; Elmér, Eskil

    2016-01-01

    Mitochondrial complex I (CI) deficiency is the most prevalent defect in the respiratory chain in paediatric mitochondrial disease. This heterogeneous group of diseases includes serious or fatal neurological presentations such as Leigh syndrome and there are very limited evidence-based treatment options available. Here we describe that cell membrane-permeable prodrugs of the complex II substrate succinate increase ATP-linked mitochondrial respiration in CI-deficient human blood cells, fibroblasts and heart fibres. Lactate accumulation in platelets due to rotenone-induced CI inhibition is reversed and rotenone-induced increase in lactate:pyruvate ratio in white blood cells is alleviated. Metabolomic analyses demonstrate delivery and metabolism of [(13)C]succinate. In Leigh syndrome patient fibroblasts, with a recessive NDUFS2 mutation, respiration and spare respiratory capacity are increased by prodrug administration. We conclude that prodrug-delivered succinate bypasses CI and supports electron transport, membrane potential and ATP production. This strategy offers a potential future therapy for metabolic decompensation due to mitochondrial CI dysfunction. PMID:27502960

  1. Cell-permeable succinate prodrugs bypass mitochondrial complex I deficiency

    PubMed Central

    Ehinger, Johannes K.; Piel, Sarah; Ford, Rhonan; Karlsson, Michael; Sjövall, Fredrik; Frostner, Eleonor Åsander; Morota, Saori; Taylor, Robert W.; Turnbull, Doug M.; Cornell, Clive; Moss, Steven J.; Metzsch, Carsten; Hansson, Magnus J.; Fliri, Hans; Elmér, Eskil

    2016-01-01

    Mitochondrial complex I (CI) deficiency is the most prevalent defect in the respiratory chain in paediatric mitochondrial disease. This heterogeneous group of diseases includes serious or fatal neurological presentations such as Leigh syndrome and there are very limited evidence-based treatment options available. Here we describe that cell membrane-permeable prodrugs of the complex II substrate succinate increase ATP-linked mitochondrial respiration in CI-deficient human blood cells, fibroblasts and heart fibres. Lactate accumulation in platelets due to rotenone-induced CI inhibition is reversed and rotenone-induced increase in lactate:pyruvate ratio in white blood cells is alleviated. Metabolomic analyses demonstrate delivery and metabolism of [13C]succinate. In Leigh syndrome patient fibroblasts, with a recessive NDUFS2 mutation, respiration and spare respiratory capacity are increased by prodrug administration. We conclude that prodrug-delivered succinate bypasses CI and supports electron transport, membrane potential and ATP production. This strategy offers a potential future therapy for metabolic decompensation due to mitochondrial CI dysfunction. PMID:27502960

  2. Inhibitory effect of succinic acid on epithelial cell proliferation of colonic mucosa in rats.

    PubMed

    Inagaki, Akiko; Ichikawa, Hirofumi; Sakata, Takashi

    2007-08-01

    Microbial breakdown of carbohydrates in the large intestine mainly produces short-chain fatty acids (SCFA). SCFA stimulate epithelial cell proliferation of the digestive tract in vivo. Succinic acid sometimes accumulates in the colonic lumen. However, the effect of succinic acid on colonic epithelial cell proliferation is unknown. Thus, we planned to clarify the influence of succinic acid on colonic epithelial cell proliferation in vivo. We continuously administered infusate with or without succinic acid (100 mM) into the distal colon of rats for 6 d and measured accumulated mitosis per crypt of distal colon of these rats. Succinic acid infused into rat colons significantly inhibited colonic cell proliferation and reduced crypt size. These results clearly indicated the inhibitory effects of succinic acid on colonic epithelial cell proliferation in vivo. PMID:17934246

  3. Benzoate degradation via the ortho pathway in Alcaligenes eutrophus is perturbed by succinate.

    PubMed Central

    Ampe, F; Uribelarrea, J L; Aragao, G M; Lindley, N D

    1997-01-01

    During batch growth of Alcaligenes eutrophus on benzoate-plus-succinate mixtures, substrates were simultaneously metabolized, leading to a higher specific growth rate (mu = 0.56 h-1) than when a single substrate was used (mu = 0.51 h-1 for benzoate alone and 0.44 h-1 for succinate alone), without adversely affecting the growth yield (0.57 Cmol/Cmol). Flux distribution analysis revealed that succinate dehydrogenase most probably controls the rate of total succinate consumption (the maximum flux being 9.7 mmol.g-1.h-1). It is postulated that the relative consumption rate of each substrate is in part related to modified levels of gene expression but to a large extent is dependent upon the presence of succinate, end product of the beta-ketoadipate pathway. Indeed, the in vitro beta-ketoadipate-succinyl coenzyme A transferase activity was seen to be inhibited by succinate, a coproduct of the reaction. PMID:9212423

  4. Succinic acid production with metabolically engineered E. coli recovered from two-stage fermentation.

    PubMed

    Ma, Jiang-Feng; Jiang, Min; Chen, Ke-Quan; Xu, Bing; Liu, Shu-Wen; Wei, Ping; Ying, Han-Jie

    2010-10-01

    Escherichia coli AFP111 cells recovered from spent two-stage fermentation broth were investigated for additional production of succinic acid under anaerobic conditions. Recovered cells produced succinic acid in an aqueous environment with no nutrient supplementation except for glucose and MgCO(3). In addition, initial glucose concentration and cell density had a significant influence on succinic acid mass yield and productivity. Although the final concentration of succinic acid from recovered cells was lower than from two-stage fermentation, an average succinic acid mass yield of 0.85 g/g was achieved with an average productivity of 1.81 g/l h after three rounds of recycling, which was comparable to two-stage fermentation. These results suggested that recovered cells might be reused for the efficient production of succinic acid. PMID:20495946

  5. Acetic acid suppresses the increase in disaccharidase activity that occurs during culture of caco-2 cells.

    PubMed

    Ogawa, N; Satsu, H; Watanabe, H; Fukaya, M; Tsukamoto, Y; Miyamoto, Y; Shimizu, M

    2000-03-01

    To understand how blood glucose level is lowered by oral administration of vinegar, we examined effects of acetic acid on glucose transport and disaccharidase activity in Caco-2 cells. Cells were cultured for 15 d in a medium containing 5 mmol/L of acetic acid. This chronic treatment did not affect cell growth or viability, and furthermore, apoptotic cell death was not observed. Glucose transport, evaluated with a nonmetabolizable substrate, 3-O-methyl glucose, also was not affected. However, the increase of sucrase activity observed in control cells (no acetic acid) was significantly suppressed by acetic acid (P < 0.01). Acetic acid suppressed sucrase activity in concentration- and time-dependent manners. Similar treatments (5 mmol/L and 15 d) with other organic acids such as citric, succinic, L-maric, L-lactic, L-tartaric and itaconic acids, did not suppress the increase in sucrase activity. Acetic acid treatment (5 mmol/L and 15 d) significantly decreased the activities of disaccharidases (sucrase, maltase, trehalase and lactase) and angiotensin-I-converting enzyme, whereas the activities of other hydrolases (alkaline phosphatase, aminopeptidase-N, dipeptidylpeptidase-IV and gamma-glutamyltranspeptidase) were not affected. To understand mechanisms underlying the suppression of disaccharidase activity by acetic acid, Northern and Western analyses of the sucrase-isomaltase complex were performed. Acetic acid did not affect the de novo synthesis of this complex at either the transcriptional or translational levels. The antihyperglycemic effect of acetic acid may be partially due to the suppression of disaccharidase activity. This suppression seems to occur during the post-translational processing. PMID:10702577

  6. Collaborative regulation of CO2 transport and fixation during succinate production in Escherichia coli.

    PubMed

    Zhu, Li-Wen; Zhang, Lei; Wei, Li-Na; Li, Hong-Mei; Yuan, Zhan-Peng; Chen, Tao; Tang, Ya-Ling; Liang, Xin-Hua; Tang, Ya-Jie

    2015-01-01

    In Escherichia coli, succinic acid is synthesized by CO2 fixation-based carboxylation of C3 metabolites. A two-step process is involved in CO2 integration: CO2 uptake into the cell and CO2 fixation by carboxylation enzymes. The phosphoenolpyruvate (PEP) carboxylase (PPC) and carboxykinase (PCK) are two important carboxylation enzymes within the succinate synthetic pathway, while SbtA and BicA are two important bicarbonate transporters. In this study, we employed a dual expression system, in which genes regulating both CO2 uptake and fixation were co-overexpressed, or overexpressed individually to improve succinate biosynthesis. Active CO2 uptake was observed by the expression of SbtA or/and BicA, but the succinate biosynthesis was decreased. The succinate production was significantly increased only when a CO2 fixation gene (ppc or pck) and a CO2 transport gene (sbtA or bicA) were co-expressed. Co-expression of pck and sbtA provided the best succinate production among all the strains. The highest succinate production of 73.4 g L(-1) was 13.3%, 66.4% or 15.0% higher than that obtained with the expression of PCK, SbtA alone, or with empty plasmids, respectively. We believe that combined regulation of CO2 transport and fixation is critical for succinate production. Imbalanced gene expression may disturb the cellular metabolism and succinate production. PMID:26626308

  7. Collaborative regulation of CO2 transport and fixation during succinate production in Escherichia coli

    PubMed Central

    Zhu, Li-Wen; Zhang, Lei; Wei, Li-Na; Li, Hong-Mei; Yuan, Zhan-Peng; Chen, Tao; Tang, Ya-Ling; Liang, Xin-Hua; Tang, Ya-Jie

    2015-01-01

    In Escherichia coli, succinic acid is synthesized by CO2 fixation-based carboxylation of C3 metabolites. A two-step process is involved in CO2 integration: CO2 uptake into the cell and CO2 fixation by carboxylation enzymes. The phosphoenolpyruvate (PEP) carboxylase (PPC) and carboxykinase (PCK) are two important carboxylation enzymes within the succinate synthetic pathway, while SbtA and BicA are two important bicarbonate transporters. In this study, we employed a dual expression system, in which genes regulating both CO2 uptake and fixation were co-overexpressed, or overexpressed individually to improve succinate biosynthesis. Active CO2 uptake was observed by the expression of SbtA or/and BicA, but the succinate biosynthesis was decreased. The succinate production was significantly increased only when a CO2 fixation gene (ppc or pck) and a CO2 transport gene (sbtA or bicA) were co-expressed. Co-expression of pck and sbtA provided the best succinate production among all the strains. The highest succinate production of 73.4 g L−1 was 13.3%, 66.4% or 15.0% higher than that obtained with the expression of PCK, SbtA alone, or with empty plasmids, respectively. We believe that combined regulation of CO2 transport and fixation is critical for succinate production. Imbalanced gene expression may disturb the cellular metabolism and succinate production. PMID:26626308

  8. Fermentative Succinate Production: An Emerging Technology to Replace the Traditional Petrochemical Processes

    PubMed Central

    Cao, Yujin; Zhang, Rubing; Sun, Chao; Cheng, Tao; Liu, Yuhua; Xian, Mo

    2013-01-01

    Succinate is a valuable platform chemical for multiple applications. Confronted with the exhaustion of fossil energy resources, fermentative succinate production from renewable biomass to replace the traditional petrochemical process is receiving an increasing amount of attention. During the past few years, the succinate-producing process using microbial fermentation has been made commercially available by the joint efforts of researchers in different fields. In this review, recent attempts and experiences devoted to reduce the production cost of biobased succinate are summarized, including strain improvement, fermentation engineering, and downstream processing. The key limitations and challenges faced in current microbial production systems are also proposed. PMID:24396827

  9. [Nomegestrol acetate: clinical pharmacology].

    PubMed

    Lello, S

    2009-10-01

    Progestogens are used in clinical practice in some conditions. Their effects depend on their chemical structure, pharmacokinetics, pharmacodynamics, with important differences among various progestogens. Generally, progestins are classified according to their parent molecule, of which often they keep some features. Derivatives of 19-nor-progesterone are characterized by high selectivity of action on progestin receptor. In particular, nomegestrol acetate (NomAc) shows an important progestational potency, neutral gluco-lipid profile, and antigonadotropic activity. It is used for treating menstrual cycle disorders and for hormone replacement therapy in menopause in association with an estrogen. In future, thanks to its antigonadotropic activity, NomAc will be used in estroprogestin combinations in fertile women, thus taking advantage of its tolerability profile and obtaining numerous non-contraceptive benefits as well. PMID:19749678

  10. Isolation of acetic, propionic and butyric acid-forming bacteria from biogas plants.

    PubMed

    Cibis, Katharina Gabriela; Gneipel, Armin; König, Helmut

    2016-02-20

    In this study, acetic, propionic and butyric acid-forming bacteria were isolated from thermophilic and mesophilic biogas plants (BGP) located in Germany. The fermenters were fed with maize silage and cattle or swine manure. Furthermore, pressurized laboratory fermenters digesting maize silage were sampled. Enrichment cultures for the isolation of acid-forming bacteria were grown in minimal medium supplemented with one of the following carbon sources: Na(+)-dl-lactate, succinate, ethanol, glycerol, glucose or a mixture of amino acids. These substrates could be converted by the isolates to acetic, propionic or butyric acid. In total, 49 isolates were obtained, which belonged to the phyla Firmicutes, Tenericutes or Thermotogae. According to 16S rRNA gene sequences, most isolates were related to Clostridium sporosphaeroides, Defluviitoga tunisiensis and Dendrosporobacter quercicolus. Acetic, propionic or butyric acid were produced in cultures of isolates affiliated to Bacillus thermoamylovorans, Clostridium aminovalericum, Clostridium cochlearium/Clostridium tetani, C. sporosphaeroides, D. quercicolus, Proteiniborus ethanoligenes, Selenomonas bovis and Tepidanaerobacter sp. Isolates related to Thermoanaerobacterium thermosaccharolyticum produced acetic, butyric and lactic acid, and isolates related to D. tunisiensis formed acetic acid. Specific primer sets targeting 16S rRNA gene sequences were designed and used for real-time quantitative PCR (qPCR). The isolates were physiologically characterized and their role in BGP discussed. PMID:26779817

  11. Non-isothermal crystallization kinetics and characterization of biodegradable poly(butylene succinate-co-neopentyl glycol succinate) copolyesters.

    PubMed

    Xie, Wen-Jie; Zhou, Xiao-Ming

    2015-01-01

    Both biodegradable aliphatic neat poly(butylene succinate) (PBS) and poly(butylene succinate-co-neopentyl glycol succinate) (P(BS-co-NPGS)) copolyesters with different 1,4-butanediol/neopentyl glycol ratios were synthesized through a two-step process of transesterification and polycondensation using stannous chloride and 4-Methylbenzenesulfonic acid as the co-catalysts. The structure, non-isothermal crystallization behavior, crystalline morphology and crystal structure of neat PBS and P(BS-co-NPGS) copolyesters were characterized by (1)H NMR, differential scanning calorimetry (DSC), polarized optical microscope (POM) and wide angle X-ray diffraction (WAXD), respectively. The Avrami equation modified by Jeziorny and Mo's method was employed to describe the non-isothermal crystallization kinetics of the neat PBS and its copolyesters. The modified Avrami equation could adequately describe the primary stage of non-isothermal crystallization kinetics of the neat PBS and its copolyesters. Mo's method provided a fairly satisfactory description of the non-isothermal crystallization of neat PBS and its copolyesters. Interestingly, the values of 1/t1/2, Zc and F(T) obtained by the modified Avrami equation and Mo's method analysis indicated that the crystallization rate increased first and then decreased with an increase of NPGS content compared that of neat PBS, whereas the crystallization mechanism almost kept unchanged. The results of tensile testing showed that the ductility of PBS was largely improved by incorporating NPGS units. The elongation at break increased remarkably with increasing NPGS content. In particular, the sample with 20% NPGS content showed around 548% elongation at break. PMID:25491999

  12. Synthesis, characterization and nanocomposite formation of poly(glycerol succinate-co-maleate) with cellulose nanowhiskers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel biodegradable polymer based on glycerol, succinic anhydride and maleic anhydride, poly(glycerol succinate-co-maleate), poly(GlySAMA), was synthesized by melt polycondensation and tested as a matrix for composites with cellulose nanowhiskers. This glycerol-based polymer is thermally stable as...

  13. Study of the role of anaerobic metabolism in succinate production by Enterobacter aerogenes.

    PubMed

    Tajima, Yoshinori; Kaida, Kenichi; Hayakawa, Atsushi; Fukui, Keita; Nishio, Yousuke; Hashiguchi, Kenichi; Fudou, Ryosuke; Matsui, Kazuhiko; Usuda, Yoshihiro; Sode, Koji

    2014-09-01

    Succinate is a core biochemical building block; optimizing succinate production from biomass by microbial fermentation is a focus of basic and applied biotechnology research. Lowering pH in anaerobic succinate fermentation culture is a cost-effective and environmentally friendly approach to reducing the use of sub-raw materials such as alkali, which are needed for neutralization. To evaluate the potential of bacteria-based succinate fermentation under weak acidic (pH <6.2) and anaerobic conditions, we characterized the anaerobic metabolism of Enterobacter aerogenes AJ110637, which rapidly assimilates glucose at pH 5.0. Based on the profile of anaerobic products, we constructed single-gene knockout mutants to eliminate the main anaerobic metabolic pathways involved in NADH re-oxidation. These single-gene knockout studies showed that the ethanol synthesis pathway serves as the dominant NADH re-oxidation pathway in this organism. To generate a metabolically engineered strain for succinate production, we eliminated ethanol formation and introduced a heterogeneous carboxylation enzyme, yielding E. aerogenes strain ΔadhE/PCK. The strain produced succinate from glucose with a 60.5% yield (grams of succinate produced per gram of glucose consumed) at pH <6.2 and anaerobic conditions. Thus, we showed the potential of bacteria-based succinate fermentation under weak acidic conditions. PMID:24962116

  14. Integration of succinic acid and ethanol production within a corn or barley biorefinery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Production of succinic acid from glucose by Escherichia coli strain AFP184 was studied in a batch fermentor. The bases used for pH control included NaOH, KOH, NH4OH, and Na2CO3. The yield of succinic acid without and with carbon dioxide supplied by an adjacent ethanol fermentor using either corn or ...

  15. 40 CFR 721.10090 - Tertiary amine salt of glycol succinate (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Tertiary amine salt of glycol... Specific Chemical Substances § 721.10090 Tertiary amine salt of glycol succinate (generic). (a) Chemical... as tertiary amine salt of glycol succinate (PMN P-01-595) is subject to reporting under this...

  16. 40 CFR 721.10090 - Tertiary amine salt of glycol succinate (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Tertiary amine salt of glycol... Specific Chemical Substances § 721.10090 Tertiary amine salt of glycol succinate (generic). (a) Chemical... as tertiary amine salt of glycol succinate (PMN P-01-595) is subject to reporting under this...

  17. 40 CFR 721.10090 - Tertiary amine salt of glycol succinate (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Tertiary amine salt of glycol... Specific Chemical Substances § 721.10090 Tertiary amine salt of glycol succinate (generic). (a) Chemical... as tertiary amine salt of glycol succinate (PMN P-01-595) is subject to reporting under this...

  18. 40 CFR 721.10090 - Tertiary amine salt of glycol succinate (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Tertiary amine salt of glycol... Specific Chemical Substances § 721.10090 Tertiary amine salt of glycol succinate (generic). (a) Chemical... as tertiary amine salt of glycol succinate (PMN P-01-595) is subject to reporting under this...

  19. 40 CFR 721.10090 - Tertiary amine salt of glycol succinate (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Tertiary amine salt of glycol... Specific Chemical Substances § 721.10090 Tertiary amine salt of glycol succinate (generic). (a) Chemical... as tertiary amine salt of glycol succinate (PMN P-01-595) is subject to reporting under this...

  20. The effect of biotin on the production of succinic acid by Anaerobiospirillum succiniciproducens

    SciTech Connect

    Nghiem, N.P.; Davison, B.H.; Thompson, J.E.

    1995-07-01

    Succinic acid is an intermediate of the tricarboxylic acid (TCA) cycle, and therefore, is found in almost all plant and animal cells, albeit at very low concentrations. It has a very wide usage range, which includes applications in agriculture, food, medicine, plastics, cosmetics, textiles, plating and waste-gas scrubbing. Succinic acid currently is produced commercially by chemical processes. A fermentation process for its production is of great interest because in such process, renewable resources such as corn-derived glucose can be used as starting material. There is not a current biological process for the commercial production of succinic acid. Extensive efforts have been devoted to the isolation and screening of succinic acid-producing microorganisms. The anaerobic bacterium, Anaerobiospirillum succiniciproducens, is considered among the best direct succinic acid producers. A number of patents concerning the production of succinic acid by this organism have been issued. Our first attempt to develop a biological process for the production of succinic acid by A. succiniciproducens involved fermentation media improvement, in particular the use of supplemented nutrients. In this note, we show that higher yield of succinic acid could be achieved by supplementing the fermentation media with biotin, as a potential nutrient supplement representative.

  1. Structural basis for the binding of succinate to succinyl-CoA synthetase.

    PubMed

    Huang, Ji; Fraser, Marie E

    2016-08-01

    Succinyl-CoA synthetase catalyzes the only step in the citric acid cycle that provides substrate-level phosphorylation. Although the binding sites for the substrates CoA, phosphate, and the nucleotides ADP and ATP or GDP and GTP have been identified, the binding site for succinate has not. To determine this binding site, pig GTP-specific succinyl-CoA synthetase was crystallized in the presence of succinate, magnesium ions and CoA, and the structure of the complex was determined by X-ray crystallography to 2.2 Å resolution. Succinate binds in the carboxy-terminal domain of the β-subunit. The succinate-binding site is near both the active-site histidine residue that is phosphorylated in the reaction and the free thiol of CoA. The carboxy-terminal domain rearranges when succinate binds, burying this active site. However, succinate is not in position for transfer of the phosphoryl group from phosphohistidine. Here, it is proposed that when the active-site histidine residue has been phosphorylated by GTP, the phosphohistidine displaces phosphate and triggers the movement of the carboxylate of succinate into position to be phosphorylated. The structure shows why succinyl-CoA synthetase is specific for succinate and does not react appreciably with citrate nor with the other C4-dicarboxylic acids of the citric acid cycle, fumarate and oxaloacetate, but shows some activity with L-malate. PMID:27487822

  2. Succinate metabolism: a new therapeutic target for myocardial reperfusion injury.

    PubMed

    Pell, Victoria R; Chouchani, Edward T; Frezza, Christian; Murphy, Michael P; Krieg, Thomas

    2016-07-15

    Myocardial ischaemia/reperfusion (IR) injury is a major cause of death worldwide and remains a disease for which current clinical therapies are strikingly deficient. While the production of mitochondrial reactive oxygen species (ROS) is a critical driver of tissue damage upon reperfusion, the precise mechanisms underlying ROS production have remained elusive. More recently, it has been demonstrated that a specific metabolic mechanism occurs during ischaemia that underlies elevated ROS at reperfusion, suggesting a unifying model as to why so many different compounds have been found to be cardioprotective against IR injury. This review will discuss the role of the citric acid cycle intermediate succinate in IR pathology focusing on the mechanism by which this metabolite accumulates during ischaemia and how it can drive ROS production at Complex I via reverse electron transport. We will then examine the potential for manipulating succinate accumulation and metabolism during IR injury in order to protect the heart against IR damage and discuss targets for novel therapeutics designed to reduce reperfusion injury in patients. PMID:27194563

  3. Extraction chromatography of quadrivalent titanium and zirconium from succinate solution

    SciTech Connect

    Shete, S.D.; Shinde, V.M.

    1982-01-01

    Liquid ion exchangers such as tri-n-octyl amine (TOA), tri-iso-octylamine (TIOA) and Aliquat 336 have been used in this laboratory for analytical separation of vanadium(V) and niobium(V), indium(III), thalium(III), thorium(IV), cerium(IV) from succinate solutions. Extension of this study has revealed that benzene solutions of TOA, TIOA and Aliquat 336 could be used for anion exchange extraction of quadrivalent titanium and zirconium from succinate solution. The metal ions from the organic phase are stripped and determined spectrophotometrically. Solvent extraction methods for titanium(IV) and zirconium(IV) have been reviewed by De et al. and Korkisch in their monographs. Diethylamine, tri-ethylamine and tributylamine have been used for extraction of titanium from thiocyanate and citrate solution. Similarly high molecular weight amines such as TOA and TIOA have been used for the extraction of zirconium from mineral acids, but systematic solvent extraction separation of titanium(IV) and zirconium(IV) is lacking. In this communication we propose a new method for selective extraction and separation of titaium(IV) and zirconium(IV) from metal ions such as Mn, Cr, Mo, V, U, La, Ta, Th and Hf. The proposed method is comparatively free from drawbacks such as pre-equilibration of phases, multiple scrubbing, multiple extraction and coextraction of a large number of cations and anions.

  4. Stress induced reversible crystal transition in poly(butylene succinate)

    NASA Astrophysics Data System (ADS)

    Liu, Guoming; Zheng, Liuchun; Zhang, Xiuqin; Li, Chuncheng; Wang, Dujin

    2015-03-01

    The plastic deformation mechanism of semi-crystalline polymers is a long-studied topic, which is crucial for establishing structure/property relationships. For polymers with stress induced crystal transition, some open questions still need to be answered, such as on which stage of plastic deformation does the crystal transition take place, and more importantly, what happens on the lamellar structure during crystal transition. In this talk, stress-induced reversible crystal transition in poly(butylene succinate) was systematically investigated by in-situ WAXS and SAXS. A ``lamellar thickening'' phenomenon was observed during stretching, which was shown to mainly originated from the reversible crystal transition. This mechanism was shown to be valid in poly(ethylene succinate). The critical stress for the transition was measured in a series of PBS-based crystalline-amorphous multi-block copolymers. Interestingly, these PBS copolymers exhibited identical critical stress independent of amorphous blocks. The universal critical stress for crystal transition was interpreted through a single-microfibril-stretching mechanism. The work is financially supported by the National Natural Science Foundation of China (Grant No. 51203170).

  5. Emerging concepts in the flavinylation of succinate dehydrogenase.

    PubMed

    Kim, Hyung J; Winge, Dennis R

    2013-05-01

    The Succinate Dehydrogenase (SDH) heterotetrameric complex catalyzes the oxidation of succinate to fumarate in the tricarboxylic acid (TCA) cycle and in the aerobic respiratory chains of eukaryotes and bacteria. Essential in this catalysis is the covalently-linked cofactor flavin adenine dinucleotide (FAD) in subunit1 (Sdh1) of the SDH enzyme complex. The mechanism of FAD insertion and covalent attachment to Sdh1 is unknown. Our working concept of this flavinylation process has relied mostly on foundational works from the 1990s and by applying the principles learned from other enzymes containing a similarly linked FAD. The discovery of the flavinylation factor Sdh5, however, has provided new insight into the possible mechanism associated with Sdh1 flavinylation. This review focuses on encapsulating prior and recent advances towards understanding the mechanism associated with flavinylation of Sdh1 and how this flavinylation process affects the overall assembly of SDH. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease. PMID:23380393

  6. Simultaneous saccharification and fermentation of cassava to succinic acid by Escherichia coli NZN111.

    PubMed

    Chen, Cuixia; Ding, Shaopeng; Wang, Dezheng; Li, Zhimin; Ye, Qin

    2014-07-01

    In this study, the production of succinic acid from cassava starch and raw cassava instead of glucose by Escherichia coli NZN111 was investigated. During the two-stage fermentation, simultaneous saccharification and fermentation (SSF) was applied in the anaerobic stage. The results showed that both the productivity and specific productivity in the process conducted at 40°C were higher than those in the cultivation conducted at 37°C. The yield of succinic acid based on the amount of added starch reached the highest level 0.86 g/g and cassava starch was almost totally hydrolyzed in the SSF process. With the improved cell density, 127.13 g/L of succinic acid was obtained. When the liquefied crude cassava powder was used directly in SSF, 106.17 g/L of succinic acid was formed. The result showed that crude cassava powder could be another cheap raw material for succinic acid formation. PMID:24787322

  7. Thermochemical pretreatments for enhancing succinic acid production from industrial hemp (Cannabis sativa L.).

    PubMed

    Gunnarsson, Ingólfur B; Kuglarz, Mariusz; Karakashev, Dimitar; Angelidaki, Irini

    2015-04-01

    The aim of this study was to develop an efficient thermochemical method for treatment of industrial hemp biomass, in order to increase its bioconversion to succinic acid. Industrial hemp was subjected to various thermochemical pretreatments using 0-3% H2SO4, NaOH or H2O2 at 121-180°C prior to enzymatic hydrolysis. The influence of the different pretreatments on hydrolysis and succinic acid production by Actinobacillus succinogenes 130Z was investigated in batch mode, using anaerobic bottles and bioreactors. Enzymatic hydrolysis and fermentation of hemp material pretreated with 3% H2O2 resulted in the highest overall sugar yield (73.5%), maximum succinic acid titer (21.9 g L(-1)), as well as the highest succinic acid yield (83%). Results obtained clearly demonstrated the impact of different pretreatments on the bioconversion efficiency of industrial hemp into succinic acid. PMID:25682224

  8. Effect of Na sup + on intestinal succinate transport and metabolism in vitro

    SciTech Connect

    Moe, A.J.; Mallet, R.T.; Jackson, M.J.; Hollywood, J.A.; Kelleher, J.K. )

    1988-07-01

    The effect of Na{sup +} on {sup 14}CO{sub 2} production from ({sup 14}C)succinate was studied in isolated rat enterocytes, and Na{sup +}-dependent succinate transport was characterized in pig intestinal brush-border membrane vesicles. The production of {sup 14}CO{sub 2} from ({sup 14}C)succinate by enterocytes was decreased 12-fold when Na{sup +} was replaced by N-methyl-D-glucamine in the absence of glutamine and and 20-fold in the presence of 0.2 and 0.5 mM glutamine. The ratio of {sup 14}CO{sub 2} produced from (1,4-{sup 14}C)succinate to that produced by (2,3-{sup 14}C)succinate was not affected by Na{sup +} replacement, indicating that the pattern of tricarboxylic acid cycle metabolism was not altered. The uptake of ({sup 14}C)succinate by brush-border membrane vesicles was stimulated 10-fold in the presence of 100 mM NaCl compared with 100 mM KCl. When succinate uptake was corrected to transport into an osmotically sensitive space, the magnitude of the Na{sup +} stimulation was 20-fold. Succinate transport into brush-border membrane vesicles was Na{sup +} dependent, electroneutral, nonconcentrative, with an apparent Na{sup +}-succinate coupling ratio of 2:1. Results of this study indicate that Na{sup +}-stimulated CO{sub 2} production by enterocytes can be explained by the effect of Na{sup +} on succinate transport across the brush-border membrane.

  9. A note concerning acetate activation of peroxidative activity of catalases using 2,2'-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid as a substrate.

    PubMed

    Baker, Warren L; Key, Christopher; Lonergan, Greg T

    2005-01-01

    Beef liver catalases showed peroxidative activity using 2,2'-azino-bis-(3-ethylbenzthiazoline)-6-sulfonic acid as the electron donor and hydrogen peroxide as the acceptor at a pH of 5. This activity was not observed at pH 7. The reaction depended on acetate concentration, although succinate and propionate could partly replace the acetate as a catalyst. Other haem proteins also catalyzed a peroxidative effect. The reaction using syringaldazine or the coupling between dimethylaminobenzoic acid and 3-methyl-2-benzothiazolinone hydrazone was less effective and less sensitive. Evidence is presented that the reaction is associated with a conformational change of the catalase. PMID:15932252

  10. Nanoscale Concentration Quantification of Pharmaceutical Actives in Amorphous Polymer Matrices by Electron Energy-Loss Spectroscopy.

    PubMed

    Ricarte, Ralm G; Lodge, Timothy P; Hillmyer, Marc A

    2016-07-26

    We demonstrated the use of electron energy-loss spectroscopy (EELS) to evaluate the composition of phenytoin:hydroxypropyl methylcellulose acetate succinate (HPMCAS) spin-coated solid dispersions (SDs). To overcome the inability of bright-field and high-angle annular dark-field TEM imaging to distinguish between glassy drug and polymer, we used the π-π* transition peak in the EELS spectrum to detect phenytoin within the HPMCAS matrix of the SD. The concentration of phenytoin within SDs of 10, 25, and 50 wt % drug loading was quantified by a multiple least-squares analysis. Evaluating the concentration of 50 different regions in each SD, we determined that phenytoin and HPMCAS are intimately mixed at a length scale of 200 nm, even for drug loadings up to 50 wt %. At length scales below 100 nm, the variance of the measured phenytoin concentration increases; we speculate that this increase is due to statistical fluctuations in local concentration and chemical changes induced by electron irradiation. We also performed EELS analysis of an annealed 25 wt % phenytoin SD and showed that the technique can resolve concentration differences between regions that are less than 50 nm apart. Our findings indicate that EELS is a useful tool for quantifying, with high accuracy and sub-100 nm spatial resolution, the composition of many pharmaceutical and soft matter systems. PMID:27419264

  11. Biodegradation of poly(tetramethylene succinate-co-tetramethylene adipate) and poly(tetramethylene succinate) through water-soluble products.

    PubMed

    Kitakuni, E; Yoshikawa, K; Nakano, K; Sasuga, J; Nobiki, M; Naoi, H; Yokota, Y; Ishioka, R; Yakabe, Y

    2001-05-01

    Poly(tetramethylene succinate-co-tetramethylene adipate) (PBSA) and poly(tetramethylenesuccinate) (PBS) were hydrolyzed experimentally into water-soluble oligomers and monomers by Chromobacterium extracellular lipase. The oligomers were identified by high-performance liquid chromatography-mass spectrometry and 1H-nuclear magnetic resonance, which indicated that a total of 28 oligomer species were liberated from PBSA, and that 13 of them were identical to the hydrolysates from PBS. Moreover, 20 of the species were polyester-based compounds of monomer units, and the other 8 species were small amounts of diurethane compounds. Bis(hydroxybutyl) succinate (BSB) and bis(hydroxybutyl) hexamethylene dicarbamate (BHB) were the typical oligomers and were chemically synthesized. Biodegradability of BSB and BHB was examined for 28 d in the activated sludge, and analysis of the results of this study indicated that the final conversion rate of constituent carbon to carbon dioxide was estimated at 80 mol% for BSB and 10 mol% for BHB. The remaining amount of carbon in the undegraded BHB was 20 mol%. In the presence of BSB, the biodegradability of BHB was increased by about 1.5 times. The suggestion was made that BSB induced a growth of microorganisms and helped BHB degradation. This is consistent with the observation that the biodegradation of BHB in native soil for 60 d reached > 60%. PMID:11337881

  12. 21 CFR 184.1185 - Calcium acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... No. 62-54-4), also known as acetate of lime or vinegar salts, is the calcium salt of acetic acid. It may be produced by the calcium hydroxide neutralization of acetic acid. (b) The ingredient meets...

  13. Antibiofilm Properties of Acetic Acid

    PubMed Central

    Bjarnsholt, Thomas; Alhede, Morten; Jensen, Peter Østrup; Nielsen, Anne K.; Johansen, Helle Krogh; Homøe, Preben; Høiby, Niels; Givskov, Michael; Kirketerp-Møller, Klaus

    2015-01-01

    Bacterial biofilms are known to be extremely tolerant toward antibiotics and other antimicrobial agents. These biofilms cause the persistence of chronic infections. Since antibiotics rarely resolve these infections, the only effective treatment of chronic infections is surgical removal of the infected implant, tissue, or organ and thereby the biofilm. Acetic acid is known for its antimicrobial effect on bacteria in general, but has never been thoroughly tested for its efficacy against bacterial biofilms. In this article, we describe complete eradication of both Gram-positive and Gram-negative biofilms using acetic acid both as a liquid and as a dry salt. In addition, we present our clinical experience of acetic acid treatment of chronic wounds. In conclusion, we here present the first comprehensive in vitro and in vivo testing of acetic acid against bacterial biofilms. PMID:26155378

  14. Enhanced performance of alkylated graphene reinforced polybutylene succinate nanocomposite

    NASA Astrophysics Data System (ADS)

    Abidin, A. S. Zainal; Yusoh, K.; Jamari, S. S.; Abdullah, A. H.; Ismail, Z.

    2016-07-01

    Polybutylene succinate (PBS) was being grafted with octadecylamine-functionalized graphene oxide (GO-ODA) to produce novel PBS/GO-ODA nanocomposites by solution blending technique. Alkylated graphene oxide has superhydrophobic surface thus improved the affinity of the filler with low polar polymer such as PBS. The structure and compatibility of the filler and nanocomposites were being characterized using Fourier transform infrared spectroscopy (FTIR), Universal tensile machine (UTM) and thermogravimetric analysis (TGA). Enhancement of tensile strength and Young's modulus by 30% and 165% respectively was achieved with cooperation of 0.5% GO-ODA loading. The functionalization of GO-ODA in PBS matrix leads to the improvement in the nanocomposites properties.

  15. Succinic acid production from lignocellulosic hydrolysate by Basfia succiniciproducens.

    PubMed

    Salvachúa, Davinia; Smith, Holly; St John, Peter C; Mohagheghi, Ali; Peterson, Darren J; Black, Brenna A; Dowe, Nancy; Beckham, Gregg T

    2016-08-01

    The production of chemicals alongside fuels will be essential to enhance the feasibility of lignocellulosic biorefineries. Succinic acid (SA), a naturally occurring C4-diacid, is a primary intermediate of the tricarboxylic acid cycle and a promising building block chemical that has received significant industrial attention. Basfia succiniciproducens is a relatively unexplored SA-producing bacterium with advantageous features such as broad substrate utilization, genetic tractability, and facultative anaerobic metabolism. Here B. succiniciproducens is evaluated in high xylose-content hydrolysates from corn stover and different synthetic media in batch fermentation. SA titers in hydrolysate at an initial sugar concentration of 60g/L reached up to 30g/L, with metabolic yields of 0.69g/g, and an overall productivity of 0.43g/L/h. These results demonstrate that B. succiniciproducens may be an attractive platform organism for bio-SA production from biomass hydrolysates. PMID:27179951

  16. 2-Phenyl­biguanidinium hydrogen succinate methanol monosolvate

    PubMed Central

    Matulková, Irena; Císařová, Ivana; Němec, Ivan

    2010-01-01

    In the crystal of the title compound, C8H12N5 +·C4H5O4 −·CH3OH, the hydrogen succinate anions form infinite [010] chains via short, almost symmetrical, O⋯H⋯O hydrogen bonds. The 2-phenyl­biguanidium cations inter­connect these chains into layers lying parallel to the bc plane by way of N—H⋯O links. These planes only weakly inter­act in the direction of the a axis via C—H⋯π contacts between offset phenyl rings, leaving as much as 17% of the unit-cell volume accessible for the solvent. However, the methanol solvent mol­ecules could not be resolved due to extensive disorder and their assumed presence was removed from the overall scattering by the PLATON SQUEEZE procedure. PMID:21589482

  17. Protein-mediated assembly of succinate dehydrogenase and its cofactors.

    PubMed

    Van Vranken, Jonathan G; Na, Un; Winge, Dennis R; Rutter, Jared

    2015-01-01

    Succinate dehydrogenase (or complex II; SDH) is a heterotetrameric protein complex that links the tribarboxylic acid cycle with the electron transport chain. SDH is composed of four nuclear-encoded subunits that must translocate independently to the mitochondria and assemble into a mature protein complex embedded in the inner mitochondrial membrane. Recently, it has become clear that failure to assemble functional SDH complexes can result in cancer and neurodegenerative syndromes. The effort to thoroughly elucidate the SDH assembly pathway has resulted in the discovery of four subunit-specific assembly factors that aid in the maturation of individual subunits and support the assembly of the intact complex. This review will focus on these assembly factors and assess the contribution of each factor to the assembly of SDH. Finally, we propose a model of the SDH assembly pathway that incorporates all extant data. PMID:25488574

  18. SDHAF4 promotes mitochondrial succinate dehydrogenase activity and prevents neurodegeneration

    PubMed Central

    Van Vranken, Jonathan G.; Bricker, Daniel K.; Dephoure, Noah; Gygi, Steven P.; Cox, James E.; Thummel, Carl S.; Rutter, Jared

    2014-01-01

    SUMMARY Succinate dehydrogenase (SDH) occupies a central place in cellular energy production, linking the tricarboxylic cycle with the electron transport chain. As a result, a subset of cancers and neuromuscular disorders result from mutations affecting any of the four SDH structural subunits or either of two known SDH assembly factors. Herein we characterize a novel evolutionarily conserved SDH assembly factor designated Sdh8/SDHAF4, using yeast, Drosophila, and mammalian cells. Sdh8 interacts specifically with the catalytic Sdh1 subunit in the mitochondrial matrix, facilitating its association with Sdh2 and the subsequent assembly of the SDH holocomplex. These roles for Sdh8 are critical for preventing motility defects and neurodegeneration in Drosophila as well as the excess ROS generated by free Sdh1. These studies provide insights into the mechanisms by which SDH is assembled and raise the possibility that some forms of neuromuscular disease may be associated with mutations that affect this SDH assembly factor. PMID:24954416

  19. Protein-mediated assembly of succinate dehydrogenase and its cofactors

    PubMed Central

    Van Vranken, Jonathan G.; Na, Un; Winge, Dennis R.; Rutter, Jared

    2015-01-01

    Succinate dehydrogenase (or Complex II; SDH) is a heterotetrameric protein complex that links the tribarboxylic acid cycle with the electron transport chain. SDH is composed of four nuclear-encoded subunits that must translocate independently to the mitochondria and assemble into a mature protein complex embedded in the inner mitochondrial membrane. Recently, it has become clear that failure to assemble functional SDH complexes can result in cancer and neurodegenerative syndromes. The effort to thoroughly elucidate the SDH assembly pathway has resulted in the discovery of four subunit-specific assembly factors that aid in the maturation of individual subunits and support the assembly of the intact complex. This review will focus on these assembly factors and assess the contribution of each factor to the assembly of SDH. Finally, we propose a model of the SDH assembly pathway that incorporates all extant data. PMID:25488574

  20. Biologically produced succinic acid: A new route to chemical intermediates

    SciTech Connect

    Not Available

    1995-01-01

    The US Department of Energy (DOE) Alternative Feedstocks (AF) program is forging new links between the agricultural community and the chemicals industry through support of research and development (R & D) that uses `green` feedstocks to produce chemicals. The program promotes cost-effective industrial use of renewable biomass as feedstocks to manufacture high-volume chemical building blocks. Industrial commercialization of such processes would stimulate the agricultural sector by increasing the demand of agricultural and forestry commodities. New alternatives for American industry may lie in the nation`s forests and fields. The national laboratory consortium has undertaken a joint R&D project with the Michigan Biotechnology Institute to demonstrate the feasibility of producing a chemical intermediate, succinic acid, and various derivatives, from renewable agricultural resources.

  1. Cardiac-specific succinate dehydrogenase deficiency in Barth syndrome.

    PubMed

    Dudek, Jan; Cheng, I-Fen; Chowdhury, Arpita; Wozny, Katharina; Balleininger, Martina; Reinhold, Robert; Grunau, Silke; Callegari, Sylvie; Toischer, Karl; Wanders, Ronald Ja; Hasenfuß, Gerd; Brügger, Britta; Guan, Kaomei; Rehling, Peter

    2015-01-01

    Barth syndrome (BTHS) is a cardiomyopathy caused by the loss of tafazzin, a mitochondrial acyltransferase involved in the maturation of the glycerophospholipid cardiolipin. It has remained enigmatic as to why a systemic loss of cardiolipin leads to cardiomyopathy. Using a genetic ablation of tafazzin function in the BTHS mouse model, we identified severe structural changes in respiratory chain supercomplexes at a pre-onset stage of the disease. This reorganization of supercomplexes was specific to cardiac tissue and could be recapitulated in cardiomyocytes derived from BTHS patients. Moreover, our analyses demonstrate a cardiac-specific loss of succinate dehydrogenase (SDH), an enzyme linking the respiratory chain with the tricarboxylic acid cycle. As a similar defect of SDH is apparent in patient cell-derived cardiomyocytes, we conclude that these defects represent a molecular basis for the cardiac pathology in Barth syndrome. PMID:26697888

  2. Production of Succinic Acid from Citric Acid and Related Acids by Lactobacillus Strains

    PubMed Central

    Kaneuchi, Choji; Seki, Masako; Komagata, Kazuo

    1988-01-01

    A number of Lactobacillus strains produced succinic acid in de Man-Rogosa-Sharpe broth to various extents. Among 86 fresh isolates from fermented cane molasses in Thailand, 30 strains (35%) produced succinic acid; namely, 23 of 39 Lactobacillus reuteri strains, 6 of 18 L. cellobiosus strains, and 1 of 6 unidentified strains. All of 10 L. casei subsp. casei strains, 5 L. casei subsp. rhamnosus strains, 6 L. mali strains, and 2 L. buchneri strains did not produce succinic acid. Among 58 known strains including 48 type strains of different Lactobacillus species, the strains of L. acidophilus, L. crispatus, L. jensenii, and L. parvus produced succinic acid to the same extent as the most active fresh isolates, and those of L. alimentarius, L. collinoides, L. farciminis, L. fructivorans (1 of 2 strains tested), L. malefermentans, and L. reuteri were also positive, to lesser extents. Diammonium citrate in de Man-Rogosa-Sharpe broth was determined as a precursor of the succinic acid produced. Production rates were about 70% on a molar basis with two fresh strains tested. Succinic acid was also produced from fumaric and malic acids but not from dl-isocitric, α-ketoglutaric, and pyruvic acids. The present study is considered to provide the first evidence on the production of succinic acid, an important flavoring substance in dairy products and fermented beverages, from citrate by lactobacilli. PMID:16347795

  3. Activating phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase in combination for improvement of succinate production.

    PubMed

    Tan, Zaigao; Zhu, Xinna; Chen, Jing; Li, Qingyan; Zhang, Xueli

    2013-08-01

    Phosphoenolpyruvate (PEP) carboxylation is an important step in the production of succinate by Escherichia coli. Two enzymes, PEP carboxylase (PPC) and PEP carboxykinase (PCK), are responsible for PEP carboxylation. PPC has high substrate affinity and catalytic velocity but wastes the high energy of PEP. PCK has low substrate affinity and catalytic velocity but can conserve the high energy of PEP for ATP formation. In this work, the expression of both the ppc and pck genes was modulated, with multiple regulatory parts of different strengths, in order to investigate the relationship between PPC or PCK activity and succinate production. There was a positive correlation between PCK activity and succinate production. In contrast, there was a positive correlation between PPC activity and succinate production only when PPC activity was within a certain range; excessive PPC activity decreased the rates of both cell growth and succinate formation. These two enzymes were also activated in combination in order to recruit the advantages of each for the improvement of succinate production. It was demonstrated that PPC and PCK had a synergistic effect in improving succinate production. PMID:23747698

  4. ATP-Based Ratio Regulation of Glucose and Xylose Improved Succinate Production

    PubMed Central

    Zhang, Fengyu; Li, Jiaojiao; Liu, Huaiwei; Liang, Quanfeng; Qi, Qingsheng

    2016-01-01

    We previously engineered E. coli YL104H to efficiently produce succinate from glucose. Furthermore, the present study proved that YL104H could also co-utilize xylose and glucose for succinate production. However, anaerobic succinate accumulation using xylose as the sole carbon source failed, probably because of an insufficient supply of energy. By analyzing the ATP generation under anaerobic conditions in the presence of glucose or xylose, we indicated that succinate production was affected by the intracellular ATP level, which can be simply regulated by the substrate ratio of xylose to glucose. This finding was confirmed by succinate production using an artificial mixture containing different xylose to glucose ratios. Using xylose mother liquor, a waste containing both glucose and xylose derived from xylitol production, a final succinate titer of 61.66 g/L with an overall productivity of 0.95 g/L/h was achieved, indicating that the regulation of the intracellular ATP level may be a useful and efficient strategy for succinate production and can be extended to other anaerobic processes. PMID:27315279

  5. Effects of dissolved CO2 levels on the growth of Mannheimia succiniciproducens and succinic acid production.

    PubMed

    Song, Hyohak; Lee, Jeong Wook; Choi, Sol; You, Jong Kyun; Hong, Won Hi; Lee, Sang Yup

    2007-12-15

    A capnophilic rumen bacterium Mannheimia succiniciproducens produces succinic acid as a major fermentation end product under CO(2)-rich anaerobic condition. Since succinic acid is produced by carboxylation of C3 compounds during the fermentation, intracellular CO(2) availability is important for efficient succinic acid formation. Here, we investigated the metabolic responses of M. succiniciproducens to the different dissolved CO(2) concentrations (0-260 mM). Cell growth was severely suppressed when the dissolved CO(2) concentration was below 8.74 mM. On the other hand, cell growth and succinic acid production increased proportionally as the dissolved CO(2) concentration increased from 8.74 to 141 mM. The yields of biomass and succinic acid on glucose obtained at the dissolved CO(2) concentration of 141 mM were 1.49 and 1.52 times higher, respectively, than those obtained at the dissolved CO(2) concentration of 8.74 mM. It was also found that the additional CO(2) source provided in the form of NaHCO(3), MgCO(3), or CaCO(3) had positive effects on cell growth and succinic acid production. However, growth inhibition was observed when excessive bicarbonate salts were added. By the comparison of the activities of key enzymes, it was found that PEP carboxylation by PEP carboxykinase (PckA) is the most important for succinic acid production as well as the growth of M. succiniciproducens by providing additional ATP. PMID:17570706

  6. ATP-Based Ratio Regulation of Glucose and Xylose Improved Succinate Production.

    PubMed

    Zhang, Fengyu; Li, Jiaojiao; Liu, Huaiwei; Liang, Quanfeng; Qi, Qingsheng

    2016-01-01

    We previously engineered E. coli YL104H to efficiently produce succinate from glucose. Furthermore, the present study proved that YL104H could also co-utilize xylose and glucose for succinate production. However, anaerobic succinate accumulation using xylose as the sole carbon source failed, probably because of an insufficient supply of energy. By analyzing the ATP generation under anaerobic conditions in the presence of glucose or xylose, we indicated that succinate production was affected by the intracellular ATP level, which can be simply regulated by the substrate ratio of xylose to glucose. This finding was confirmed by succinate production using an artificial mixture containing different xylose to glucose ratios. Using xylose mother liquor, a waste containing both glucose and xylose derived from xylitol production, a final succinate titer of 61.66 g/L with an overall productivity of 0.95 g/L/h was achieved, indicating that the regulation of the intracellular ATP level may be a useful and efficient strategy for succinate production and can be extended to other anaerobic processes. PMID:27315279

  7. A method for determining thermophysical properties of organic material in aqueous solutions: Succinic acid

    NASA Astrophysics Data System (ADS)

    Riipinen, I.; Svenningsson, B.; Bilde, M.; Gaman, A.; Lehtinen, K. E. J.; Kulmala, M.

    2006-12-01

    A method for determining evaporation rates and thermodynamic properties of aqueous solution droplets is introduced. The method combines evaporation rate measurements using modified TDMA technique with data evaluation using an accurate evaporation model. The first set of data has been collected and evaluated for succinic acid aqueous solution droplets. Evaporation rates of succinic acid solution droplets have been measured using a TDMA system at controlled relative humidity (65%) and temperature (298 K). A temperature-dependent expression for the saturation vapour pressure of pure liquid phase succinic acid at atmospheric temperatures has been derived by analysing the evaporation rate data with a numerical model. The obtained saturation vapour pressure of liquid phase succinic acid is ln( p) = 118.41 - 16204.8/ T - 12.452ln( T). The vapour pressure is in unit of Pascal and the temperature in Kelvin. A linear expression for the enthalpy of vaporization for liquid state succinic acid is also presented. According to the results presented in the following, a literature expression for the vapour pressure of liquid phase succinic acid defined for temperatures higher than 461 K [Yaws, C.L., 2003. Yaws' Handbook of Thermodynamic and Physical Properties of Chemical Compounds, Knovel] can be extrapolated to atmospheric temperatures with very good accuracy. The results also suggest that at 298 K the mass accommodation coefficient of succinic acid is unity or very close to unity.

  8. Evaluation of Three Amorphous Drug Delivery Technologies to Improve the Oral Absorption of Flubendazole.

    PubMed

    Vialpando, Monica; Smulders, Stefanie; Bone, Scott; Jager, Casey; Vodak, David; Van Speybroeck, Michiel; Verheyen, Loes; Backx, Katrien; Boeykens, Peter; Brewster, Marcus E; Ceulemans, Jens; Novoa de Armas, Hector; Van Geel, Katrien; Kesselaers, Emma; Hillewaert, Vera; Lachau-Durand, Sophie; Meurs, Greet; Psathas, Petros; Van Hove, Ben; Verreck, Geert; Voets, Marieke; Weuts, Ilse; Mackie, Claire

    2016-09-01

    This study investigates 3 amorphous technologies to improve the dissolution rate and oral bioavailability of flubendazole (FLU). The selected approaches are (1) a standard spray-dried dispersion with hydroxypropylmethylcellulose (HPMC) E5 or polyvinylpyrrolidone-vinyl acetate 64, both with Vitamin E d-α-tocopheryl polyethylene glycol succinate; (2) a modified process spray-dried dispersion (MPSDD) with either HPMC E3 or hydroxypropylmethylcellulose acetate succinate (HPMCAS-M); and (3) confining FLU in ordered mesoporous silica (OMS). The physicochemical stability and in vitro release of optimized formulations were evaluated following 2 weeks of open conditions at 25°C/60% relative humidity (RH) and 40°C/75% RH. All formulations remained amorphous at 25°C/60% RH. Only the MPSDD formulation containing HPMCAS-M and 3/7 (wt./wt.) FLU/OMS did not crystallize following 40°C/75% RH exposure. The OMS and MPSDD formulations contained the lowest and highest amount of hydrolyzed degradant, respectively. All formulations were dosed to rats at 20 mg/kg in suspension. One FLU/OMS formulation was also dosed as a capsule blend. Plasma concentration profiles were determined following a single dose. In vivo findings show that the OMS capsule and suspension resulted in the overall highest area under the curve and Cmax values, respectively. These results cross-evaluate various amorphous formulations and provide a link to enhanced biopharmaceutical performance. PMID:27113473

  9. Succinate production from CO2-grown microalgal biomass as carbon source using engineered Corynebacterium glutamicum through consolidated bioprocessing

    PubMed Central

    Lee, Jungseok; Sim, Sang Jun; Bott, Michael; Um, Youngsoon; Oh, Min-Kyu; Woo, Han Min

    2014-01-01

    The potential for production of chemicals from microalgal biomass has been considered as an alternative route for CO2 mitigation and establishment of biorefineries. This study presents the development of consolidated bioprocessing for succinate production from microalgal biomass using engineered Corynebacterium glutamicum. Starch-degrading and succinate-producing C. glutamicum strains produced succinate (0.16 g succinate/g total carbon source) from a mixture of starch and glucose as a model microalgal biomass. Subsequently, the engineered C. glutamicum strains were able to produce succinate (0.28 g succinate/g of total sugars including starch) from pretreated microalgal biomass of CO2-grown Chlamydomonas reinhardtii. For the first time, this work shows succinate production from CO2 via sequential fermentations of CO2-grown microalgae and engineered C. glutamicum. Therefore, consolidated bioprocessing based on microalgal biomass could be useful to promote variety of biorefineries. PMID:25056811

  10. Rapid monomerization of poly(butylene succinate)-co-(butylene adipate) by Leptothrix sp.

    PubMed

    Nakajima-Kambe, Toshiaki; Toyoshima, Kieko; Saito, Chika; Takaguchi, Hitoshi; Akutsu-Shigeno, Yukie; Sato, Megumi; Miyama, Kazuyuki; Nomura, Nobuhiko; Uchiyama, Hiroo

    2009-12-01

    For rapid monomerization of biodegradable plastics, various microorganisms were screened and TB-71 was selected as the best strain. TB-71 degraded solid poly(butylene succinate)-co-(butylene adipate) (PBSA), poly(ethylene succinate), and poly(epsilon-caprolactone) but not poly(butylene succinate), poly(2-hydroxybutylate-co-valerate) or poly(lactic acid). Esterase activity was observed in the culture broth during PBSA degradation, which was specifically induced by PBSA. Analysis of the degradation products revealed that PBSA was degraded to monomers. PMID:19914585

  11. Comparative fluxome and metabolome analysis for overproduction of succinate in Escherichia coli.

    PubMed

    Taymaz-Nikerel, Hilal; De Mey, Marjan; Baart, Gino J E; Maertens, Jo; Foulquié-Moreno, Maria Remedios; Charlier, Daniel; Heijnen, Joseph J; van Gulik, Walter M

    2016-04-01

    An aerobic succinate-producing Escherichia coli mutant was compared to its wild-type by quantitatively analyzing both the metabolome and fluxome, during glucose-limited steady-state and succinate excess dynamic conditions, in order to identify targets for further strain engineering towards more efficient succinate production. The mutant had four functional mutations under the conditions investigated: increased expression of a succinate exporter (DcuC), deletion of a succinate importer (Dct), deletion of succinate dehydrogenase (SUCDH) and expression of a PEP carboxylase (PPC) with increased capacity due to a point mutation. The steady-state and dynamic patterns of the intracellular metabolite levels and fluxes in response to changes were used to locate the quantitative differences in the physiology/metabolism of the mutant strain. Unexpectedly the mutant had a higher energy efficiency, indicated by a much lower rate of oxygen consumption, under glucose-limited conditions, caused by the deletion of the transcription factors IclR and ArcA. Furthermore the mutant had a much lower uptake capacity for succinate (26-fold) and oxygen (17-fold under succinate excess) compared to the wild-type strain. The mutant strain produced 7.9 mmol.CmolX(-1) .h(-1) succinate during chemostat cultivation, showing that the choice of the applied genetic modifications was a successful strategy. Furthermore, the applied genetic modifications resulted in multiple large changes in metabolite levels (FBP, pyruvate, 6PG, NAD(+) /NADH ratio, α-ketogluarate) corresponding to large changes in fluxes. Compared to the wild-type a considerable flux shift occurred from the tricarboxylic acid (TCA) cycle to the oxidative part of the pentose phosphate pathway, including an inversion of the pyruvate kinase flux. The mutant responded very differently to excess of succinate, with a remarkable possible reversal of the TCA cycle. The mutant and the wild-type both showed homeostatic behaviour with respect

  12. Complete Oxidation of Propionate, Valerate, Succinate, and Other Organic Compounds by Newly Isolated Types of Marine, Anaerobic, Mesophilic, Gram-Negative, Sulfur-Reducing Eubacteria

    PubMed Central

    Finster, Kai; Bak, Friedhelm

    1993-01-01

    Anaerobic enrichment cultures with either propionate, succinate, lactate, or valerate and elemental sulfur and inocula from shallow marine or deep-sea sediments were dominated by rod-shaped motile bacteria after three transfers. By application of deep-agar dilutions, five eubacterial strains were obtained in pure culture and designated Kyprop, Gyprop, Kysw2, Gylac, and Kyval. All strains were gram negative and grew by complete oxidation of the electron donors and concomitant stoichiometric reduction of elemental sulfur to hydrogen sulfide. The isolates used acetate, propionate, succinate, lactate, pyruvate, oxaloacetate, maleate, glutamate, alanine, aspartate, and yeast extract. All isolates, except strain Gylac, used citrate as an electron donor but valerate was oxidized only by strain Kyval. Fumarate and malate were degraded by all strains without an additional electron donor or acceptor. Kyprop, Gyprop, and Gylac utilized elemental sulfur as the sole inorganic electron acceptor, while Kysw2 and Kyval also utilized nitrate, dimethyl sulfoxide, or Fe(III)-citrate as an electron acceptor. Images PMID:16348934

  13. Mechanistic differences in permeation behavior of supersaturated and solubilized solutions of carbamazepine revealed by nuclear magnetic resonance measurements.

    PubMed

    Ueda, Keisuke; Higashi, Kenjirou; Limwikrant, Waree; Sekine, Shuichi; Horie, Toshiharu; Yamamoto, Keiji; Moribe, Kunikazu

    2012-11-01

    A solid dispersion (SPD) of carbamazepine (CBZ) with hydroxypropyl methylcellulose acetate succinate (HPMC-AS) was prepared by the spray drying method. The apparent solubility (37 °C, pH 7.4) of CBZ observed with the SPD was over 3 times higher than the solubility of unprocessed CBZ. The supersaturated solution was stable for 7 days. A higher concentration of CBZ in aqueous medium was also achieved by mixing with Poloxamer 407 (P407), a solubilizing agent. From permeation studies of CBZ using Caco-2 monolayers and dialysis membranes, we observed improved CBZ permeation across the membrane in the supersaturated solution of CBZ/HPMC-AS SPD. On the contrary, the CBZ-solubilized P407 solution exhibited poor permeation by CBZ. The chemical shifts of CBZ on the (1)H NMR spectrum from CBZ/HPMC-AS SPD solution were not altered significantly by coexistence with HPMC-AS. In contrast, an upfield shift of CBZ was observed in the CBZ/P407 solution. The spin-lattice relaxation time (T(1)) over spin-spin relaxation time (T(2)) indicated that the mobility of CBZ in the HPMC-AS solution was much lower than that in water. Meanwhile, the mobility of CBZ in P407 solution was significantly higher than that in water. NMR data indicate that CBZ does not strongly interact with HPMC-AS. CBZ mobility was suppressed due to self-association and microviscosity around CBZ, which do not affect permeation behavior. Most of the CBZ molecules in the CBZ/P407 solution were solubilized in the hydrophobic core of P407, and a few were free to permeate the membrane. The molecular state of CBZ, as evaluated by NMR measurements, directly correlated with permeation behavior. PMID:22970935

  14. 21 CFR 172.765 - Succistearin (stearoyl propylene glycol hydrogen succinate).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... food in accordance with the following prescribed conditions: (a) The additive is the reaction product of succinic anhydride, fully hydrogenated vegetable oil (predominantly C16 or C18 fatty acid...

  15. Gut microbiota-produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance

    PubMed Central

    Ferreyra, Jessica A.; Wu, Katherine J.; Hryckowian, Andrew J.; Bouley, Donna M.; Weimer, Bart C.; Sonnenburg, Justin L.

    2016-01-01

    Summary Clostridium difficile is a leading cause of antibiotic-associated diarrhea. The mechanisms underlying C. difficile expansion after microbiota disturbance are just emerging. We assessed the gene expression profile of C. difficile within the intestine of gnotobiotic mice to identify genes regulated in response to either dietary or microbiota compositional changes. In the presence of the gut symbiont Bacteroides thetaiotaomicron, C. difficile induces a pathway that metabolizes the microbiota fermentation end-product succinate to butyrate. The low concentration of succinate in the microbiota of conventional mice is transiently elevated upon antibiotic treatment or chemically-induced intestinal motility disturbance, and C. difficile exploits this succinate spike to expand in the perturbed intestine. A C. difficile mutant compromised in succinate utilization is at a competitive disadvantage during these perturbations. Understanding the metabolic mechanisms involved in microbiota-C. difficile interactions may help to identify approaches for the treatment and prevention of C. difficile-associated diseases. PMID:25498344

  16. Quinone reduction by Rhodothermus marinus succinate:menaquinone oxidoreductase is not stimulated by the membrane potential

    SciTech Connect

    Fernandes, Andreia S.; Konstantinov, Alexander A.; Teixeira, Miguel; Pereira, Manuela M. . E-mail: mpereira@itqb.unl.pt

    2005-05-06

    Succinate:quinone oxidoreductase (SQR), a di-haem enzyme purified from Rhodothermus marinus, reveals an HQNO-sensitive succinate:quinone oxidoreductase activity with several menaquinone analogues as electron acceptors that decreases with lowering the redox midpoint potential of the quinones. A turnover with the low-potential 2,3-dimethyl-1,4-naphthoquinone that is the closest analogue of menaquinone, although low, can be detected in liposome-reconstituted SQR. Reduction of the quinone is not stimulated by an imposed K{sup +}-diffusion membrane potential of a physiological sign (positive inside the vesicles). Nor does the imposed membrane potential increase the reduction level of the haems in R. marinus SQR poised with the succinate/fumarate redox couple. The data do not support a widely discussed hypothesis on the electrogenic transmembrane electron transfer from succinate to menaquinone catalysed by di-haem SQRs. The role of the membrane potential in regulation of the SQR activity is discussed.

  17. Diesel lubricant composition containing 5-amino-triazole-succinic anhydride reaction product

    SciTech Connect

    Sung, R.L.; Zoleski, B.H.

    1981-03-17

    A diesel crankcase lubricant is described. It contains a lubricating oil base and the reaction product of a hydrocarbyl succinic anhydride. The hydrocarbyl radical has from 12 to 30 carbon atoms and 5-amino-triazole.

  18. Industrial Systems Biology of Saccharomyces cerevisiae Enables Novel Succinic Acid Cell Factory

    PubMed Central

    Otero, José Manuel; Cimini, Donatella; Patil, Kiran R.; Poulsen, Simon G.; Olsson, Lisbeth; Nielsen, Jens

    2013-01-01

    Saccharomyces cerevisiae is the most well characterized eukaryote, the preferred microbial cell factory for the largest industrial biotechnology product (bioethanol), and a robust commerically compatible scaffold to be exploitted for diverse chemical production. Succinic acid is a highly sought after added-value chemical for which there is no native pre-disposition for production and accmulation in S. cerevisiae. The genome-scale metabolic network reconstruction of S. cerevisiae enabled in silico gene deletion predictions using an evolutionary programming method to couple biomass and succinate production. Glycine and serine, both essential amino acids required for biomass formation, are formed from both glycolytic and TCA cycle intermediates. Succinate formation results from the isocitrate lyase catalyzed conversion of isocitrate, and from the α-keto-glutarate dehydrogenase catalyzed conversion of α-keto-glutarate. Succinate is subsequently depleted by the succinate dehydrogenase complex. The metabolic engineering strategy identified included deletion of the primary succinate consuming reaction, Sdh3p, and interruption of glycolysis derived serine by deletion of 3-phosphoglycerate dehydrogenase, Ser3p/Ser33p. Pursuing these targets, a multi-gene deletion strain was constructed, and directed evolution with selection used to identify a succinate producing mutant. Physiological characterization coupled with integrated data analysis of transcriptome data in the metabolically engineered strain were used to identify 2nd-round metabolic engineering targets. The resulting strain represents a 30-fold improvement in succinate titer, and a 43-fold improvement in succinate yield on biomass, with only a 2.8-fold decrease in the specific growth rate compared to the reference strain. Intuitive genetic targets for either over-expression or interruption of succinate producing or consuming pathways, respectively, do not lead to increased succinate. Rather, we demonstrate how

  19. 21 CFR 184.1185 - Calcium acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium acetate. 184.1185 Section 184.1185 Food and... Substances Affirmed as GRAS § 184.1185 Calcium acetate. (a) Calcium acetate (Ca (C2H3O2)2, CAS Reg. No. 62-54-4), also known as acetate of lime or vinegar salts, is the calcium salt of acetic acid. It may...

  20. Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis.

    PubMed

    Tretter, Laszlo; Patocs, Attila; Chinopoulos, Christos

    2016-08-01

    Succinate is an important metabolite at the cross-road of several metabolic pathways, also involved in the formation and elimination of reactive oxygen species. However, it is becoming increasingly apparent that its realm extends to epigenetics, tumorigenesis, signal transduction, endo- and paracrine modulation and inflammation. Here we review the pathways encompassing succinate as a metabolite or a signal and how these may interact in normal and pathological conditions.(1). PMID:26971832

  1. A complementary experimental and computational study of loxapine succinate and its monohydrate.

    PubMed

    Bhardwaj, Rajni M; Johnston, Blair F; Oswald, Iain D H; Florence, Alastair J

    2013-11-01

    The crystal structures of loxapine succinate [systematic name: 4-(2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-1-ium 3-carboxypropanoate], C18H19ClN3O(+)·C4H5O4(-), and loxapine succinate monohydrate {systematic name: bis[4-(2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-1-ium] succinate succinic acid dihydrate}, 2C18H19ClN3O(+)·C4H4O4(2-)·C4H6O4·2H2O, have been determined using X-ray powder diffraction and single-crystal X-ray diffraction, respectively. Fixed cell geometry optimization calculations using density functional theory confirmed that the global optimum powder diffraction derived structure also matches an energy minimum structure. The energy calculations proved to be an effective tool in locating the positions of the H atoms reliably and verifying the salt configuration of the structure determined from powder data. Crystal packing analysis of these structures revealed that the loxapine succinate structure is based on chains of protonated loxapine molecules while the monohydrate contains dispersion stabilized centrosymmetric dimers. Incorporation of water molecules within the crystal lattice significantly alters the molecular packing and protonation state of the succinic acid. PMID:24192171

  2. Immobilization of Actinobacillus succinogenes by adhesion or entrapment for the production of succinic acid.

    PubMed

    Corona-González, Rosa Isela; Miramontes-Murillo, Ricardo; Arriola-Guevara, Enrique; Guatemala-Morales, Guadalupe; Toriz, Guillermo; Pelayo-Ortiz, Carlos

    2014-07-01

    The production of succinic acid was studied with entrapped and adsorbed Actinobacillus succinogenes. The adsorption of fermentation products (organic acids in the concentration range of 1-20 g/L) on different supports was evaluated. It was found that succinic acid was adsorbed in small quantities on diatomite and zeolite (12.6 mg/g support). The highest production of succinic acid was achieved with A. succinogenes entrapped in agar beads. Batch fermentations with immobilized cells were carried out with glucose concentrations ranging from 20 to 80 g/L. Succinic acid (43.4 g/L) was obtained from 78.3g/L glucose, and a high productivity (2.83 g/Lh) was obtained with a glucose concentration of 37.6g/L. For repeated batch fermentations (5 cycles in 72 h) with immobilized cells in agar, the total glucose consumed was 147.55 g/L, while the production of succinic acid was 107 g/L. Immobilized cells reduced significantly the fermentation time, yield, productivity and final concentration of succinic acid. PMID:24844165

  3. Process development for the biological production of succinic acid and its derivatives from renewables

    SciTech Connect

    Davison, B.H.; Nghiem, N.P.

    1995-12-01

    The initial targets of the Alternative Feedstocks Program (AFP) are succinic acid and its derivatives. The first goal is to develop and demonstrate an integrated process for succinic acid production from renewable materials such as corn dextrose. A process has been identified to produce succinic acid by fermentation, purify it without precipitation, and convert it as an ester to butanediol. Four areas have been identified for improvement by focused research and development. These include (1) biocatalyst improvements through metabolic engineering, (2) bioreactor design, (3) separation/purification of succinic acid by membrane electrodialysis or adsorption, and (4) catalytic conversion of succinic acid to higher-valued chemicals such as butanediol. An essential element in this program is the on-going effort in process design, integration and economic assessment to evaluate the current process and the potential impacts of the proposed improvements. The AFP, which focuses on renewables-to-chemicals opportunities, is a joint effort between industry and a national laboratory team consisting of the National Renewable Energy Laboratory, Argonne National Laboratory, Idaho National Engineering Laboratory, Oak Ridge National Laboratory and Pacific Northwest Laboratory Michigan Biotechnology Institute is a collaborator on the succinic project.

  4. Succinic acid production from xylose mother liquor by recombinant Escherichia coli strain

    PubMed Central

    Wang, Honghui; Pan, Jiachuan; Wang, Jing; Wang, Nan; Zhang, Jie; Li, Qiang; Wang, Dan; Zhou, Xiaohua

    2014-01-01

    Succinic acid (1,4-butanedioic acid) is identified as one of important building-block chemicals. Xylose mother liquor is an abundant industrial residue in xylitol biorefining industry. In this study, xylose mother liquor was utilized to produce succinic acid by recombinant Escherichia coli strain SD121, and the response surface methodology was used to optimize the fermentation media. The optimal conditions of succinic acid fermentation were as follows: 82.62 g L−1 total initial sugars, 42.27 g L−1 MgCO3 and 17.84 g L−1 yeast extract. The maximum production of succinic acid was 52.09 ± 0.21 g L−1 after 84 h with a yield of 0.63 ± 0.03 g g−1 total sugar, approaching the predicted value (53.18 g L−1). It was 1.78-fold of the production of that obtained with the basic medium. This was the first report on succinic acid production from xylose mother liquor by recombinant E. coli strains with media optimization using response surface methodology. This work suggested that the xylose mother liquor could be an alternative substrate for the economical production of succinic acid by recombinant E. coli strains. PMID:26019590

  5. [Succinic acid production from sucrose and sugarcane molasses by metabolically engineered Escherichia coli].

    PubMed

    Li, Feng; Ma, Jiangfeng; Wu, Mingke; Ji, Yaliang; Chen, Wufang; Ren, Xinyi; Jiang, Min

    2015-04-01

    Sugarcane molasses containing large amounts of sucrose is an economical substrate for succinic acid production. However, Escherichia coli AFP111 cannot metabolize sucrose although it is a promising candidate for succinic acid production. To achieve sucrose utilizing ability, we cloned and expressed cscBKA genes encoding sucrose permease, fructokinase and invertase of non-PTS sucrose-utilization system from E. coli W in E. coli AFP111 to generate a recombinant strain AFP111/pMD19T-cscBKA. After 72 h of anaerobic fermentation of the recombinant in serum bottles, 20 g/L sucrose was consumed and 12 g/L succinic acid was produced. During dual-phase fermentation comprised of initial aerobic growth phase followed by anaerobic fermentation phase, the concentration of succinic acid from sucrose and sugarcane molasses was 34 g/L and 30 g/L, respectively, at 30 h of anaerobic phase in a 3 L fermentor. The results show that the introduction of non-PTS sucrose-utilization system has sucrose-metabolizing capability for cell growth and succinic acid production, and can use cheap sugarcane molasses to produce succinic acid. PMID:26380410

  6. Respiratory glycerol metabolism of Actinobacillus succinogenes 130Z for succinate production.

    PubMed

    Schindler, Bryan D; Joshi, Rajasi V; Vieille, Claire

    2014-09-01

    Actinobacillus succinogenes 130Z naturally produces among the highest levels of succinate from a variety of inexpensive carbon substrates. A few studies have demonstrated that A. succinogenes can anaerobically metabolize glycerol, a waste product of biodiesel manufacture and an inexpensive feedstock, to produce high yields of succinate. However, all these studies were performed in the presence of yeast extract, which largely removes the redox constraints associated with fermenting glycerol, a highly reduced molecule. We demonstrated that A. succinogenes cannot ferment glycerol in minimal medium, but that it can metabolize glycerol by aerobic or anaerobic respiration. These results were expected based on the A. succinogenes genome, which encodes respiratory enzymes, but no pathway for 1,3-propanediol production. We investigated A. succinogenes's glycerol metabolism in minimal medium in a variety of respiratory conditions by comparing growth, metabolite production, and in vitro activity of terminal oxidoreductases. Nitrate inhibited succinate production by inhibiting fumarate reductase expression. In contrast, growth in the presence of dimethylsulfoxide and in microaerobic conditions allowed high succinate yields. The highest succinate yield was 0.75 mol/mol glycerol (75 % of the maximum theoretical yield) in continuous microaerobic cultures. A. succinogenes could also grow and produce succinate on partially refined glycerols obtained directly from biodiesel manufacture. Finally, by expressing a heterologous 1,3-propanediol synthesis pathway in A. succinogenes, we provide the first proof of concept that A. succinogenes can be engineered to grow fermentatively on glycerol. PMID:25047181

  7. Production of succinic acid from oil palm empty fruit bunch cellulose using Actinobacillus succinogenes

    NASA Astrophysics Data System (ADS)

    Pasma, Satriani Aga; Daik, Rusli; Maskat, Mohamad Yusof

    2013-11-01

    Succinic acid is a common metabolite in plants, animals and microorganisms. It has been used widely in agricultural, food and pharmaceutical industries. Enzymatic hydrolysate glucose from oil palm empty fruit bunch (OPEFB) cellulose was used as a substrate for succinic acid production using Actinobacillus succinogenes. Using cellulose extraction from OPEFB can enhance the production of glucose as a main substrate for succinic acid production. The highest concentration of glucose produced from enzymatic hydrolysis is 167 mg/mL and the sugar recovery is 0.73 g/g of OPEFB. By optimizing the culture medium for succinic acid fermentation with enzymatic hydrolysate of OPEFB cellulose, the nitrogen sources could be reduced to just only 2.5 g yeast extract and 2.5 g corn step liquor. Batch fermentation was carried out using enzymatic hydrolysate of OPEFB cellulose with yeast extract, corn steep liquor and the salts mixture, 23.5 g/L succinic acid was obtained with consumption of 72 g/L glucose in enzymatic hydrolysate of OPEFB cellulose at 38 hours and 37°C. This study suggests that enzymatic hydrolysate of OPEFB cellulose maybe an alternative substrate for the efficient production of succinic acid by Actinobacillus succinogenes.

  8. Production of succinic acid from sucrose and sugarcane molasses by metabolically engineered Escherichia coli.

    PubMed

    Chan, Sitha; Kanchanatawee, Sunthorn; Jantama, Kaemwich

    2012-01-01

    Sucrose-utilizing genes (cscKB and cscA) from Escherichia coli KO11 were cloned and expressed in a metabolically engineered E. coli KJ122 to enhance succinate production from sucrose. KJ122 harboring a recombinant plasmid, pKJSUC, was screened for the efficient sucrose utilization by growth-based selection and adaptation. KJ122-pKJSUC-24T efficiently utilized sucrose in a low-cost medium to produce high succinate concentration with less accumulation of by-products. Succinate concentrations of 51 g/L (productivity equal to 1.05 g/L/h) were produced from sucrose in anaerobic bottles, and concentrations of 47 g/L were produced in 10L bioreactor within 48 h. Antibiotics had no effect on the succinate production by KJ122-pKJSUC-24T. In addition, succinate concentrations of 62 g/L were produced from sugarcane molasses in anaerobic bottles, and concentrations of 56 g/L in 10 L bioreactor within 72 h. These results demonstrated that KJ122-pKJSUC-24T would be a potential strain for bio-based succinate production from sucrose and sugarcane molasses. PMID:22023966

  9. Critical supersaturations for aerosol particles of succinic acid and its salts

    NASA Astrophysics Data System (ADS)

    Svenningsson, B.; Bilde, M.; Rosenørn, T.; Mønster, J.

    2003-04-01

    Dicarboxylic acids, like succinic acid, have been identified as important water soluble organic compounds in the atmosphere. Salts of carboxylic acids can be formed in the atmosphere in reactions between the acid and an inorganic salt. In this work we have studied the cloud droplet nucleating ability for succinic acid and some of its salts: disodium succinate, diammonium succinate and calcium succinate. A monodisperse aerosol was generated by atomizing a water solution of the compound of interest, drying the particles in diffusion driers and selecting a narrow size range using a differential mobility analyzer. The aerosol was then analyzed using a static thermal gradient cloud condensation nucleus spectrometer (CCNC-100B from the University of Wyoming). A CPC was used to count the number of particles as a reference. For a fixed particle diameter, the supersaturation was scanned to find a steep increase in the fraction of particles that were activated to cloud droplets. This critical supersaturation is compared with theoretical calculations using Köhler theory. Experimental critical supersaturations for succinic acid agree with Köhler theory with a van't Hoff factor of 1, i.e. it activates as if it does not dissociate. For the sodium salt, a van't Hoff factor of 2 fits laboratory data and theoretical calculations.

  10. Improving succinic acid production by Actinobacillus succinogenes from raw industrial carob pods.

    PubMed

    Carvalho, Margarida; Roca, Christophe; Reis, Maria A M

    2016-10-01

    Carob pods are an inexpensive by-product of locust bean gum industry that can be used as renewable feedstock for bio-based succinic acid. Here, for the first time, unprocessed raw carob pods were used to extract a highly enriched sugar solution, afterwards used as substrate to produce succinic acid using Actinobacillus succinogenes. Batch fermentations containing 30g/L sugars resulted in a production rate of 1.67gSA/L.h and a yield of 0.39gSA/g sugars. Taking advantage of A. succinogenes' metabolism, uncoupling cell growth from succinic acid production, a fed-batch mode was implemented to increase succinic acid yield and reduce by-products formation. This strategy resulted in a succinic acid yield of 0.94gSA/g sugars, the highest yield reported in the literature for fed-batch and continuous experiments, while maintaining by-products at residual values. Results demonstrate that raw carob pods are a highly efficient feedstock for bio-based succinic acid production. PMID:27394995

  11. Solid dispersion of quercetin in cellulose derivative matrices influences both solubility and stability.

    PubMed

    Li, Bin; Konecke, Stephanie; Harich, Kim; Wegiel, Lindsay; Taylor, Lynne S; Edgar, Kevin J

    2013-02-15

    Amorphous solid dispersions (ASD) of quercetin (Que) in cellulose derivative matrices, carboxymethylcellulose acetate butyrate (CMCAB), hydroxypropylmethylcellulose acetate succinate (HPMCAS), and cellulose acetate adipate propionate (CAAdP) were prepared with the goal of identifying an ASD that effectively increased Que aqueous solution concentration. Crystalline quercetin and Que/poly(vinylpyrrolidinone) (PVP) ASD were evaluated for comparison. Powder X-ray diffraction (XRPD) and differential scanning calorimetry (DSC) were used to examine the crystallinity of ASDs, physical mixtures (PM) and quercetin. ASDs were amorphous up to 50 wt% Que. Que stability against crystallization and solution concentrations from these ASDs were significantly higher than those observed for physical mixtures and crystalline Que. PVP stabilizes against both Que degradation and recrystallization; in contrast, these carboxylated cellulose derivatives inhibit recrystallization but release Que slowly. PVP ASDs afforded fast and complete drug release, while ASDs using these three cellulose derivatives provide slow, incomplete, pH-triggered drug release. PMID:23399255

  12. Influence of aqueous coatings on the stability of enteric coated pellets and tablets.

    PubMed

    Thoma, K; Bechtold, K

    1999-01-01

    Pancreatin pellets, placebo pellets and tablets containing vitamin B2 were coated with various aqueous and organic enteric polymers, HPMCAS, HP, Eudragit L 100-55, Eudragit L 30 D-55, CAP, CAT, CMEC and PVAP, comparatively investigated and tested for storage stability. With the exception of Eudragit L 100-55 and Eudragit L 30 D-55, higher amounts of coating material were needed to achieve gastro-resistance with aqueous coating than with organic coating. Film formation from aqueous dispersions of micronized HP 55 was affected by the degree of micronization and was improved by reducing the particle size of the polymer. Undercoating was another suitable measure to decrease the amount of coating material required. The choice of plasticizer was of special importance in the aqueous dispersions, and type and quantity must be appropriate for the polymer applied. Non-polymeric plasticizers such as triethyl citrate (TEC) evaporated along with water during the spraying or drying process and high temperatures promoted such losses. The moisture-sensitive pancreatic enzymes were damaged both by humidity and heat during aqueous coating. The extent of damage was dependent on the coating equipment used. Upon storage, coatings obtained from aqueous dispersions showed changes in enteric performance or release characteristics as a consequence of three chemical/physical mechanisms: hydrolysis of ester linkages in the polymer or plasticizer, evaporation of the plasticizer, delayed film formation. The active ingredient pancreatin induced hydrolysis of the ester based film-former hydroxypropyl methylcellulose acetate succinate (HPMCAS). However, even without the influence of enzymes, the phthalic ester groups of aqueous hydroxypropyl methylcellulose phthalate (HP) were partly cleaved after 11 months storage. In HPMCAS-coated pancreatin pellets, the plasticizer glyceryl triacetate was almost completely hydrolyzed by the enzymes, whilst triethyl citrate was lost by evaporation through

  13. [Succinate dehydrogenase (SDH)-deficient renal cell carcinoma].

    PubMed

    Agaimy, A

    2016-03-01

    Succinate dehydrogenase (SDH) represents a type II mitochondrial complex related to the respiratory chain and Krebs cycle. The complex is composed of four major subunits, SDHA, SDHB, SDHC and SDHD. The oncogenic role of this enzyme complex has only recently been recognized and the complex is currently considered an important oncogenic signaling pathway with tumor suppressor properties. In addition to the familial paraganglioma syndromes (types 1-5) as prototypical SDH-related diseases, many other tumors have been defined as SDH-deficient, in particular a subset of gastrointestinal stromal tumors (GIST), rare hypophyseal adenomas, a subset of pancreatic neuroendocrine neoplasms (recently added) and a variety of other tumor entities, the latter mainly described as rare case reports. As a central core subunit responsible for the integrity of the SDH complex, the expression of SDHB is lost in all SDH-deficient neoplasms irrespective of the specific SDH subunit affected by a genetic mutation in addition to concurrent loss of the subunit specifically affected by genetic alteration. Accordingly, all SDH-deficient neoplasms are by definition SDHB-deficient. The SDH-deficient renal cell carcinoma (RCC) has only recently been well-characterized and it is included as a specific subtype of RCC in the new World Health Organization (WHO) classification published in 2016. In this review, the major clinicopathological, immunohistochemical and genetic features of this rare disease entity are presented and discussed in the context of the broad differential diagnosis. PMID:26979428

  14. Mixed food waste as renewable feedstock in succinic acid fermentation.

    PubMed

    Sun, Zheng; Li, Mingji; Qi, Qingsheng; Gao, Cuijuan; Lin, Carol Sze Ki

    2014-11-01

    Mixed food waste, which was directly collected from restaurants without pretreatments, was used as a valuable feedstock in succinic acid (SA) fermentation in the present study. Commercial enzymes and crude enzymes produced from Aspergillus awamori and Aspergillus oryzae were separately used in hydrolysis of food waste, and their resultant hydrolysates were evaluated. For hydrolysis using the fungal mixture comprising A. awamori and A. oryzae, a nutrient-complete food waste hydrolysate was generated, which contained 31.9 g L(-1) glucose and 280 mg L(-1) free amino nitrogen. Approximately 80-90 % of the solid food waste was also diminished. In a 2.5 L fermentor, 29.9 g L(-1) SA was produced with an overall yield of 0.224 g g(-1) substrate using food waste hydrolysate and recombinant Escherichia coli. This is comparable to many similar studies using various wastes or by-products as substrates. Results of this study demonstrated the enormous potential of food waste as renewable resource in the production of bio-based chemicals and materials via microbial bioconversion. PMID:25149459

  15. Succinic semialdehyde dehydrogenase deficiency: Lessons from mice and men

    PubMed Central

    Pearl, P. L.; Gibson, K. M.; Cortez, M. A.; Wu, Y.; Snead, O. Carter; Knerr, I.; Forester, K.; Pettiford, J. M.; Jakobs, C.; Theodore, W. H.

    2009-01-01

    Summary Succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder of GABA degradation with subsequent elevations in brain GABA and GHB, is a neurometabolic disorder with intellectual disability, epilepsy, hypotonia, ataxia, sleep disorders, and psychiatric disturbances. Neuroimaging reveals increased T2-weighted MRI signal usually affecting the globus pallidus, cerebellar dentate nucleus, and subthalamic nucleus, and often cerebral and cerebellar atrophy. EEG abnormalities are usually generalized spike-wave, consistent with a predilection for generalized epilepsy. The murine phenotype is characterized by failure-to-thrive, progressive ataxia, and a transition from generalized absence to tonic-clonic to ultimately fatal convulsive status epilepticus. Binding and electrophysiological studies demonstrate use-dependent downregulation of GABA(A) and (B) receptors in the mutant mouse. Translational human studies similarly reveal downregulation of GABAergic activity in patients, utilizing flumazenil-PET and transcranial magnetic stimulation for GABA(A) and (B) activity, respectively. Sleep studies reveal decreased stage REM with prolonged REM latencies and diminished percentage of stage REM. An ad libitum ketogenic diet was reported as effective in the mouse model, with unclear applicability to the human condition. Acute application of SGS–742, a GABA(B) antagonist, leads to improvement in epileptiform activity on electrocorticography. Promising mouse data using compounds available for clinical use, including taurine and SGS–742, form the framework for human trials. PMID:19172412

  16. Biological denitrification using poly(butanediol succinate) as electron donor.

    PubMed

    Shen, Zhiqiang; Yin, Yanan; Wang, Jianlong

    2016-07-01

    Poly(butanediol succinate) (PBS), a biodegradable polymer, was used as both solid carbon source and biofilm carrier for biological nitrate removal process, in which PBS was filled in a packed-bed bioreactor. The denitrification performance and the microbial diversity of biofilm attached on the surface of PBS were investigated. The experimental results showed that the volumetric denitrification rate was 0.60 kg m(-3) day(-1) when NO3-N loading rate was 0.63 kg m(-3) day(-1), and the average NO2-N concentration was below 0.20 mg L(-1). The effluent pH value decreased slightly from a range of 6.98-7.87 to 6.46-7.18. The analysis of microbial community structure of biofilm by pyrosequencing method showed that Proteobacteria was the most abundant phylum (89.87 %), and β-Proteobacteria represented the most abundant class. Among the 76 identified genera, Dechloromonas (10.26 %), Alicycliphilus (9.15 %), Azospira (8.92 %), and Sinobacteraceae-uncultured (8.75 %) were the abundant genera. PBS, as a promising alternative carbon source, is a suitable solid carbon source and biofilm carrier for nitrate removal. PMID:26960320

  17. Radioprotective properties of tocopherol succinate against ionizing radiation in mice

    PubMed Central

    Singh, Vijay K.; Singh, Pankaj K.; Wise, Stephen Y.; Posarac, Ana; Fatanmi, Oluseyi O.

    2013-01-01

    Threats of nuclear and other radiologic exposures have been increasing but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. In prior publications we have demonstrated the efficacy of tocopherol succinate (TS) as a promising radiation countermeasure with the potential to protect against lethal doses of ionizing radiation exposure. The aim of this study was to gain further insight regarding how TS protects mice against a lethal dose of radiation. CD2F1 mice were injected subcutaneously with 400 mg/kg of TS, and 24 h later exposed to 60Co γ–radiation. Intestinal tissues or spleen/thymus were harvested after irradiation and analyzed for CD68-positive inflammatory cells and apoptotic cells by immunostaining of jejunal cross-sections. Comet assay was used to analyze DNA damage in various tissues. Phospho-histone H3(pH3) and the proliferating cell nuclear antigen (PCNA) were used as mitotic markers for immunostaining jejunal cross-sections. We observed that injecting TS significantly decreased the number of CD68-positive cells, DNA damage and apoptotic cells (BAX, caspase 3 and cleaved poly(ADP-ribose) polymerase-positive cells) as judged by various apoptotic pathway markers. TS treatment also increased proliferating cells in irradiated mice. Results of this study further support our contention that TS protects mice against lethal doses of ionizing radiation by inhibiting radiation-induced apoptosis and DNA damage while enhancing cell proliferation. PMID:23038797

  18. Succinate Dehydrogenase Deficiency in Pediatric and Adult Gastrointestinal Stromal Tumors

    PubMed Central

    Belinsky, Martin G.; Rink, Lori; von Mehren, Margaret

    2013-01-01

    Gastrointestinal stromal tumors (GISTs) in adults are generally driven by somatic gain-of-function mutations in KIT or PDGFRA, and biological therapies targeted to these receptor tyrosine kinases comprise part of the treatment regimen for metastatic and inoperable GISTs. A minority (10–15%) of GISTs in adults, along with ∼85% of pediatric GISTs, lacks oncogenic mutations in KIT and PDGFRA. Not surprisingly these wild type (WT) GISTs respond poorly to kinase inhibitor therapy. A subset of WT GISTs shares a set of distinguishing clinical and pathological features, and a flurry of recent reports has convincingly demonstrated shared molecular characteristics. These GISTs have a distinct transcriptional profile including over-expression of the insulin-like growth factor-1 receptor, and exhibit deficiency in the succinate dehydrogenase (SDH) enzyme complex. The latter is often but not always linked to bi-allelic inactivation of SDH subunit genes, particularly SDHA. This review will summarize the molecular, pathological, and clinical connections that link this group of SDH-deficient neoplasms, and offer a view toward understanding the underlying biology of the disease and the therapeutic challenges implicit to this biology. PMID:23730622

  19. Desmopressin Acetate in Intracranial Haemorrhage

    PubMed Central

    Kapapa, Thomas; Röhrer, Stefan; Struve, Sabine; Petscher, Matthias; König, Ralph; Wirtz, Christian Rainer; Woischneck, Dieter

    2014-01-01

    Introduction. The secondary increase in the size of intracranial haematomas as a result of spontaneous haemorrhage or trauma is of particular relevance in the event of prior intake of platelet aggregation inhibitors. We describe the effect of desmopressin acetate as a means of temporarily stabilising the platelet function. Patients and Methods. The platelet function was analysed in 10 patients who had received single (N = 4) or multiple (N = 6) doses of acetylsalicylic acid and 3 patients (control group) who had not taken acetylsalicylic acid. All subjects had suffered intracranial haemorrhage. Analysis was performed before, half an hour and three hours after administration of desmopressin acetate. Statistical analysis was performed by applying a level of significance of P ≤ 0.05. Results. (1) Platelet function returned to normal 30 minutes after administration of desmopressin acetate. (2) The platelet function worsened again after three hours. (3) There were no complications related to electrolytes or fluid balance. Conclusion. Desmopressin acetate can stabilise the platelet function in neurosurgical patients who have received acetylsalicylic acid prior to surgery without causing transfusion-related side effects or a loss of time. The effect is, however, limited and influenced by the frequency of drug intake. Further controls are needed in neurosurgical patients. PMID:25610644

  20. Desvenlafaxine succinate ameliorates visceral hypersensitivity but delays solid gastric emptying in rats.

    PubMed

    Dai, Fei; Lei, Yong; Li, Shiying; Song, Gengqing; Chen, Jiande D Z

    2013-08-15

    Desvenlafaxine succinate (DVS) is a novel serotonin and norepinephrine reuptake inhibitor. The aim of this study was to investigate the effects of DVS on visceral hypersensitivity and solid gastric emptying in a rodent model of gastric hyperalgesia. Twenty-eight gastric hyperalgesia rats and 20 control rats were used. Visceral sensitivity during gastric distention (GD) was assessed by recording of electromyogram (EMG) at pressures of 20, 40, 60, and 80 mmHg. DVS with doses of 1, 10, and 30 mg/kg were administrated by gavage, 5-HT1A antagonist (WAY-100635, 0.3 mg/kg) was given subcutaneously, and 5-HT2A antagonist (ketanserin, 1 mg/kg) was given intraperitoneally. The level of norepinephrine in plasma was measured by enzyme-linked immunosorbent assay. We found that 1) visceral hypersensitivity induced by acetic acid was validated. 2) DVS dose-dependently reduced visceral hypersensitivity in the gastric hypersensitivity rats. The EMG (% of baseline value without GD) during GD at 60 and 80 mmHg with DVS at a dose of 30 mg/kg were 119.4 ± 2.3% (vs. saline 150.9 ± 2.7%, P < 0.001) and 128.2 ± 3.2% (vs. saline 171.1 ± 2.4%, P < 0.001). Similar findings were observed at a dose of 10 mg/kg. DVS at a dose of 1 mg/kg reduced visceral hypersensitivity only during GD at 60 mmHg. 3) Neither WAY-100635 nor ketanserin blocked the effect of DVS on visceral sensitivity. 4) DVS at 30 mg/kg significantly increased plasma NE level (P = 0.012 vs. saline). 5) DVS at 30 mg/kg significantly delayed solid gastric emptying (P < 0.05 vs. saline). We conclude that DVS reduces visceral sensitivity in a rodent model of visceral hypersensitivity and delays solid gastric emptying. Caution should be made when DVS is used for treating patients. PMID:23764892

  1. Reductive opening of carbohydrate phenylsulfonylethylidene (PSE) acetals.

    PubMed

    Chéry, Florence; Cabianca, Elena; Tatibouët, Arnaud; De Lucchi, Ottorino; Lindhorst, Thisbe K; Rollin, Patrick

    2015-11-19

    The phenylsulfonylethylidene (PSE) acetal is a relatively new protecting group in carbohydrate chemistry. However, carbohydrate-derived phenylsulfonylethylidene (PSE) acetals show a different behavior in reductive desulfonylation than simple symmetrical acetals. Here we have investigated various SET-type reaction conditions in order to open PSE acetals regioselectively and to produce chiral ω-hydroxyethenyl ethers. Whereas sodium amalgam leads to a mixture of regioisomeric vinyl ethers besides the ethylidene acetal, samarium iodide is suited for regioselective ring opening. This is shown with seven different carbohydrate PSE acetals, both of the 1,3-dioxane and the 1,3-dioxolane type. PMID:26469209

  2. Conversion of succinic acid to 1,4-butanediol via dimethyl succinate over rhenium nano-catalyst supported on copper-containing mesoporous carbon.

    PubMed

    Hong, Ung Gi; Kim, Jeong Kwon; Lee, Joongwon; Lee, Jong Kwon; Yi, Jongheop; Song, In Kyu

    2014-11-01

    Copper-containing mesoporous carbons (XCu-MC) with different copper content (X = 8.0, 12.7, 15.9, 23.3, and 26.8 wt%) were prepared by a single-step surfactant-templating method. Rhenium nano-catalysts supported on copper-containing mesoporous carbons (Re/XCu-MC) were then prepared by an incipient wetness method. Re/XCu-MC (X = 8.0, 12.7, 15.9, 23.3, and 26.8 wt%) catalysts were characterized by nitrogen adsorption-desorption isotherm, HR-TEM, FT-IR, and H2- TPR analyses. Liquid-phase hydrogenation of succinic acid to 1,4-butanediol (BDO) via dimethyl succinate (DMS) was carried out over Re/XCu-MC catalysts in a batch reactor. The effect of copper content on the physicochemical properties and catalytic activities of Re/XCu-MC catalysts in the hydrogenation of succinic acid to BDO was investigated. Re/XCu-MC catalysts retained different physicochemical properties depending on copper content. In the hydrogenation of succinic acid to BDO, yield for BDO showed a volcano-shaped trend with respect to copper content. Thus, an optimal copper content was required to achieve maximum catalytic performance of Re/XCu-MC. It was also observed that yield for BDO increased with increasing the amount of hydrogen consumption by copper in the Re/XCu-MC catalysts. PMID:25958619

  3. Bio-oil based biorefinery strategy for the production of succinic acid

    PubMed Central

    2013-01-01

    Background Succinic acid is one of the key platform chemicals which can be produced via biotechnology process instead of petrochemical process. Biomass derived bio-oil have been investigated intensively as an alternative of diesel and gasoline fuels. Bio-oil could be fractionized into organic phase and aqueous phase parts. The organic phase bio-oil can be easily upgraded to transport fuel. The aqueous phase bio-oil (AP-bio-oil) is of low value. There is no report for its usage or upgrading via biological methods. In this paper, the use of AP-bio-oil for the production of succinic acid was investigated. Results The transgenic E. coli strain could grow in modified M9 medium containing 20 v/v% AP-bio-oil with an increase in OD from 0.25 to 1.09. And 0.38 g/L succinic acid was produced. With the presence of 4 g/L glucose in the medium, succinic acid concentration increased from 1.4 to 2.4 g/L by addition of 20 v/v% AP-bio-oil. When enzymatic hydrolysate of corn stover was used as carbon source, 10.3 g/L succinic acid was produced. The obtained succinic acid concentration increased to 11.5 g/L when 12.5 v/v% AP-bio-oil was added. However, it decreased to 8 g/L when 50 v/v% AP-bio-oil was added. GC-MS analysis revealed that some low molecular carbon compounds in the AP-bio-oil were utilized by E. coli. Conclusions The results indicate that AP-bio-oil can be used by E. coli for cell growth and succinic acid production. PMID:23657107

  4. Geobacter sulfurreducens sp. nov., a hydrogen- and acetate-oxidizing dissimilatory metal-reducing microorganism.

    PubMed Central

    Caccavo, F; Lonergan, D J; Lovley, D R; Davis, M; Stolz, J F; McInerney, M J

    1994-01-01

    A dissimilatory metal- and sulfur-reducing microorganism was isolated from surface sediments of a hydrocarbon-contaminated ditch in Norman, Okla. The isolate, which was designated strain PCA, was an obligately anaerobic, nonfermentative nonmotile, gram-negative rod. PCA grew in a defined medium with acetate as an electron donor and ferric PPi, ferric oxyhydroxide, ferric citrate, elemental sulfur, Co(III)-EDTA, fumarate, or malate as the sole electron acceptor. PCA also coupled the oxidation of hydrogen to the reduction of Fe(III) but did not reduce Fe(III) with sulfur, glucose, lactate, fumarate, propionate, butyrate, isobutyrate, isovalerate, succinate, yeast extract, phenol, benzoate, ethanol, propanol, or butanol as an electron donor. PCA did not reduce oxygen, Mn(IV), U(VI), nitrate, sulfate, sulfite, or thiosulfate with acetate as the electron donor. Cell suspensions of PCA exhibited dithionite-reduced minus air-oxidized difference spectra which were characteristic of c-type cytochromes. Phylogenetic analysis of the 16S rRNA sequence placed PCA in the delta subgroup of the proteobacteria. Its closest known relative is Geobacter metallireducens. The ability to utilize either hydrogen or acetate as the sole electron donor for Fe(III) reduction makes strain PCA a unique addition to the relatively small group of respiratory metal-reducing microorganisms available in pure culture. A new species name, Geobacter sulfurreducens, is proposed. Images PMID:7527204

  5. Structural and functional consequences of succinate dehydrogenase subunit B mutations.

    PubMed

    Kim, E; Rath, E M; Tsang, V H M; Duff, A P; Robinson, B G; Church, W B; Benn, D E; Dwight, T; Clifton-Bligh, R J

    2015-06-01

    Mitochondrial dysfunction, due to mutations of the gene encoding succinate dehydrogenase (SDH), has been implicated in the development of adrenal phaeochromocytomas, sympathetic and parasympathetic paragangliomas, renal cell carcinomas, gastrointestinal stromal tumours and more recently pituitary tumours. Underlying mechanisms behind germline SDH subunit B (SDHB) mutations and their associated risk of disease are not clear. To investigate genotype-phenotype correlation of SDH subunit B (SDHB) variants, a homology model for human SDH was developed from a crystallographic structure. SDHB mutations were mapped, and biochemical effects of these mutations were predicted in silico. Results of structural modelling indicated that many mutations within SDHB are predicted to cause either failure of functional SDHB expression (p.Arg27*, p.Arg90*, c.88delC and c.311delAinsGG), or disruption of the electron path (p.Cys101Tyr, p.Pro197Arg and p.Arg242His). GFP-tagged WT SDHB and mutant SDHB constructs were transfected (HEK293) to determine biological outcomes of these mutants in vitro. According to in silico predictions, specific SDHB mutations resulted in impaired mitochondrial localisation and/or SDH enzymatic activity. These results indicated strong genotype-functional correlation for SDHB variants. This study reveals new insights into the effects of SDHB mutations and the power of structural modelling in predicting biological consequences. We predict that our functional assessment of SDHB mutations will serve to better define specific consequences for SDH activity as well as to provide a much needed assay to distinguish pathogenic mutations from benign variants. PMID:25972245

  6. MAPPING OF SUCCINATE DEHYDROGENASE LOSSES IN 2258 EPITHELIAL NEOPLASMS

    PubMed Central

    Miettinen, Markku; Sarlomo-Rikala, Maarit; Cue, Peter Mc.; Czapiewski, Piotr; Langfor, Renata; Waloszczyk, Piotr; Wazny, Krzysztof; Biernat, Wojciech; Lasota, Jerzy; Wang, Zengfeng

    2013-01-01

    Losses in the succinate dehydrogenase (SDH) complex characterize 20–30% of extra-adrenal paragangliomas and 7–8% of gastric GISTs, and rare renal cell carcinomas. This loss is reflected as lack of the normally ubiquitous immunohistochemical expression of the SDH subunit B (SDHB). In paragangliomas, SDHB loss correlates with homozygous loss of any of the SDH subunits, typically by loss-of-function mutations. The occurrence of SDHB losses in other epithelial malignancies is unknown. In this study, we immunohistochemically examined 2258 epithelial, mostly malignant neoplasms including common carcinomas of all sites. Among renal cell carcinomas, SDHB loss was observed in 4 of 711 cases (0.6%) including a patient with an SDHB-deficient GIST. Histologically the SDHB-negative renal carcinomas varied. There was one clear cell carcinoma with a high nuclear grade, one papillary carcinoma type 2, one unclassified carcinoma with a glandular pattern, and one oncocytoid low-grade carcinoma as previously described for SDHB-negative renal carcinoma. None of these patients was known to have paragangliomas or had loss of SDHA expression in the tumor. Three of these patients had metastases at presentation (2 in the adrenal, one in the retroperitoneal lymph nodes). There were no cases with SDHB-loss among 64 renal oncocytomas. SDHB-losses were not seen in other carcinomas, except in one prostatic adenocarcinoma (1/57), one lymphoepithelial carcinoma of the stomach, and one (1/40) seminoma. Based on this study, SDHB-losses occur in 0.6% of renal cell carcinomas and extremely rarely in other carcinomas. Some of these renal carcinomas may be clinically aggressive. The clinical significance and molecular genetics of these SDHB-negative tumors requires further study. PMID:23531856

  7. Urinary Bladder Paragangliomas: Analysis of Succinate Dehydrogenase and Outcome.

    PubMed

    Gupta, Sounak; Zhang, Jun; Rivera, Michael; Erickson, Lori A

    2016-09-01

    Paragangliomas of the urinary bladder can arise sporadically or as a part of hereditary syndromes including those with underlying mutations in the succinate dehydrogenase (SDH) genes, which serve as tumor suppressors. SDH deficiency can be screened for by absence of immunohistochemical detection of SDHB. In this study of 11 cases, clinical follow-up was available for 9/11 cases. The cases were reviewed and graded based on the grading system for adrenal pheochromocytomas and paragangliomas (GAPP) criteria. Immunohistochemistry was performed for Ki67 and SDHB. Proliferative index was calculated by quantification of Ki67-positive cells at hot spots. The medical record was accessed for documentation of germline SDH mutations. Urinary bladder paragangliomas had a female predilection (8/11 cases), and 5/11 cases exhibited metastatic behavior. Patients with metastatic disease tended to be younger (mean age 43 vs 49 years), have larger lesions (5.8 vs 1.5 cm), and presented with catecholamine excess (4/4 vs 2/6 patients with non-metastatic lesions). Patients with metastatic disease had a higher mean Ki67 proliferation rate (4.9 vs 1.3 %) and GAPP score (mean of 5.8 vs 3.8) (p = 0.01). IHC for SDHB expression revealed loss of expression in 2/6 cases of non-metastatic paragangliomas compared to 4/5 patients with metastatic paragangliomas. Interestingly, of these four patients, two had a documented mutation of SDHB, one patient had a SDHC mutation, and another patient had a history of familial disease without mutation analysis being performed. Our study, suggests that SDH loss was suggestive of metastatic behavior in addition to younger age at diagnosis, larger tumor size, and higher Ki67 proliferation rate and catecholamine type. PMID:27262318

  8. Pairwise polymer blends for oral drug delivery.

    PubMed

    Marks, Joyann A; Wegiel, Lindsay A; Taylor, Lynne S; Edgar, Kevin J

    2014-09-01

    Blends of polymers with complementary properties hold promise for addressing the diverse, demanding polymer performance requirements in amorphous solid dispersions (ASDs), but we lack comprehensive property understanding for blends of important ASD polymers. Herein, we prepare pairwise blends of commercially available polymers polyvinylpyrrolidone (PVP), the cationic acrylate copolymer Eudragit 100 (E100), hydroxypropyl methylcellulose acetate succinate (HPMCAS), carboxymethyl cellulose acetate butyrate (CMCAB), hydroxypropyl methylcellulose (HPMC), and the new derivative cellulose acetate adipate propionate (CAAdP). This study identifies miscible binary blends that may find use, for example, in ASDs for solubility and bioavailability enhancement of poorly water-soluble drugs. Differential scanning calorimetry, FTIR spectroscopy, and film clarity were used to determine blend miscibility. Several polymer combinations including HPMCAS/PVP, HPMC/CMCAB, and PVP/HPMC appear to be miscible in all proportions. In contrast, blends of E100/PVP and E100/HPMC showed a miscibility gap. Combinations of water-soluble and hydrophobic polymers like these may permit effective balancing of ASD performance criteria such as release rate and polymer-drug interaction to prevent nucleation and crystal growth of poorly soluble drugs. Miscible polymer combinations described herein will enable further study of their drug delivery capabilities, and provide a potentially valuable set of ASD formulation tools. PMID:24823790

  9. 21 CFR 522.533 - Deslorelin acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Deslorelin acetate. (a) Specifications. Each implant contains 2.1 milligrams deslorelin acetate. (b) Sponsor.... One implant per mare. (ii) Indications for use. For inducing ovulation within 48 hours in...

  10. Carbon-isotopic analysis of dissolved acetate

    NASA Technical Reports Server (NTRS)

    Gelwicks, J. T.; Hayes, J. M.

    1990-01-01

    Heating of dried, acetate-containing solids together with oxalic acid dihydrate conveniently releases acetic acid for purification by gas chromatography. For determination of the carbon-isotopic composition of total acetate, the acetate-containing zone of the chromatographic effluent can be routed directly to a combustion furnace coupled to a vacuum system allowing recovery, purification, and packaging of CO2 for mass-spectrometric analysis. For analysis of methyl carbon, acetic acid can be cryogenically trapped from the chromatographic effluent, then transferred to a tube containing excess NaOH. The tube is evacuated, sealed, and heated to 500 degrees C to produce methane by pyrolysis of sodium acetate. Subsequent combustion of the methane allows determination of the 13C content at the methyl position in the parent acetate. With typical blanks, the standard deviation of single analyses is less than 0.4% for acetate samples larger than 5 micromoles. A full treatment of uncertainties is outlined.

  11. Ozone decomposition in aqueous acetate solutions

    SciTech Connect

    Sehested, K.; Holcman, J.; Bjergbakke, E.; Hart, E.J.

    1987-01-01

    The acetate radical ion reacts with ozone with a rate constant of k = (1.5 +/- 0.5) x 10Z dmT mol s . The products from this reaction are CO2, HCHO, and O2 . By subsequent reaction of the peroxy radical with ozone the acetate radical ion is regenerated through the OH radical. A chain decomposition of ozone takes place. It terminates when the acetate radical ion reacts with oxygen forming the unreactive peroxy acetate radical. The chain is rather short as oxygen is developed, as a result of the ozone consumption. The inhibiting effect of acetate on the ozone decay is rationalized by OH scavenging by acetate and successive reaction of the acetate radical ion with oxygen. Some products from the bimolecular disappearance of the peroxy acetate radicals, however, react further with ozone, reducing the effectiveness of the stabilization.

  12. The oxidative activities of membrane vesicles from Bacillus caldolyticus. Energy-dependence of succinate oxidation.

    PubMed

    Dawson, A G; Chappell, J B

    1978-02-15

    1. The properties of membrane vesicles from the extreme thermophile Bacillus caldolyticus were investigated. 2. Vesicles prepared by exposure of spheroplasts to ultrasound contained cytochromes a, b and c, and at 50 degrees C they rapidly oxidized NADH and ascorbate in the presence of tetramethyl-p-phenylenediamine. Succinate and l-malate were oxidized more slowly, and dl-lactate, l-alanine and glycerol 1-phosphate were not oxidized. 3. In the absence of proton-conducting uncouplers the oxidation of NADH was accompanied by a net translocation of H(+) into the vesicles. Hydrolysis of ATP by a dicyclohexylcarbodi-imide-sensitive adenosine triphosphatase was accompanied by a similarly directed net translocation of H(+). 4. Uncouplers (carbonyl cyanide p-trifluoromethoxyphenylhydrazone or valinomycin plus NH(4) (+)) prevented net H(+) translocation but stimulated ATP hydrolysis, NADH oxidation and ascorbate oxidation. The last result suggested an energy-conserving site in the respiratory chain between cytochrome c and oxygen. 5. Under anaerobic conditions the reduction of cytochrome b by ascorbate (with tetramethyl-p-phenylenediamine) was stimulated by ATP hydrolysis, indicating an energy-conserving site between cytochrome b and cytochrome c. However, no reduction of NAD(+) supported by oxidation of succinate, malate or ascorbate occurred, neither did it with these substrates in the presence of ATP under anaerobic conditions, suggesting that there was no energy-conserving site between NADH and cytochrome b. 6. Succinate oxidation, in contrast with that of NADH and ascorbate, was strongly inhibited by uncouplers and stimulated by ATP hydrolysis. These effects were not observed when phenazine methosulphate, which transfers electrons from succinate dehydrogenase directly to oxygen, was present. It was concluded that in these vesicles the oxidation of succinate was energy-dependent and that the reoxidation of reduced succinate dehydrogenase was dependent on the outward

  13. 21 CFR 184.1721 - Sodium acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium acetate. 184.1721 Section 184.1721 Food and....1721 Sodium acetate. (a) Sodium acetate (C2H3O2Na, CAS Reg. No. 127-09-3 or C2H3O2Na·3H2O, CAS Reg. No. 6131-90-4) is the sodium salt of acetic acid and occurs naturally in plant and animal tissues....

  14. The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy

    PubMed Central

    Hu, Liang; Feng, Yu; Wang, Song; Zhang, Wei-yan; Yin, Ning; Mo, Xu-Ming

    2016-01-01

    Background Pulmonary arterial hypertension is characterized by increased pressure overload that leads to right ventricular hypertrophy (RVH). GPR91 is a formerly orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate; however, its role in RVH remains unknown. Methods and Results We investigated the role of succinate-GPR91 signaling in a pulmonary arterial banding (PAB) model of RVH induced by pressure overload in SD rats. GPR91 was shown to be located in cardiomyocytes. In the sham and PAB rats, succinate treatment further aggravated RVH, up-regulated RVH-associated genes and increased p-Akt/t-Akt levels in vivo. In vitro, succinate treatment up-regulated the levels of the hypertrophic gene marker anp and p-Akt/t-Akt in cardiomyocytes. All these effects were inhibited by the PI3K antagonist wortmannin both in vivo and in vitro. Finally, we noted that the GPR91-PI3K/Akt axis was also up-regulated compared to that in human RVH. Conclusions Our findings indicate that succinate-GPR91 signaling may be involved in RVH via PI3K/Akt signaling in vivo and in vitro. Therefore, GPR91 may be a novel therapeutic target for treating pressure overload-induced RVH. PMID:26824665

  15. Glycerol as a substrate for aerobic succinate production in minimal medium with Corynebacterium glutamicum

    PubMed Central

    Litsanov, Boris; Brocker, Melanie; Bott, Michael

    2013-01-01

    Corynebacterium glutamicum, an established microbial cell factory for the biotechnological production of amino acids, was recently genetically engineered for aerobic succinate production from glucose in minimal medium. In this work, the corresponding strains were transformed with plasmid pVWEx1-glpFKD coding for glycerol utilization genes from Escherichia coli. This plasmid had previously been shown to allow growth of C. glutamicum with glycerol as sole carbon source. The resulting strains were tested in minimal medium for aerobic succinate production from glycerol, which is a by-product in biodiesel synthesis. The best strain BL-1/pVWEx1-glpFKD formed 79 mM (9.3 g l−1) succinate from 375 mM glycerol, representing 42% of the maximal theoretical yield under aerobic conditions. A specific succinate production rate of 1.55 mmol g−1 (cdw) h−1 and a volumetric productivity of 3.59 mM h−1 were obtained, the latter value representing the highest one currently described in literature. The results demonstrate that metabolically engineered strains of C. glutamicum are well suited for aerobic succinate production from glycerol. PMID:22513227

  16. Doxofylline and methylprednisolone sodium succinate are stable and compatible under normal injection conditions.

    PubMed

    Xu, Fan; Feng, Enfu; Su, Li; Xu, Guili

    2013-03-01

    To assess the physical compatibility and chemical stability of doxofylline with methylprednisolone sodium succinate in 0.9% sodium chloride or 5% dextrose injection for intravenous infusion. Twenty mL doxofylline solution (0.74 mg/mL) and 1 mL methylprednisolone sodium succinate solution (0.15 mg/mL) were added into 250 mL polyolefin bags containing 5% dextrose injection or 0.9% sodium chloride injection, and stored for 24 h at 20-25(°)C. Chemical compatibility was measured with high-performance liquid chromatography (HPLC), and physical compatibility was determined visually. The results showed that samples were clear and colorless when viewed in normal fluorescent room light. The pH value exhibited little change. The particulate content of > 25 μm was low and within the specification limit. The particulate content of > 10 μm decreased over time and was similar to the control solution. Analysis of chemical stability revealed that doxofylline is stable with methylprednisolone sodium succinate for up to 24 h, and the degradation of methylprednisolone sodium succinate is unrelated to doxofylline, but is closely related to the pH value of the solution. Doxofylline and methylprednisolone sodium succinate did not affect the stability of each other. PMID:23455194

  17. Pretreatment of spent sulphite liquor via ultrafiltration and nanofiltration for bio-based succinic acid production.

    PubMed

    Pateraki, Chrysanthi; Ladakis, Dimitrios; Stragier, Lutgart; Verstraete, Willy; Kookos, Ioannis; Papanikolaou, Seraphim; Koutinas, Apostolis

    2016-09-10

    Ultrafiltration and nanofiltration of spent sulphite liquor (SSL) has been employed to evaluate the simultaneous production of lignosulphonates and bio-based succinic acid using the bacterial strains Actinobacillus succinogenes and Basfia succiniciproducens. Ultrafiltration with membranes of 10, 5 and 3kDa molecular weight cut-off results in significant losses of lignosulphonates (26-50%) in the permeate stream, while nanofiltration using membrane with 500Da molecular weight cut-off results in high retention yields of lignosulphonates (95.6%) in the retentate stream. Fed-batch bioreactor cultures using permeates from ultrafiltrated SSL resulted in similar succinic acid concentration (27.5g/L) and productivity (0.4g/L/h) by both strains. When permeates from nanofiltrated SSL were used, the strain B. succiniciproducens showed the highest succinic acid concentration (33.8g/L), yield (0.58g per g of consumed sugars) and productivity (0.48g/L/h). The nanofiltration of 1t of thick spent sulphite liquor could lead to the production of 306.3kg of lignosulphonates and 52.7kg of succinic acid, whereas the ultrafiltration of 1t of thick spent sulphite liquor using a 3kDa membrane could result in the production of 237kg of lignosulphonates and 71.8kg of succinic acid when B. succiniproducens is used in both cases. PMID:27374402

  18. Statistical optimization for succinic acid production from E. coli in a cost-effective medium.

    PubMed

    Agarwal, Lata; Isar, Jasmine; Dutt, Kakoli; Saxena, Rajendra K

    2007-08-01

    Response surface methodology (RSM) was employed for optimization of medium components and cultural parameters in cost effective cane molasses based medium for attaining high yield of succinic acid. The important factors obtained by "one-variable-at-a-time-approach" (cane molasses, corn steep liquor, sodium carbonate, and inoculum density) were further optimized by RSM. The optimum values of the parameters obtained through RSM (cane molasses 12.5%, corn steep liquor 7.5%, and sodium carbonate 25 mM) led to almost double yield of succinic acid (15.2 g/l in 36 h) as against "one-variable-at-a-time-approach" (7.1 g/l in 36 h) in 500-ml anaerobic bottles containing 300-ml cane molasses based medium. Subsequently, in 10-l bioreactor succinic acid production from Escherichia coli was further improved to 26.2 g/l in 30 h under conditions optimized through RSM. This fermentation-derived succinic acid will definitely help in replacing existing environmentally hazardous and cost-intensive chemical methods for the production of succinic acid. PMID:18025577

  19. Kinetics of the Methanogenic Fermentation of Acetate

    PubMed Central

    Fukuzaki, Satoshi; Nishio, Naomichi; Nagai, Shiro

    1990-01-01

    Inhibition of the fermentation of acetate to methane and carbon dioxide by acetate was analyzed with an acetate-acclimatized sludge and with Methanosarcina barkeri Fusaro under mesophilic conditions. A second-order substrate inhibition model, qch4 = qmS/[Ks + S + (S2/Ki)], where S was the concentration of undissociated acetic acid, not ionized acetic acid, could be applicable in both cases. The analysis resulted in substrate saturation constants, Ks, of 4.0 μM for the acclimatized sludge and 104 μM for M. barkeri. The threshold concentrations of undissociated acetic acid when no further acetate utilization was observed were 0.078 μM (pH 7.50) for the acclimatized sludge and 4.43 μM (pH 7.45) for M. barkeri. These kinetic results suggested that the concentration of undissociated acetic acid became a key factor governing the actual threshold acetate concentration for acetate utilization and that the acclimatized sludge in which Methanothrix spp. appeared dominant could utilize acetate better and survive at a lower concentration of undissociated acetic acid than could M. barkeri. Images PMID:16348323

  20. 21 CFR 522.2476 - Trenbolone acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... days. (A) 140 milligrams (mg) trenbolone acetate (one implant consisting of 7 pellets, each pellet containing 20 mg trenbolone acetate) per implant dose. (B) 140 mg trenbolone acetate (one implant consisting... 29 mg tylosin tartrate) per implant dose. (ii) Indications for use. For improved feed...

  1. 21 CFR 522.2476 - Trenbolone acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... days. (A) 140 milligrams (mg) trenbolone acetate (one implant consisting of 7 pellets, each pellet containing 20 mg trenbolone acetate) per implant dose. (B) 140 mg trenbolone acetate (one implant consisting... 29 mg tylosin tartrate) per implant dose. (ii) Indications for use. For improved feed...

  2. 21 CFR 522.2476 - Trenbolone acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... days. (A) 140 milligrams (mg) trenbolone acetate (one implant consisting of 7 pellets, each pellet containing 20 mg trenbolone acetate) per implant dose. (B) 140 mg trenbolone acetate (one implant consisting... 29 mg tylosin tartrate) per implant dose. (ii) Indications for use. For improved feed...

  3. 21 CFR 522.2476 - Trenbolone acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... days. (A) 140 milligrams (mg) trenbolone acetate (one implant consisting of 7 pellets, each pellet containing 20 mg trenbolone acetate) per implant dose. (B) 140 mg trenbolone acetate (one implant consisting... 29 mg tylosin tartrate) per implant dose. (ii) Indications for use. For improved feed...

  4. 21 CFR 582.6185 - Calcium acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium acetate. 582.6185 Section 582.6185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium acetate. (a) Product. Calcium acetate. (b) Conditions of use. This substance is...

  5. 21 CFR 582.1005 - Acetic acid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Acetic acid. 582.1005 Section 582.1005 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1005 Acetic acid. (a) Product. Acetic acid. (b) Conditions of use. This substance is...

  6. 21 CFR 184.1005 - Acetic acid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Acetic acid. 184.1005 Section 184.1005 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT FOOD....1005 Acetic acid. (a) Acetic acid (C2H4O2, CAS Reg. No. 64-19-7) is known as ethanoic acid. It...

  7. 21 CFR 582.1005 - Acetic acid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Acetic acid. 582.1005 Section 582.1005 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1005 Acetic acid. (a) Product. Acetic acid. (b) Conditions of use. This substance is...

  8. 21 CFR 582.1005 - Acetic acid.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Acetic acid. 582.1005 Section 582.1005 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1005 Acetic acid. (a) Product. Acetic acid. (b) Conditions of use. This substance is...

  9. 21 CFR 582.1005 - Acetic acid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Acetic acid. 582.1005 Section 582.1005 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1005 Acetic acid. (a) Product. Acetic acid. (b) Conditions of use. This substance is...

  10. 21 CFR 582.1005 - Acetic acid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Acetic acid. 582.1005 Section 582.1005 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1005 Acetic acid. (a) Product. Acetic acid. (b) Conditions of use. This substance is...

  11. 21 CFR 582.1721 - Sodium acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium acetate. 582.1721 Section 582.1721 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1721 Sodium acetate. (a) Product. Sodium acetate. (b) Conditions of use. This substance is...

  12. 21 CFR 582.1721 - Sodium acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Sodium acetate. 582.1721 Section 582.1721 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1721 Sodium acetate. (a) Product. Sodium acetate. (b) Conditions of use. This substance is...

  13. 21 CFR 582.1721 - Sodium acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium acetate. 582.1721 Section 582.1721 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1721 Sodium acetate. (a) Product. Sodium acetate. (b) Conditions of use. This substance is...

  14. 21 CFR 582.1721 - Sodium acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sodium acetate. 582.1721 Section 582.1721 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1721 Sodium acetate. (a) Product. Sodium acetate. (b) Conditions of use. This substance is...

  15. 21 CFR 582.1721 - Sodium acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium acetate. 582.1721 Section 582.1721 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1721 Sodium acetate. (a) Product. Sodium acetate. (b) Conditions of use. This substance is...

  16. Acet-oxy-γ-valerolactone.

    PubMed

    Tristram, Cameron; Gainsford, Graeme J; Hinkley, Simon

    2013-06-01

    Levulinyl cellulose esters have been produced as an effective renewable binder for architectural coatings. The title compound, C7H10O4 (systematic name: 2-methyl-5-oxo-tetra-hydro-furan-2-yl acetate), assigned as the esterifying species, was isolated and crystallized to confirm the structure. In the crystal, the mol-ecules pack in layers parallel to (102) utilizing weak C-H⋯O inter-actions. PMID:23795112

  17. Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process

    PubMed Central

    Ha, Eun-Sol; Kim, Jeong-Soo; Baek, In-hwan; Yoo, Jin-Wook; Jung, Yunjin; Moon, Hyung Ryong; Kim, Min-Soo

    2015-01-01

    In the present study, solid dispersion nanoparticles with a hydrophilic polymer and surfactant were developed using the supercritical antisolvent (SAS) process to improve the dissolution and oral absorption of megestrol acetate. The physicochemical properties of the megestrol acetate solid dispersion nanoparticles were characterized using scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and a particle-size analyzer. The dissolution and oral bioavailability of the nanoparticles were also evaluated in rats. The mean particle size of all solid dispersion nanoparticles that were prepared was <500 nm. Powder X-ray diffraction and differential scanning calorimetry measurements showed that megestrol acetate was present in an amorphous or molecular dispersion state within the solid dispersion nanoparticles. Hydroxypropylmethyl cellulose (HPMC) solid dispersion nanoparticles significantly increased the maximum dissolution when compared with polyvinylpyrrolidone K30 solid dispersion nanoparticles. The extent and rate of dissolution of megestrol acetate increased after the addition of a surfactant into the HPMC solid dispersion nanoparticles. The most effective surfactant was Ryoto sugar ester L1695, followed by D-α-tocopheryl polyethylene glycol 1000 succinate. In this study, the solid dispersion nanoparticles with a drug:HPMC:Ryoto sugar ester L1695 ratio of 1:2:1 showed >95% rapid dissolution within 30 minutes, in addition to good oral bioavailability, with approximately 4.0- and 5.5-fold higher area under the curve (0–24 hours) and maximum concentration, respectively, than raw megestrol acetate powder. These results suggest that the preparation of megestrol acetate solid dispersion nanoparticles using the supercritical antisolvent process is a promising approach to improve the dissolution and absorption properties of megestrol acetate. PMID:26345723

  18. Crystallization and immersion freezing ability of oxalic and succinic acid in multicomponent aqueous organic aerosol particles

    NASA Astrophysics Data System (ADS)

    Wagner, Robert; Höhler, Kristina; Möhler, Ottmar; Saathoff, Harald; Schnaiter, Martin

    2015-04-01

    This study reports on heterogeneous ice nucleation efficiency of immersed oxalic and succinic acid crystals in the temperature range from 245 to 215 K, as investigated with expansion cooling experiments using suspended particles. In contrast to previous laboratory work with emulsified solution droplets where the precipitation of solid inclusions required a preceding freezing/evaporation cycle, we show that immersed solids readily form by homogeneous crystallization within aqueous solution droplets of multicomponent organic mixtures, which have noneutonic compositions with an excess of oxalic or succinic acid. Whereas succinic acid crystals did not act as heterogeneous ice nuclei, immersion freezing by oxalic acid dihydrate crystals led to a reduction of the ice saturation ratio at freezing onset by 0.066-0.072 compared to homogeneous freezing, which is by a factor of 2 higher than previously reported laboratory data. These observations emphasize the importance of oxalic acid in heterogeneous ice nucleation.

  19. Solid/liquid phase diagram of the ammonium sulfate/succinic acid/water system.

    PubMed

    Pearson, Christian S; Beyer, Keith D

    2015-05-14

    We have studied the low-temperature phase diagram and water activities of the ammonium sulfate/succinic acid/water system using differential scanning calorimetry and infrared spectroscopy of thin films. Using the results from our experiments, we have mapped the solid/liquid ternary phase diagram, determined the water activities based on the freezing point depression, and determined the ice/succinic acid phase boundary as well as the ternary eutectic composition and temperature. We also compared our results to the predictions of the extended AIM aerosol thermodynamics model (E-AIM) and found good agreement for the ice melting points in the ice primary phase field of this system; however, differences were found with respect to succinic acid solubility temperatures. We also compared the results of this study with those of previous studies that we have published on ammonium sulfate/dicarboxylic acid/water systems. PMID:25431860

  20. dl-. cap alpha. -tocopheryl succinate enhances the effect of. gamma. -irradiation on neuroblastoma cells in culture

    SciTech Connect

    Sarri, A.; Prasad, K.N.

    1984-01-01

    The effect of dl-..cap alpha..-tocopheryl (vitamin E) succinate in modifying the radiation response of mouse neuroblastoma (NBP/sub 2/) and mouse fibroblast (L-cells) cells in culture was studied on the criterion of growth inhibition (due to cell death and inhibition of cell division). Results show that vitamin E succinate markedly enhanced the effect of /sub 60/CO-..gamma..-irradiation on NB cells, but it did not significantly modify the effect of irradiation on mouse fibroblasts. Sodium succinate plus ethanol (0.25% final concentration) did not modify the radiation response of NB cells or fibroblasts. Butylated hydroxyanisole, a lipid soluble antioxidant, also enhanced the effect of irradiation on NB cells, indicating that the effect of vitamin E in modifying the radiation response may be mediated, in part, by antioxidation mechanisms.

  1. Starch sodium dodecenyl succinate prepared by one-step extrusion and its properties.

    PubMed

    Tian, Yaoqi; Zhang, Xiwen; Sun, Binhua; Jin, Zhengyu; Wu, Shengjun

    2015-11-20

    One-step extrusion was developed to prepare starch sodium dodecenyl succinate (SSDS). Effects of screwing speed, reaction temperature, moisture content, sodium hydroxide amount (as catalyst), and dodecenly succinic anhydride (DDSA) amount on the degree of substitution (DS) were investigated. Optimum conditions were determined and found to be as follows: screwing speed, 110rpm; temperature, 120°C; moisture content, 30%; sodium hydroxide amount, 0.5%; DDSA amount, 3%. Under these conditions, the DS of SSDS was 0.014%, and the reaction efficiency was 78%. The structure of SSDS prepared by one-step extrusion was partially characterised. Infrared absorption spectra showed peaks of ester bond and carbonyl group at 1707 and 1564cm(-1), respectively, indicating that dodecenyl succinic groups were introduced into starch molecule backbone by esterification agent. X-ray diffraction analysis showed that compared with native starch, the particle morphology of SSDS prepared by extrusion became irregular, and its crystallinity was partially destroyed. PMID:26344259

  2. Maintenance of Homeostasis in the Aging Hypothalamus: The Central and Peripheral Roles of Succinate

    PubMed Central

    Chen, Thomas T.; Maevsky, Eugene I.; Uchitel, Mikhail L.

    2015-01-01

    Aging is the phenotype resulting from accumulation of genetic, cellular, and molecular damages. Many factors have been identified as either the cause or consequence of age-related decline in functions and repair mechanisms. The hypothalamus is the source and a target of many of these factors and hormones responsible for the overall homeostasis in the body. With advanced age, the sensitivity of the hypothalamus to various feedback signals begins to decline. In recent years, several aging-related genes have been identified and their signaling pathways elucidated. These gene products include mTOR, IKK-β/NF-κB complex, and HIF-1α, an important cellular survival signal. All of these activators/modulators of the aging process have also been identified in the hypothalamus and shown to play crucial roles in nutrient sensing, metabolic regulation, energy balance, reproductive function, and stress adaptation. This illustrates the central role of the hypothalamus in aging. Inside the mitochondria, succinate is one of the most prominent intermediates of the Krebs cycle. Succinate oxidation in mitochondria provides the most powerful energy output per unit time. Extra-mitochondrial succinate triggers a host of succinate receptor (SUCN1 or GPR91)-mediated signaling pathways in many peripheral tissues including the hypothalamus. One of the actions of succinate is to stabilize the hypoxia and cellular stress conditions by inducing the transcriptional regulator HIF-1α. Through these actions, it is hypothesized that succinate has the potential to restore the gradual but significant loss in functions associated with cellular senescence and systemic aging. PMID:25699017

  3. [The mechanism of acetate assimilation in purple nonsulfur bacteria lacking the glyoxylate pathway: enzymes of the citramalate cycle in Rhodobacter sphaeroides].

    PubMed

    Filatova, L V; Berg, I A; Krasil'nikova, E N; Ivanovskiĭ, R N

    2005-01-01

    The mechanism of acetate assimilation by the purple nonsulfur bacterium Rhodobacter sphaeroides, which lacks the glyoxylate shortcut, has been studied. In a previous work, proceeding from data on acetate assimilation by Rba. sphaeroides cell suspensions, a suggestion was made regarding the operation, in this bacterium, of the citramalate cycle. This cycle was earlier found in Rhodospirillum rubrum in the form of an anaplerotic reaction sequence that operates during growth on acetate instead of the glyoxylate shortcut, which is not present in the latter bacterium. The present work considers the enzymes responsible for acetate assimilation in Rba. sphaeroides. It is shown that this bacterium possesses the key enzymes of the citramalate cycle: citramalate synthase, which catalyzes condensation of acetyl-CoA and pyruvate and, as a result, forms citramalate, and 3-methylmalyl-CoA lyase, which catalyzes the cleavage of 3-methylmalyl-CoA to glyoxylate and propionyl-CoA. The regeneration of pyruvate, which is the acetyl-CoA acceptor in the citramalate cycle, involves propionyl-CoA and occurs via the following reaction sequence: propionyl-CoA (+ CO2) --> methylmalonyl-CoA --> succinyl-CoA --> succinate --> fumarate --> malate --> oxalacetate (- CO2) --> phosphoenolpyruvate --> pyruvate. The independence of the cell growth and the acetate assimilation of CO2 is due to the accumulation of CO2/HCO3- (released during acetate assimilation) in cells to a level sufficient for the effective operation of propionyl-CoA carboxylase. PMID:16119844

  4. The possible role of hydrothermal vents in chemical evolution: Succinic acid radiolysis and thermolysis

    NASA Astrophysics Data System (ADS)

    Cruz-Castañeda, J.; Colín-García, M.; Negrón-Mendoza, A.

    2014-07-01

    In this research, the behavior under a high radiation field or high temperature of succinic acid, a dicarboxylic acid clue in metabolic routes, is studied. For this purpose, the molecule was irradiated with gamma rays in oxygen-free aqueous solutions, and the thermal decomposition was studied in a static system at temperatures up to 90 °C, simulating a white hydrothermal vent. Our results indicate that a succinic acid is a relatively stable compound under irradiation. The gamma radiolysis yields carbon dioxide and di- and tricarboxylic acids such as malonic, carboxysuccinic, and citric acids. The main products obtained by the thermal treatment were CO2 and propionic acid.

  5. The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase

    PubMed Central

    Sciacovelli, Marco; Guzzo, Giulia; Morello, Virginia; Frezza, Christian; Zheng, Liang; Nannini, Nazarena; Calabrese, Fiorella; Laudiero, Gabriella; Esposito, Franca; Landriscina, Matteo; Defilippi, Paola; Bernardi, Paolo; Rasola, Andrea

    2013-01-01

    Summary We report that the mitochondrial chaperone TRAP1, which is induced in most tumor types, is required for neoplastic growth and confers transforming potential to noncancerous cells. TRAP1 binds to and inhibits succinate dehydrogenase (SDH), the complex II of the respiratory chain. The respiratory downregulation elicited by TRAP1 interaction with SDH promotes tumorigenesis by priming the succinate-dependent stabilization of the proneoplastic transcription factor HIF1α independently of hypoxic conditions. These findings provide a mechanistic clue to explain the switch to aerobic glycolysis of tumors and identify TRAP1 as a promising antineoplastic target. PMID:23747254

  6. A lipid membrane intercalating conjugated oligoelectrolyte enables electrode driven succinate production in Shewanella

    SciTech Connect

    Thomas, AW; Garner, LE; Nevin, KP; Woodard, TL; Franks, AE; Lovley, DR; Sumner, JJ; Sund, CJ; Bazan, GC

    2013-06-01

    An amphiphilic conjugated oligoelectrolyte (COE) that spontaneously intercalates into lipid membranes enables Shewanella oneidensis to use a graphite electrode as the sole electron donor for succinate production. Current consumed in a poised electrochemical system by Shewanella with micromolar concentrations of COE correlates well with the succinate produced via fumarate reduction as determined by HPLC analysis. Confocal microscopy confirms incorporation of the COE into the microbes on the electrode surface. This work presents a unique strategy to induce favorable bio-electronic interactions for the production of reduced microbial metabolites.

  7. Poly(butylene succinate) and its copolymers: research, development and industrialization.

    PubMed

    Xu, Jun; Guo, Bao-Hua

    2010-11-01

    Poly(butylene succinate) (PBS) and its copolymers are a family of biodegradable polymers with excellent biodegradability, thermoplastic processability and balanced mechanical properties. In this article, production of the monomers succinic acid and butanediol, synthesis, processing and properties of PBS and its copolymers are reviewed. The physical properties and biodegradation rate of PBS materials can be varied in a wide range through copolymerization with different types and various contents of monomers. PBS has a wide temperature window for thermoplastic processing, which makes the resin suitable for extrusion, injection molding, thermoforming and film blowing. Finally, we summarized industrialization and applications of PBS. PMID:21058317

  8. Indications for /sup 99m/technetium dimercapto-succinic acid scan in children

    SciTech Connect

    Gordon, I.

    1987-03-01

    The /sup 99m/technetium dimercapto-succinic acid scan provides an image of functional renal parenchyma. This static scan has specific indications and cannot be used simply in place of a /sup 99m/technetium diethylenetriaminepentaacetic acid scan. The major clinical indications for this investigation are the detection and/or evaluation of a renal scar, the small or absent kidney, an occult duplex system, certain renal masses, systemic hypertension or suspected vasculitis. The physiology of the /sup 99m/technetium dimercapto-succinic acid scan is reviewed briefly.

  9. Acetohydroxy acid synthase I is required for isoleucine and valine biosynthesis by Salmonella typhimurium LT2 during growth on acetate or long-chain fatty acids.

    PubMed

    Dailey, F E; Cronan, J E; Maloy, S R

    1987-02-01

    Salmonella typhimurium LT2 normally expresses two acetohydroxy acid synthases (AHAS I and AHAS II). The function of AHAS I in this organism was unclear, since AHAS I-deficient (ilvBN) mutants of LT2 grew well on glucose or succinate minimal media, whereas AHAS II-deficient (ilvGM) mutants requried isoleucine for normal growth on glucose minimal media. We report that AHAS I-deficient mutants of S. typhimurium required isoleucine and valine for growth on acetate or oleate minimal media, whereas AHAS II-deficient mutants were able to grow on these media without isoleucine supplementation. PMID:3542980

  10. [Determination of succinic acid in desvenlafaxine succinate by high performance ion-exclusion chromatography and high performance ion-exchange chromatography].

    PubMed

    Zong, Yanping; Li, Jinghua; Sun, Wei; Liu, Guixia; Lu, Jinghua; Shan, Guangzhi

    2016-02-01

    New methods were developed for the determination of succinic acid in desvenlafaxine succinate (DVS) by high performance ion-exclusion chromatography (HPIEC) and high performance ion-exchange chromatography (HPIC). HPIEC and HPIC methods were used separately to determinate the succinic acid in DVS. With HPIEC, the sample was diluted with 2. 50 x 10(-3) mol/L sulfuric acid solution and filtrated by 0. 22 µm polyether sulfone filter membrane, and then analyzed by HPIEC directly without any further pretreatment. The analytical column was Phenomenex Rezex ROA-organic Acid H+(8%) (300 mmx7. 8 mm). The mobile phase was 2. 50x10(-3) mol/L sulfuric acid solution at the flow rate of 0. 5 mL/min. The column temperature was set at 40 °C, and the detection wavelength was 210 nm. The injection volume was 10 KL. The assay was quantified by external standard method. With HPIC, the sample was diluted with ultrapure water and filtrated by 0. 22 µm polyether sulfone filter membrane, and then analyzed by HPIC directly without any further pretreatment. The analytical column was Dionex IonPac AS11-HC (250 mm x 4 mm) with a guard column IonPacAG11-HC (50 mm x 4 mm). Isocratic KOH elute generator was used at the flow rate of 1. 0 mL/min. The detection was performed by a Dionex suppressed (DIONEX AERS 500 4-mm) conductivity detector. The injection volume was 10 µL. The content computation was performed with peak area external reference method. The results of HPIEC method for succinic acid were 28. 8%, 28. 9% and 28. 9%, while the results of HPIEC method were 28. 2%, 28. 6% and 28. 6%. The results of HPIEC and HPIC methods were not significantly different. The two methods can both be used to determine the contents of succinic acid in DVS. The surveillance analytical method should be chosen according to the situation. PMID:27382725

  11. Volatility of Organic Aerosol: Evaporation of Ammonium Sulfate/Succinic Acid Aqueous Solution Droplets

    PubMed Central

    2013-01-01

    Condensation and evaporation modify the properties and effects of atmospheric aerosol particles. We studied the evaporation of aqueous succinic acid and succinic acid/ammonium sulfate droplets to obtain insights on the effect of ammonium sulfate on the gas/particle partitioning of atmospheric organic acids. Droplet evaporation in a laminar flow tube was measured in a Tandem Differential Mobility Analyzer setup. A wide range of droplet compositions was investigated, and for some of the experiments the composition was tracked using an Aerosol Mass Spectrometer. The measured evaporation was compared to model predictions where the ammonium sulfate was assumed not to directly affect succinic acid evaporation. The model captured the evaporation rates for droplets with large organic content but overestimated the droplet size change when the molar concentration of succinic acid was similar to or lower than that of ammonium sulfate, suggesting that ammonium sulfate enhances the partitioning of dicarboxylic acids to aqueous particles more than currently expected from simple mixture thermodynamics. If extrapolated to the real atmosphere, these results imply enhanced partitioning of secondary organic compounds to particulate phase in environments dominated by inorganic aerosol. PMID:24107221

  12. [Mutating Escherichia coli by atmospheric and room temperature plasmas for succinic acid production from xylose].

    PubMed

    Wan, Qing; Cao, Weijia; Zhang, Changqing; Liu, Rongming; Liang, Liya; Chen, Kequan; Ma, Jiangfeng; Jiang, Min

    2013-11-01

    Escherichia coli AFP111 is a spontaneous mutant with mutations in the glucose specific phosphotransferase system (ptsG) in NZN111 (delta pflAB deltaldhA). In AFP111, conversion of xylose to succinic acid generates 1.67 molecule of ATP per xylose. However, the strain needs 2.67 molecule ATP for xylose metabolism. Therefore, AFP111 cannot use xylose due to insufficient ATP under anaerobic condition. Through an atmospheric and room temperature plasma (ARTP) jet, we got a mutant strain named DC111 that could use xylose under anaerobic condition in M9 medium to produce succinic acid. After 72 h, DC111 consumed 10.52 g/L xylose to produce 6.46 g/L succinic acid, and the yield was 0.78 mol/mol. Furthermore, the reaction catalyzed by the ATP-generating PEP-carboxykinase (PCK) was enhanced. The specific activity of PCK was 19.33-fold higher in DC111 than that in AFP111, which made the strain have enough ATP to converse xylose to succinic acid. PMID:24701836

  13. Succinic Acid as a Byproduct in a Corn-based Ethanol Biorefinery

    SciTech Connect

    MBI International

    2007-12-31

    MBI endeavored to develop a process for succinic acid production suitable for integration into a corn-based ethanol biorefinery. The project investigated the fermentative production of succinic acid using byproducts of corn mill operations. The fermentation process was attuned to include raw starch, endosperm, as the sugar source. A clean-not-sterile process was established to treat the endosperm and release the monomeric sugars. We developed the fermentation process to utilize a byproduct of corn ethanol fermentations, thin stillage, as the source of complex nitrogen and vitamin components needed to support succinic acid production in A. succinogenes. Further supplementations were eliminated without lowering titers and yields and a productivity above 0.6 g l-1 hr-1was achieved. Strain development was accomplished through generation of a recombinant strain that increased yields of succinic acid production. Isolation of additional strains with improved features was also pursued and frozen stocks were prepared from enriched, characterized cultures. Two recovery processes were evaluated at pilot scale and data obtained was incorporated into our economic analyses.

  14. 21 CFR 172.765 - Succistearin (stearoyl propylene glycol hydrogen succinate).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Succistearin (stearoyl propylene glycol hydrogen succinate). 172.765 Section 172.765 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN...

  15. 21 CFR 172.765 - Succistearin (stearoyl propylene glycol hydrogen succinate).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Succistearin (stearoyl propylene glycol hydrogen succinate). 172.765 Section 172.765 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION...

  16. 21 CFR 172.765 - Succistearin (stearoyl propylene glycol hydrogen succinate).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Succistearin (stearoyl propylene glycol hydrogen succinate). 172.765 Section 172.765 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN...

  17. 21 CFR 172.765 - Succistearin (stearoyl propylene glycol hydrogen succinate).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Succistearin (stearoyl propylene glycol hydrogen succinate). 172.765 Section 172.765 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN...

  18. Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation.

    PubMed

    Lampropoulou, Vicky; Sergushichev, Alexey; Bambouskova, Monika; Nair, Sharmila; Vincent, Emma E; Loginicheva, Ekaterina; Cervantes-Barragan, Luisa; Ma, Xiucui; Huang, Stanley Ching-Cheng; Griss, Takla; Weinheimer, Carla J; Khader, Shabaana; Randolph, Gwendalyn J; Pearce, Edward J; Jones, Russell G; Diwan, Abhinav; Diamond, Michael S; Artyomov, Maxim N

    2016-07-12

    Remodeling of the tricarboxylic acid (TCA) cycle is a metabolic adaptation accompanying inflammatory macrophage activation. During this process, endogenous metabolites can adopt regulatory roles that govern specific aspects of inflammatory response, as recently shown for succinate, which regulates the pro-inflammatory IL-1β-HIF-1α axis. Itaconate is one of the most highly induced metabolites in activated macrophages, yet its functional significance remains unknown. Here, we show that itaconate modulates macrophage metabolism and effector functions by inhibiting succinate dehydrogenase-mediated oxidation of succinate. Through this action, itaconate exerts anti-inflammatory effects when administered in vitro and in vivo during macrophage activation and ischemia-reperfusion injury. Using newly generated Irg1(-/-) mice, which lack the ability to produce itaconate, we show that endogenous itaconate regulates succinate levels and function, mitochondrial respiration, and inflammatory cytokine production during macrophage activation. These studies highlight itaconate as a major physiological regulator of the global metabolic rewiring and effector functions of inflammatory macrophages. PMID:27374498

  19. Formation and stability of Vitamin E enriched nanoemulsions stabilized by Octenyl Succinic Anhydride modified starch

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin E (VE) is highly susceptible to autoxidation; therefore, it requires systems to encapsulate and protect it from autoxidation.In this study,we developed VE delivery systems, which were stabilized by Capsul® (MS), a starch modified with octenyl succinic anhydride. Influences of interfacial ten...

  20. Tumor microenvironment promotes dicarboxylic acid carrier-mediated transport of succinate to fuel prostate cancer mitochondria

    PubMed Central

    Zhunussova, Aigul; Sen, Bhaswati; Friedman, Leah; Tuleukhanov, Sultan; Brooks, Ari D; Sensenig, Richard; Orynbayeva, Zulfiya

    2015-01-01

    Prostate cancer cells reprogram their metabolism, so that they support their elevated oxidative phosphorylation and promote a cancer friendly microenvironment. This work aimed to explore the mechanisms that cancer cells employ for fueling themselves with energy rich metabolites available in interstitial fluids. The mitochondria oxidative phosphorylation in metastatic prostate cancer DU145 cells and normal prostate epithelial PrEC cells were studied by high-resolution respirometry. An important finding was that prostate cancer cells at acidic pH 6.8 are capable of consuming exogenous succinate, while physiological pH 7.4 was not favorable for this process. Using specific inhibitors, it was demonstrated that succinate is transported in cancer cells by the mechanism of plasma membrane Na+-dependent dycarboxylic acid transporter NaDC3 (SLC13A3 gene). Although the level of expression of SLC13A3 was not significantly altered when maintaining cells in the medium with lower pH, the respirometric activity of cells under acidic condition was elevated in the presence of succinate. In contrast, normal prostate cells while expressing NaDC3 mRNA do not produce NaDC3 protein. The mechanism of succinate influx via NaDC3 in metastatic prostate cancer cells could yield a novel target for anti-cancer therapy and has the potential to be used for imaging-based diagnostics to detect non-glycolytic tumors. PMID:26175936

  1. 76 FR 59141 - Determination That LOXITANE (Loxapine Succinate) Capsules and Three Other Drug Products Were Not...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Determination That LOXITANE (Loxapine Succinate) Capsules and Three Other Drug Products Were Not Withdrawn From Sale for Reasons of Safety or...

  2. Nano-encapsulation of coenzyme Q10 using octenyl succinic anhydride modified starch

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Octenyl succinic anhydride modified starch (OSA-ST) was used to encapsulate Coenzyme Q10 (CoQ10). CoQ10 was dissolved in rice bran oil (RBO), and incorporated into an aqueous OSA-ST solution. High pressure homogenization (HPH) of the mixture was conducted at 170 MPa for 5-6 cycles. The resulting ...

  3. Integration of Succinic Acid Production in a Dry Mill Ethanol Facility

    SciTech Connect

    2006-08-01

    This project seeks to address both issues for a dry mill ethanol biorefinery by lowering the cost of sugars with the development of an advanced pretreatment process, improving the economics of succinic acid (SA), and developing a model of an ethanol dry mill to evaluate the impact of adding different products and processes to a dry mill.

  4. Inhibition of Salmonella Typhimurium by Anaerobic Cecal Bacteria in Media Supplemented with Lactate and Succinate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ability of anaerobic cecal microflora of broilers to inhibit growth of Salmonella Typhimurium in media supplemented with lactate and succinate was examined. Cecal cultures were prepared by collecting ceca of processed broilers from a commercial processing facility, inoculating broth media with 1...

  5. Nucleation kinetics of urea succinic acid –ferroelectric single crystal

    SciTech Connect

    Dhivya, R.; Vizhi, R. Ezhil E-mail: revizhi@gmail.com; Babu, D. Rajan

    2015-06-24

    Single crystals of Urea Succinic Acid (USA) were grown by slow cooling technique. The crystalline system was confirmed by powder X-ray diffraction. The metastable zonewidth were carried out for various temperatures i.e., 35°, 40°, 45° and 50°C. The induction period is experimentally determined and various nucleation parameters have been estimated.

  6. A complete industrial system for economical succinic acid production by Actinobacillus succinogenes.

    PubMed

    Li, Jian; Zheng, Xiao-Yu; Fang, Xiao-Jiang; Liu, Shu-Wen; Chen, Ke-Quan; Jiang, Min; Wei, Ping; Ouyang, Ping-Kai

    2011-05-01

    An industrial fermentation system using lignocellulosic hydrolysate, waste yeast hydrolysate, and mixed alkali to achieve high-yield, economical succinic acid production by Actinobacillus succinogenes was developed. Lignocellulosic hydrolysate and waste yeast hydrolysate were used efficiently as carbon sources and nitrogen source instead of the expensive glucose and yeast extract. Moreover, as a novel method for regulating pH mixed alkalis (Mg(OH)(2) and NaOH) were first used to replace the expensive MgCO(3) for succinic acid production. Using the three aforementioned substitutions, the total fermentation cost decreased by 55.9%, and 56.4 g/L succinic acid with yield of 0.73 g/g was obtained, which are almost the same production level as fermentation with glucose, yeast extract and MgCO(3). Therefore, the cheap carbon and nitrogen sources, as well as the mixed alkaline neutralize could be efficiently used instead of expensive composition for industrial succinic acid production. PMID:21470857

  7. Bilayer mucoadhesive microparticles for the delivery of metoprolol succinate: Formulation and evaluation.

    PubMed

    Kumar, Krishan; Dhawan, Neha; Sharma, Harshita; Patwal, Pramod S; Vaidya, Shubha; Vaidya, Bhuvaneshwar

    2015-01-01

    Metoprolol succinate is a very potent drug for the treatment of hypertension but suffers from poor bioavailability due to its erratic absorption in lower GI tract. Therefore, in the present study, it was hypothesized that by formulating mucoadhesive particles, the residence time in the GIT and release of drug may be prolonged that will enhance the bioavailability of metoprolol succinate. Metoprolol succinate loaded chitosan microparticles were prepared by ionic gelation method. The optimized microparticles were coated with sodium alginate to form a layer over chitosan microparticles to increase the mucoadhesive strength and to release the drug in controlled manner. Coated and uncoated microparticles were evaluated for particle size, zeta potential, morphology, entrapment efficiency, drug loading and in vitro drug release. The coated microparticles showed comparatively less drug release in the 0.1 N HCl while sustained release in PBS (pH 6.8) as compared to uncoated microparticles. The in vivo study on albino rats demonstrated an increase in bioavailability of the coated microparticles as compared to marketed formulation. From the study it can be concluded that alginate coated chitosan microparticles could be a useful carrier for the oral delivery of metoprolol succinate. PMID:24579883

  8. Understanding Palladium Acetate from a User Perspective.

    PubMed

    Carole, William A; Colacot, Thomas J

    2016-06-01

    The behavior of palladium acetate is reviewed with respect to its synthesis, characterization, structure (in both solution and solid state), and activation pathways. In addition, comparisons of catalytic activities between pure palladium acetate and two common byproducts, Pd3 (OAc)5 (NO2 ) and polymeric [Pd(OAc)2 ]n , typically present in commercially available material are reviewed. Hence, this minireview serves as a concise guide for the users of palladium acetate from both academia and industry. PMID:27125630

  9. 21 CFR 184.1005 - Acetic acid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Acetic acid. 184.1005 Section 184.1005 Food and... Substances Affirmed as GRAS § 184.1005 Acetic acid. (a) Acetic acid (C2H4O2, CAS Reg. No. 64-19-7) is known as ethanoic acid. It occurs naturally in plant and animal tissues. It is produced by fermentation...

  10. 21 CFR 184.1005 - Acetic acid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Acetic acid. 184.1005 Section 184.1005 Food and... Substances Affirmed as GRAS § 184.1005 Acetic acid. (a) Acetic acid (C2H4O2, CAS Reg. No. 64-19-7) is known as ethanoic acid. It occurs naturally in plant and animal tissues. It is produced by fermentation...

  11. 21 CFR 184.1721 - Sodium acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... sodium sulfate and sodium bicarbonate. (b) The ingredient meets the specifications of the Food Chemicals... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium acetate. 184.1721 Section 184.1721 Food and... Substances Affirmed as GRAS § 184.1721 Sodium acetate. (a) Sodium acetate (C2H3O2Na, CAS Reg. No. 127-09-3...

  12. 21 CFR 184.1721 - Sodium acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... sodium sulfate and sodium bicarbonate. (b) The ingredient meets the specifications of the Food Chemicals... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium acetate. 184.1721 Section 184.1721 Food and... Substances Affirmed as GRAS § 184.1721 Sodium acetate. (a) Sodium acetate (C2H3O2Na, CAS Reg. No. 127-09-3...

  13. 21 CFR 184.1721 - Sodium acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... sodium sulfate and sodium bicarbonate. (b) The ingredient meets the specifications of the Food Chemicals... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium acetate. 184.1721 Section 184.1721 Food and... Substances Affirmed as GRAS § 184.1721 Sodium acetate. (a) Sodium acetate (C2H3O2Na, CAS Reg. No. 127-09-3...

  14. Metabolite Profiling Reveals YihU as a Novel Hydroxybutyrate Dehydrogenase for Alternative Succinic Semialdehyde Metabolism in Escherichia coli*

    PubMed Central

    Saito, Natsumi; Robert, Martin; Kochi, Hayataro; Matsuo, Goh; Kakazu, Yuji; Soga, Tomoyoshi; Tomita, Masaru

    2009-01-01

    The search for novel enzymes and enzymatic activities is important to map out all metabolic activities and reveal cellular metabolic processes in a more exhaustive manner. Here we present biochemical and physiological evidence for the function of the uncharacterized protein YihU in Escherichia coli using metabolite profiling by capillary electrophoresis time-of-flight mass spectrometry. To detect enzymatic activity and simultaneously identify possible substrates and products of the putative enzyme, we profiled a complex mixture of metabolites in the presence or absence of YihU. In this manner, succinic semialdehyde was identified as a substrate for YihU. The purified YihU protein catalyzed in vitro the NADH-dependent reduction of succinic semialdehyde to γ-hydroxybutyrate. Moreover, a yihU deletion mutant displayed reduced tolerance to the cytotoxic effects of exogenous addition of succinic semialdehyde. Profiling of intracellular metabolites following treatment of E. coli with succinic semialdehyde supports the existence of a YihU-catalyzed reduction of succinic semialdehyde to γ-hydroxybutyrate in addition to its known oxidation to succinate and through the tricarboxylic acid cycle. These findings suggest that YihU is a novel γ-hydroxybutyrate dehydrogenase involved in the metabolism of succinic semialdehyde, and other potentially toxic intermediates that may accumulate under stress conditions in E. coli. PMID:19372223

  15. Comparing pyridoxine and doxylamine succinate-pyridoxine HCl for nausea and vomiting of pregnancy: A matched, controlled cohort study.

    PubMed

    Pope, Eliza; Maltepe, Caroline; Koren, Gideon

    2015-07-01

    Nausea and vomiting of pregnancy (NVP) is a common gestational condition. This is the first study to compare the use of vitamin B6 (pyridoxine) versus Diclectin (doxylamine succinate-pyridoxine HCl) for NVP symptoms. Participants were pregnant women with NVP who used either pyridoxine or doxylamine succinate-pyridoxine HCl for ≥4 days prior to calling the Motherisk NVP Helpline. Women receiving pyridoxine only (n = 80) were matched to a woman taking doxylamine succinate-pyridoxine HCl only (n = 80), accounting for potential confounders and baseline level of NVP, measured by the Pregnancy Unique Quantification of Emesis (PUQE) score. Change in NVP severity after a week of therapy with either pyridoxine or doxylamine succinate-pyridoxine HCl was quantified using the PUQE-24 scale, which describes NVP symptoms 24 hours prior to their call. Doxylamine succinate-pyridoxine HCl use found a significant reduction in PUQE score, compared with pyridoxine (+0.5 versus -0.2, P < .05; negative denotes worsening). This association was especially prominent in women with more severe symptoms, where doxylamine succinate-pyridoxine HCl use saw a mean improvement of 2.6 versus 0.4 with pyridoxine (P < .05). As well, doxylamine succinate-pyridoxine HCl use was associated with fewer women experiencing moderate to severe scores after a week of treatment, compared with the pyridoxine group (7 versus 17, P < .05), despite similar baseline PUQE scores. PMID:25663469

  16. Positron scattering from vinyl acetate

    NASA Astrophysics Data System (ADS)

    Chiari, L.; Zecca, A.; Blanco, F.; García, G.; Brunger, M. J.

    2014-09-01

    Using a Beer-Lambert attenuation approach, we report measured total cross sections (TCSs) for positron scattering from vinyl acetate (C4H6O2) in the incident positron energy range 0.15-50 eV. In addition, we also report an independent atom model with screening corrected additivity rule computation results for the TCSs, differential and integral elastic cross sections, the positronium formation cross section and inelastic integral cross sections. The energy range of these calculations is 1-1000 eV. While there is a reasonable qualitative correspondence between measurement and calculation for the TCSs, in terms of the energy dependence of those cross sections, the theory was found to be a factor of ˜2 larger in magnitude at the lower energies, even after the measured data were corrected for the forward angle scattering effect.

  17. Extractive fermentation of acetic acid

    SciTech Connect

    Busche, R.M.

    1991-12-31

    In this technoeconomic evaluation of the manufacture of acetic acid by fermentation, the use of the bacterium: Acetobacter suboxydans from the old vinegar process was compared with expected performance of the newer Clostridium thermoaceticum bacterium. Both systems were projected to operate as immobilized cells in a continuous, fluidized bed bioreactor, using solvent extraction to recover the product. Acetobacter metabolizes ethanol aerobically to produce acid at 100 g/L in a low pH medium. This ensures that the product is in the form of a concentrated extractable free acid, rather than as an unextractable salt. Unfortunately, yields from glucose by way of the ethanol fermentation are poor, but near the biological limits of the organisms involved. Conversely, C. thermoaceticum is a thermophilic anaerobe that operates at high fermentation rates on glucose at neutral pH to produce acetate salts directly in substantially quantitative yields. However, it is severely inhibited by product, which restricts concentration to a dilute 20 g/L. An improved Acetobacter system operating with recycled cells at 50 g/L appears capable of producing acid at $0.38/lb, as compared with a $0.29/lb price for synthetic acid. However, this system has only a limited margin for process improvement. The present Clostridium system cannot compete, since the required selling price would be $0.42/lb. However, if the organism could be adapted to tolerate higher product concentrations at acid pH, selling price could be reduced to $0.22/lb, or about 80% of the price of synthetic acid.

  18. Real Time Molecular Imaging of TCA Cycle Metabolism in vivo By Hyperpolarized 1-13C Diethyl Succinate

    PubMed Central

    Zacharias, Niki M.; Chan, Henry R.; Sailasuta, Napapon; Ross, Brian D.

    2011-01-01

    The Krebs tricarboxylic acid cycle (TCA) is central to metabolic energy production and is known to be altered in many disease states. Real time molecular imaging of TCA cycle in vivo will be important in understanding the metabolic basis of several diseases. Positron emission tomography (PET) using FDG-glucose (2-[18F]fluoro-2-deoxy-D-glucose) is already being used as a metabolic imaging agent in clinics. However, FDG-glucose does not reveal anything past glucose uptake and phosphorylation. We have developed a new metabolic imaging agent, hyperpolarized diethyl 1-13C 2,3-d2 succinate, that allows for real time in vivo imaging and spectroscopy of the TCA cycle. Diethyl succinate can be hyperpolarized using parahydrogen induced polarization (PHIP) in an aqueous solution with signal enhancement of 5000 compared to Boltzmann polarization. 13C magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) were achieved in vivo seconds after injection of 10 to 20 μmol of hyperpolarized diethyl succinate into normal mice. The downstream metabolites of hyperpolarized diethyl succinate were identified in vivo as malate, succinate, fumarate and aspartate. The metabolism of diethyl succinate was altered after exposing the animal to 3-nitropropionate, a known irreversible inhibitor of succinate dehydrogenase. Based on our results, hyperpolarized diethyl succinate allows for in real time in vivo MRI and MRS with a high signal to noise ratio and with visualization of multiple steps of the TCA cycle. Hyperpolarization of diethyl succinate and its in vivo applications may reveal an entirely new regime wherein the local status of TCA cycle metabolism is interrogated on the time scale of seconds to minutes with unprecedented chemical specificity and MR sensitivity. PMID:22146049

  19. Studies on the mechanism of synthesis of ethyl acetate in Kluyveromyces marxianus DSM 5422.

    PubMed

    Löser, Christian; Urit, Thanet; Keil, Peter; Bley, Thomas

    2015-02-01

    Kluyveromyces marxianus converts whey-borne sugar into ethyl acetate, an environmentally friendly solvent with many applications. K. marxianus DSM 5422 presumably synthesizes ethyl acetate from acetyl-SCoA. Iron limitation as a trigger for this synthesis is explained by a diminished aconitase and succinate dehydrogenase activity (both enzymes depend on iron) causing diversion of acetyl-SCoA from the tricarboxic acid cycle to ester synthesis. Copper limitation as another trigger for ester synthesis in this yeast refers to involvement of the electron transport chain (all ETC complexes depend on iron and complex IV requires copper). This hypothesis was checked by using several ETC inhibitors. Malonate was ineffective but carboxin partially inhibited complex II and initiated ester synthesis. Antimycin A and cyanide as complexes III and IV inhibitors initiated ester synthesis only at moderate levels while higher concentrations disrupted all respiration and caused ethanol formation. A restricted supply of oxygen (the terminal electron acceptor) also initiated some ester synthesis but primarily forced ethanol production. A switch from aerobic to anaerobic conditions nearly stopped ester synthesis and induced ethanol formation. Iron-limited ester formation was compared with anaerobic ethanol production; the ester yield was lower than the ethanol yield but a higher market price, a reduced number of process stages, a faster process, and decreased expenses for product recovery by stripping favor biotechnological ester production. PMID:25487884

  20. Emission characteristics of carboxylates in PM2.5 from incense burning with the effect of light on acetate

    NASA Astrophysics Data System (ADS)

    Kuo, Su-Ching; Tsai, Ying I.; Sopajaree, Khajornsak

    2016-08-01

    Incense burning produces potentially harmful particulate matter. In this study we investigated the emissions of PM2.5 and gaseous acetic acid from four brands of traditional incense; Liao and Shang Lao Shan (SLS), sold in Taiwan, and Thai Yellow (Thai Y) and Thai Black (Thai B), sold in Thailand. Additionally, photochemical reactions of PM2.5 carboxylates emitted from incense burning were studied via a simulated light experiment. The average PM2.5 mass emission factor of each incense type was inversely correlated with the ash production of that incense. The Thailand incense carboxylate emissions were markedly higher than the Taiwan incense. Acetate accounted for 87.46% of total carboxylate emissions, with acetate emitted from the Thailand incense 1.26 times higher than from the Taiwan incense. Phthalate was detected in the PM2.5, indicating the presence of plasticizer. Concentrations of PM2.5 acetate, formate, pyruvate, glutarate, succinate, fumarate and tartarate were reduced in simulated light (51.5%-97.1% of those under dark), indicating that these seven types of carboxylate are easily photodegradable. In contrast, malonate, maleate, oxalate and phthalate concentrations in light were 1.17-1.84 times higher than in darkness, indicating photochemical reactions contribute to the formation of these species. The formation of the low-molecular weight dicarboxylates oxalate and malonate was most noticeable. Acetic acid, highly irritating to the respiratory system and skin, was present at high levels for all four incense types, as shown by the gaseous acetic acid/PM2.5 acetate ratios of 1.03-3.61. Burning incense indoors can generate high concentrations of PM2.5 acetate that increases the risks of respiratory and contact irritation, particularly when burning the Thailand incense. Moreover, burning incense in poorly ventilated, dimly lit indoor areas (e.g., temples and homes) can markedly increase the risk of irritation because the gaseous acetic acid is not degraded as

  1. 21 CFR 556.380 - Melengestrol acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Melengestrol acetate. 556.380 Section 556.380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Tolerances for Residues of New Animal Drugs § 556.380 Melengestrol acetate. A tolerance of 25 parts...

  2. 21 CFR 556.380 - Melengestrol acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Melengestrol acetate. 556.380 Section 556.380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Tolerances for Residues of New Animal Drugs § 556.380 Melengestrol acetate. A tolerance of 25 parts...

  3. 21 CFR 556.380 - Melengestrol acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Melengestrol acetate. 556.380 Section 556.380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Tolerances for Residues of New Animal Drugs § 556.380 Melengestrol acetate. A tolerance of 25 parts...

  4. 21 CFR 556.380 - Melengestrol acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Melengestrol acetate. 556.380 Section 556.380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Tolerances for Residues of New Animal Drugs § 556.380 Melengestrol acetate. A tolerance of 25 parts...

  5. Manufacturing Ethyl Acetate From Fermentation Ethanol

    NASA Technical Reports Server (NTRS)

    Rohatgi, Naresh K.; Ingham, John D.

    1991-01-01

    Conceptual process uses dilute product of fermentation instead of concentrated ethanol. Low-concentration ethanol, extracted by vacuum from fermentation tank, and acetic acid constitutes feedstock for catalytic reaction. Product of reaction goes through steps that increases ethyl acetate content to 93 percent by weight. To conserve energy, heat exchangers recycle waste heat to preheat process streams at various points.

  6. 21 CFR 173.228 - Ethyl acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the specifications of the Food Chemicals Codex, 1 (Ethyl Acetate; p. 372, 3d Ed., 1981), which are... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethyl acetate. 173.228 Section 173.228 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR...

  7. Combinatorial optimization of CO2 transport and fixation to improve succinate production by promoter engineering.

    PubMed

    Yu, Jun-Han; Zhu, Li-Wen; Xia, Shi-Tao; Li, Hong-Mei; Tang, Ya-Ling; Liang, Xin-Hua; Chen, Tao; Tang, Ya-Jie

    2016-07-01

    To balance the flux of an engineered metabolic pathway to achieve high yield of target product is a major challenge in metabolic engineering. In previous work, the collaborative regulation of CO2 transport and fixation was investigated with co-overexpressing exogenous genes regulating both CO2 transport (sbtA and bicA) and PEP carboxylation (phosphoenolpyruvate (PEP) carboxylase (ppc) and carboxykinase (pck)) under trc promoter in Escherichia coli for succinate biosynthesis. For balancing metabolic flux to maximize succinate titer, a combinatorial optimization strategy to fine-tuning CO2 transport and fixation process was implemented by promoter engineering in this study. Firstly, based on the energy matrix a synthetic promoter library containing 20 rationally designed promoters with strengths ranging from 0.8% to 100% compared with the widely used trc promoter was generated. Evaluations of rfp and cat reporter genes provided evidence that the synthetic promoters were stably and had certain applicability. Secondly, four designed promoters with different strengths were used for combinatorial assembly of single CO2 transport gene (sbtA or bicA) and single CO2 fixation gene (ppc or pck) expression. Three combinations, such as Tang1519 (P4 -bicA + pP19 -pck), Tang1522 (P4 -sbtA + P4 -ppc), Tang1523 (P4 -sbtA + P17 -ppc) with a more than 10% increase in succinate production were screened in bioreactor. Finally, based on the above results, co-expression of the four transport and fixation genes were further investigated. Co-expression of sbtA, bicA, and ppc with weak promoter P4 and pck with strong promoter P19 (AFP111/pT-P4 -bicA-P4 -sbtA + pACYC-P19 -pck-P4 -ppc) provided the best succinate production among all the combinations. The highest succinate production of 89.4 g/L was 37.5% higher than that obtained with empty vector control. This work significantly enhanced succinate production through combinatorial optimization of CO2 transport and fixation

  8. Engineering Escherichia coli for succinate production from hemicellulose via consolidated bioprocessing

    PubMed Central

    2012-01-01

    Background The recalcitrant nature of hemicellulosic materials and the high cost in depolymerization are the primary obstacles preventing the use of xylan as feedstock for fuel and chemical production. Consolidated bioprocessing, incorporating enzyme-generating, biomass-degrading and bioproduct-producing capabilities into a single microorganism, could potentially avoid the cost of the dedicated enzyme generation in the process of xylan utilization. In this study, we engineered Escherichia coli strains capable of exporting three hemicellulases to the broth for the succinate production directly from beechwood xylan. Results Xylanases were extracellular environment-directed by fusing with OsmY. Subsequently, twelve variant OsmY fused endoxylanase-xylosidase combinations were characterized and tested. The combination of XynC-A from Fibrobacter succinogenes S85 and XyloA from Fusarium graminearum which appeared to have optimal enzymatic properties was identified as the best choice for xylan hydrolysis (0.18 ± 0.01 g/l protein in the broth with endoxylanase activity of 12.14 ± 0.34 U/mg protein and xylosidase activity of 92 ± 3 mU/mg protein at 8 h after induction). Further improvements of hemicellulases secretion were investigated by lpp deletion, dsbA overexpression and expression level optimization. With co-expression of α-arabinofuranosidase, the engineered E. coli could hydrolyze beechwood xylan to pentose monosaccharides. The hemicellulolytic capacity was further integrated with a succinate-producing strain to demonstrate the production of succinate directly from xylan without externally supplied hydrolases and any other organic nutrient. The resulting E. coli Z6373 was able to produce 0.37 g/g succinate from xylan anaerobically equivalent to 76% of that from xylan acid hydrolysates. Conclusions This report represents a promising step towards the goal of hemicellulosic chemical production. This engineered E. coli expressing and secreting three hemicellulases

  9. Comments on recently published "L-threonine phthalate" and pure and doped "L-lysinium succinate" crystals

    NASA Astrophysics Data System (ADS)

    Petrosyan, A. M.

    2016-04-01

    It is shown that the recently published papers on "L-threonine phthalate" (Theras et al. (2015) [2]) and pure and doped "L-lysinium succinate" (Kalaivani et al. (2015) [11,16]) misidentified the targeted compounds.

  10. Effect of Na/sup +/ replacement on transport and metabolism of succinate and glutamine in jejunal epithelium

    SciTech Connect

    Mallet, R.T.; Jackson, M.J.; Kelleher, J.K.

    1986-03-01

    Novel radioisotope techniques may be applied to the analysis of metabolism and transport in intact cells. In the present study, rat jejunal epithelium was suspended in media containing five concentrations of glutamine between 0 and 5 mM, either Na/sup +/ or N-methyl-D-glucamine (NMDG/sup +/) as the major cation, and 44 ..mu..M (/sup 14/C)succinate. An increased ratio of steady state /sup 14/CO/sub 2/ production from (1,4-/sup 14/C)succinate versus (2,3-/sup 14/C)succinate indicates enhanced efflux of TCA cycle intermediates to products other than CO/sub 2/, relative to cycle flux. Glutamine dependent increases in succinate CO/sub 2/ ratios plateaued above 0.5mM glutamine, indicating that entry of glutamine-derived carbon into TCA cycle intermediate pools was saturated above physiological plasma glutamine concentrations. Although /sup 14/CO/sub 2/ production from succinate tracers was reduced approximately 95% by Na/sup +/ replacement, succinate CO/sub 2/ ratios were not altered, indicating that succinate uptake was significantly reduced in NMDG/sup +/ medium. /sup 14/C-alanine and /sup 14/C-aspartate accumulation increased with increasing glutamine concentrations in a pattern similar to succinate CO/sub 2/ ratios, indicating that these amino acids were net products of glutamine carbon. Incorporation of /sup 14/C into lactate and alanine demonstrated the presence of an enzymatic pathway for conversion of TCA cycle intermediates to pyruvate.

  11. Effect of diphenylhydantoin on gamma aminobutyric acid (GABA) and succinate activity in rat Purkinje cells.

    PubMed Central

    Hitchcock, E; Gabra-Sanders, T

    1977-01-01

    A study has been made of the effect of diphenylhydantoin (DPH) upon the levels of gamma aminobutyric acid (GABA) and succinic dehydrogenase in rat Purkinje cells. DPH was administered over 26 days in chronic experiments using controls receiving the same injection vehicle without DPH. Animals in this group received daily 1.25 mg/kg body weight, 12.5 mg/kg body weight, and 50 mg/kg body weight DPH. Acute experiments were carried out over the course of not more than four days, three groups of animals receiving 75 mg/kg body weight, 87.5 mg/kg body weight, and 100 mg/kg body weight DPH. No effect upon succinic dehydrogenase could be demonstrated at any dose level. There was a significant progressive loss of GABA with increasing dosage of DPH. Images PMID:903771

  12. Comparative analysis of the anxiolytic effects of 3-hydroxypyridine and succinic acid derivatives.

    PubMed

    Volchegorskii, I A; Miroshnichenko, I Yu; Rassokhina, L M; Faizullin, R M; Malkin, M P; Pryakhina, K E; Kalugina, A V

    2015-04-01

    Threefold administration of 3-hydroxypyridine derivatives emoxipine and mexidol in optimal doses corresponding to the therapeutic dose range for humans produced an anxiolytic effect and stimulated risk behavior in the elevated plus maze test in rats. These effects were most pronounced after injection of 3-hydroxypyridine derivative emoxipine. Combination of 3-hydroxypyridine cation and succinate anion in the mexidol structure led to attenuation of the anxiolytic effect and less pronounced stimulation of the risk behavior. By the anxiolytic effect and induction of risk behavior, emoxipine and mexidol were close to the reference substance amitriptyline. Reamberin, a succinic acid derivative, had no pronounced tranquilizing properties, but risk behavior induction was similar to that produced by mexidol. In contrast to other test agents, the reference substance α-lipoic acid produced anxiogenic effects and suppressed risk behavior. The obtained results suggest that Russian-made 3-hydroxypyridine derivatives emoxipine and mexidol are promising preparations for the treatment of anxiety disorders. PMID:25894772

  13. Ferulenol specifically inhibits succinate ubiquinone reductase at the level of the ubiquinone cycle

    SciTech Connect

    Lahouel, Mesbah; Zini, Roland; Zellagui, Ammar; Rhouati, Salah; Carrupt, Pierre-Alain; Morin, Didier; E-mail: didier.morin@creteil.inserm.fr

    2007-03-30

    The natural compound ferulenol, a sesquiterpene prenylated coumarin derivative, was purified from Ferula vesceritensis and its mitochondrial effects were studied. Ferulenol caused inhibition of oxidative phoshorylation. At low concentrations, ferulenol inhibited ATP synthesis by inhibition of the adenine nucleotide translocase without limitation of mitochondrial respiration. At higher concentrations, ferulenol inhibited oxygen consumption. Ferulenol caused specific inhibition of succinate ubiquinone reductase without altering succinate dehydrogenase activity of the complex II. This inhibition results from a limitation of electron transfers initiated by the reduction of ubiquinone to ubiquinol in the ubiquinone cycle. This original mechanism of action makes ferulenol a useful tool to study the physiological role and the mechanism of electron transfer in the complex II. In addition, these data provide an additional mechanism by which ferulenol may alter cell function and demonstrate that mitochondrial dysfunction is an important determinant in Ferula plant toxicity.

  14. High-Fat Diet Reduces the Formation of Butyrate, but Increases Succinate, Inflammation, Liver Fat and Cholesterol in Rats, while Dietary Fibre Counteracts These Effects

    PubMed Central

    Jakobsdottir, Greta; Xu, Jie; Molin, Göran; Ahrné, Siv; Nyman, Margareta

    2013-01-01

    Introduction Obesity is linked to type 2 diabetes and risk factors associated to the metabolic syndrome. Consumption of dietary fibres has been shown to have positive metabolic health effects, such as by increasing satiety, lowering blood glucose and cholesterol levels. These effects may be associated with short-chain fatty acids (SCFAs), particularly propionic and butyric acids, formed by microbial degradation of dietary fibres in colon, and by their capacity to reduce low-grade inflammation. Objective To investigate whether dietary fibres, giving rise to different SCFAs, would affect metabolic risk markers in low-fat and high-fat diets using a model with conventional rats for 2, 4 and 6 weeks. Material and Methods Conventional rats were administered low-fat or high-fat diets, for 2, 4 or 6 weeks, supplemented with fermentable dietary fibres, giving rise to different SCFA patterns (pectin – acetic acid; guar gum – propionic acid; or a mixture – butyric acid). At the end of each experimental period, liver fat, cholesterol and triglycerides, serum and caecal SCFAs, plasma cholesterol, and inflammatory cytokines were analysed. The caecal microbiota was analysed after 6 weeks. Results and Discussion Fermentable dietary fibre decreased weight gain, liver fat, cholesterol and triglyceride content, and changed the formation of SCFAs. The high-fat diet primarily reduced formation of SCFAs but, after a longer experimental period, the formation of propionic and acetic acids recovered. The concentration of succinic acid in the rats increased in high-fat diets with time, indicating harmful effect of high-fat consumption. The dietary fibre partly counteracted these harmful effects and reduced inflammation. Furthermore, the number of Bacteroides was higher with guar gum, while noticeably that of Akkermansia was highest with the fibre-free diet. PMID:24236183

  15. Structure-barrier property relationship of biodegradable poly(butylene succinate) and poly[(butylene succinate)-co-(butylene adipate)] nanocomposites: influence of the rigid amorphous fraction.

    PubMed

    Charlon, S; Marais, S; Dargent, E; Soulestin, J; Sclavons, M; Follain, N

    2015-11-28

    Composites composed of polyesters, poly(butylene succinate) (PBS) or poly[(butylene succinate)-co-(butylene adipate)] (PBSA), and 5 wt% of montmorillonite (CNa) or organo-modified montmorillonite (C30B) were melt-processed and transformed into films by either compression-molding or extrusion-calendering. XRD, rheological measurements and TEM images clearly indicated that films containing CNa are microcomposites, while nanocomposites were observed for those containing C30B. Using Flash DSC, it was possible, for the first time, not only to measure the heat capacity step at the glass transition of these two materials in their amorphous state, but also to investigate whether the preparation technique influenced the Rigid Amorphous Fraction (RAF) in our PBS- and PBSA-based nanocomposites. In this work, we have successfully shown the correlation between the microstructure of the films and their barrier properties, and especially the role played by the RAF. Indeed, the lowest permeabilities to gases and to water were determined in the films containing the highest RAF in both PBS- and PBSA-based materials. PMID:26489904

  16. Model-aided atpE gene knockout strategy in Escherichia coli for enhanced succinic acid production from glycerol.

    PubMed

    Mienda, Bashir Sajo; Shamsir, Mohd Shahir; Md Illias, Rosli

    2016-08-01

    Succinic acid is an important platform chemical with a variety of applications. Model-guided metabolic engineering strategies in Escherichia coli for strain improvement to increase succinic acid production using glucose and glycerol remain largely unexplored. Herein, we report what are, to our knowledge, the first metabolic knockout of the atpE gene to have increased succinic acid production using both glucose and alternative glycerol carbon sources in E. coli. Guided by a genome-scale metabolic model, we engineered the E. coli host to enhance anaerobic production of succinic acid by deleting the atpE gene, thereby generating additional reducing equivalents by blocking H(+) conduction across the mutant cell membrane. This strategy produced 1.58 and .49 g l(-1) of succinic acid from glycerol and glucose substrate, respectively. This work further elucidates a model-guided and/or system-based metabolic engineering, involving only a single-gene deletion strategy for enhanced succinic acid production in E. coli. PMID:26513379

  17. Actinobacillus succinogenes ATCC 55618 Fermentation Medium Optimization for the Production of Succinic Acid by Response Surface Methodology

    PubMed Central

    Zhu, Li-Wen; Wang, Cheng-Cheng; Liu, Rui-Sang; Li, Hong-Mei; Wan, Duan-Ji; Tang, Ya-Jie

    2012-01-01

    As a potential intermediary feedstock, succinic acid takes an important place in bulk chemical productions. For the first time, a method combining Plackett-Burman design (PBD), steepest ascent method (SA), and Box-Behnken design (BBD) was developed to optimize Actinobacillus succinogenes ATCC 55618 fermentation medium. First, glucose, yeast extract, and MgCO3 were identified to be key medium components by PBD. Second, preliminary optimization was run by SA method to access the optimal region of the key medium components. Finally, the responses, that is, the production of succinic acid, were optimized simultaneously by using BBD, and the optimal concentration was located to be 84.6 g L−1 of glucose, 14.5 g L−1 of yeast extract, and 64.7 g L−1 of MgCO3. Verification experiment indicated that the maximal succinic acid production of 52.7 ± 0.8 g L−1 was obtained under the identified optimal conditions. The result agreed with the predicted value well. Compared with that of the basic medium, the production of succinic acid and yield of succinic acid against glucose were enhanced by 67.3% and 111.1%, respectively. The results obtained in this study may be useful for the industrial commercial production of succinic acid. PMID:23093852

  18. Model-guided metabolic gene knockout of gnd for enhanced succinate production in Escherichia coli from glucose and glycerol substrates.

    PubMed

    Mienda, Bashir Sajo; Shamsir, Mohd Shahir; Illias, Rosli Md

    2016-04-01

    The metabolic role of 6-phosphogluconate dehydrogenase (gnd) under anaerobic conditions with respect to succinate production in Escherichia coli remained largely unspecified. Herein we report what are to our knowledge the first metabolic gene knockout of gnd to have increased succinic acid production using both glucose and glycerol substrates in E. coli. Guided by a genome scale metabolic model, we engineered the E. coli host metabolism to enhance anaerobic production of succinic acid by deleting the gnd gene, considering its location in the boundary of oxidative and non-oxidative pentose phosphate pathway. This strategy induced either the activation of malic enzyme, causing up-regulation of phosphoenolpyruvate carboxylase (ppc) and down regulation of phosphoenolpyruvate carboxykinase (ppck) and/or prevents the decarboxylation of 6 phosphogluconate to increase the pool of glyceraldehyde-3-phosphate (GAP) that is required for the formation of phosphoenolpyruvate (PEP). This approach produced a mutant strain BMS2 with succinic acid production titers of 0.35gl(-1) and 1.40gl(-1) from glucose and glycerol substrates respectively. This work further clearly elucidates and informs other studies that the gnd gene, is a novel deletion target for increasing succinate production in E. coli under anaerobic condition using glucose and glycerol carbon sources. The knowledge gained in this study would help in E. coli and other microbial strains development for increasing succinate production and/or other industrial chemicals. PMID:26878126

  19. Actinobacillus succinogenes ATCC 55618 fermentation medium optimization for the production of succinic acid by response surface methodology.

    PubMed

    Zhu, Li-Wen; Wang, Cheng-Cheng; Liu, Rui-Sang; Li, Hong-Mei; Wan, Duan-Ji; Tang, Ya-Jie

    2012-01-01

    As a potential intermediary feedstock, succinic acid takes an important place in bulk chemical productions. For the first time, a method combining Plackett-Burman design (PBD), steepest ascent method (SA), and Box-Behnken design (BBD) was developed to optimize Actinobacillus succinogenes ATCC 55618 fermentation medium. First, glucose, yeast extract, and MgCO(3) were identified to be key medium components by PBD. Second, preliminary optimization was run by SA method to access the optimal region of the key medium components. Finally, the responses, that is, the production of succinic acid, were optimized simultaneously by using BBD, and the optimal concentration was located to be 84.6 g L(-1) of glucose, 14.5 g L(-1) of yeast extract, and 64.7 g L(-1) of MgCO(3). Verification experiment indicated that the maximal succinic acid production of 52.7 ± 0.8 g L(-1) was obtained under the identified optimal conditions. The result agreed with the predicted value well. Compared with that of the basic medium, the production of succinic acid and yield of succinic acid against glucose were enhanced by 67.3% and 111.1%, respectively. The results obtained in this study may be useful for the industrial commercial production of succinic acid. PMID:23093852

  20. Conversion of levulinate into succinate through catalytic oxidative carbon-carbon bond cleavage with dioxygen.

    PubMed

    Liu, Junxia; Du, Zhongtian; Lu, Tianliang; Xu, Jie

    2013-12-01

    Grand Cleft Oxo: Levulinate, available from biomass, is oxidized into succinate through manganese(III)-catalyzed selective cleavage of CC bonds with molecular oxygen. In addition to levulinate, a wide range of aliphatic methyl ketones also undergo oxidative CC bond cleavage at the carbonyl group. This procedure offers a route to valuable dicarboxylic acids from biomass resources by nonfermentive approaches. PMID:23922234

  1. The H+/O ratio of proton translocation linked to the oxidation of succinate by mitochondria.

    PubMed

    Krab, K; Soos, J; Wikström, M

    1984-12-10

    In a recent communication Lehninger and co-workers (Costa, L.E., Reynaferje, B., and Lehninger, A.L. (1984) J. Biol. Chem. 259, 4802-4811) reported values approaching 8 for the H+/O ratio of vectorial proton ejection from rat liver mitochondria respiring with succinate. Here we present a rigorous analysis of these measurements which reveals that they may significantly overestimate the true H+/O stoicheiometry. PMID:6096164

  2. Marked and variable inhibition by chemical fixation of cytochrome oxidase and succinate dehydrogenase in single motoneurons

    NASA Technical Reports Server (NTRS)

    Chalmers, G. R.; Edgerton, V. R.

    1989-01-01

    The effect of tissue fixation on succinate dehydrogenase and cytochrome oxidase activity in single motoneurons of the rat was demonstrated using a computer image processing system. Inhibition of enzyme activity by chemical fixation was variable, with some motoneurons being affected more than others. It was concluded that quantification of enzymatic activity in chemically fixed tissue provides an imprecise estimate of enzyme activities found in fresh-frozen tissues.

  3. Volatility of NH3 from internally mixed sodium succinate-NH4SO4 particles

    NASA Astrophysics Data System (ADS)

    Wang, Na; Zhang, Yunhong

    2016-04-01

    Contributing the complicacy of atmospheric constituents, aerosol particles may undergo complicated heterogeneous reactions that have profound consequences on their hygroscopic properties and volatility. Ammonia (NH3) is a ubiquitous trace atmospheric gas in the troposphere and has negative effects on human health and climate forcing of ambient aerosols. In addition, atmospheric cycle of NH3 is complex in atmosphere, therefore it necessary to get insights to the complexity of gas-to-aerosol NH3 partitioning, which results in large uncertainties in the sources and distributions of NH3. By using in-situ Fourier transform infrared spectroscopy and attenuated total reflection (FTIR-ATR), we report here the volatility of NH3 from the laboratory generated sodium succinate with ammonium sulfate ((NH4)2SO4) at a 1:1 molar ratio as well as its effect on the hygroscopicity of the mixtures. The loss of the NH4+ peak at 1451cm‑1 and the formation of peaks at 1718 and 1134 cm‑1 due to C = O stretching asymmetric vibration of -COOH and ν3 (SO42‑) stretching of sodium sulfate indicate that sodium succinate reacts with (NH4)2SO4, releasing NH3 and forming succinic acid and sodium sulfate on dehydration process. The formation of less hygroscopic succinic acid and volatility of NH3 in mixtures leads to a significant decrease in the total water content. To the best of our knowledge, this is the first report of the reaction between (NH4)2SO4 and dicarboxylate salts, which may represent an important particle-gas partitioning for ammonia and thus elucidate another underlying ammonia cycle in atmosphere. These results could be helpful to understand the mutual transformation process of dicarboxylic acids and dicarboxylate salts.

  4. Succinate dehydrogenase activity and soma size of motoneurons innervating different portions of the rat tibialis anterior

    NASA Technical Reports Server (NTRS)

    Ishihara, A.; Roy, R. R.; Edgerton, V. R.

    1995-01-01

    The spatial distribution, soma size and oxidative enzyme activity of gamma and alpha motoneurons innervating muscle fibres in the deep (away from the surface of the muscle) and superficial (close to the surface of the muscle) portions of the tibialis anterior in normal rats were determined. The deep portion had a higher percentage of high oxidative fibres than the superficial portion of the muscle. Motoneurons were labelled by retrograde neuronal transport of fluorescent tracers: Fast Blue and Nuclear Yellow were injected into the deep portion and Nuclear Yellow into the superficial portion of the muscle. Therefore, motoneurons innervating the deep portion were identified by both a blue fluorescent cytoplasm and a golden-yellow fluorescent nucleus, while motoneurons innervating the superficial portion were identified by only a golden-yellow fluorescent nucleus. After staining for succinate dehydrogenase activity on the same section used for the identification of the motoneurons, soma size and succinate dehydrogenase activity of the motoneurons were measured. The gamma and alpha motoneurons innervating both the deep and superficial portions were located primarily at L4 and were intermingled within the same region of the dorsolateral portion of the ventral horn in the spinal cord. Mean soma size was similar for either gamma or alpha motoneurons in the two portions of the muscle. The alpha motoneurons innervating the superficial portion had a lower mean succinate dehydrogenase activity than those innervating the deep portion of the muscle. An inverse relationship between soma size and succinate dehydrogenase activity of alpha, but not gamma, motoneurons innervating both the deep and superficial portions was observed. Based on three-dimensional reconstructions within the spinal cord, there were no apparent differences in the spatial distribution of the motoneurons, either gamma or alpha, associated with the deep and superficial compartments of the muscle. The data

  5. Effect of vitamin E succinate on inflammatory cytokines induced by high-intensity interval training

    PubMed Central

    Sarir, Hadi; Emdadifard, Ghodsieh; Farhangfar, Homayoun; TaheriChadorneshin, Hossein

    2015-01-01

    Aim and Scope: The anti-inflammatory effect of vitamin E under moderate exercises has been evaluated. However, the effect of vitamin E succinate, which has more potent anti-inflammatory effect than other isomers of vitamin E has not been evaluated. Therefore, the aim of the present study was to evaluate the effects of vitamin E succinate on tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) production induced by high-intensity interval training (HIIT). Materials and Methods: In the present study, 24 rats were randomly divided into control (C), supplementation (S), HIIT, and HIIT + supplementation (HIIT+S) groups. HIIT training protocol on a treadmill (at a speed of 40–54 m/min) and vitamin E succinate supplementation (60 mg/kg/day) was conducted for 6 weeks. Results: Serum IL-6 in the HIIT group significantly increased compared with the C group (350.42 ± 123.31 pg/mL vs 158.60 ± 41.96 pg/mL; P = 0.002). Also, serum TNF-α concentrations significantly enhanced (718.15 ± 133.42 pg/mL vs 350.87 ± 64.93 pg/mL; P = 0.001) in the HIIT group compared with the C group. Treatment of the training group with vitamin E numerically reduced IL-6 and TNF-α when compared with the HIIT group (217.31 ± 29.21 and 510.23 ± 217.88, respectively, P > 0.05). However, no significant changes were observed in serum TNF-α (P = 0.31) and IL-6 (P = 0.52) concentrations in the HIIT + S group compared with the C group. Conclusion: HIIT-induced IL-6 and TNF-α decreased by administration of Vitamin E succinate. PMID:26958053

  6. Yttrium-succinates coordination polymers: Hydrothermal synthesis, crystal structure and thermal decomposition

    SciTech Connect

    Amghouz, Zakariae; Roces, Laura; Garcia-Granda, Santiago; Garcia, Jose R.; Souhail, Badredine; Mafra, Luis; Shi, Fa-nian; Rocha, Joao

    2009-12-15

    New polymeric yttrium-succinates, Y{sub 2}(C{sub 4}H{sub 4}O{sub 4}){sub 3}(H{sub 2}O){sub 4}.6H{sub 2}O and Y{sub 2}(C{sub 4}H{sub 4}O{sub 4}){sub 3}(H{sub 2}O){sub 2}, have been synthesized, and their structures (solved by single crystal XRD) are compared with that of Y{sub 2}(C{sub 4}H{sub 4}O{sub 4}){sub 3}(H{sub 2}O){sub 2}.H{sub 2}O. Three compounds were obtained as single phases, and their thermal behaviour is described. - Graphical abstract: In the field of coordination polymers or MOF's, few studies report on the polymorphs of Ln(III)-succinic acid. Here, we describe the hydrothermal synthesis and structural characterization of two novel yttrium-succinates coordination polymers, respectively 2D and 3D, Y{sub 2}(C{sub 4}H{sub 4}O{sub 4}){sub 3}(H{sub 2}O){sub 4}.6H{sub 2}O and Y{sub 2}(C{sub 4}H{sub 4}O{sub 4}){sub 3}(H{sub 2}O){sub 2}.

  7. Integrated production of cellulosic bioethanol and succinic acid from industrial hemp in a biorefinery concept.

    PubMed

    Kuglarz, Mariusz; Alvarado-Morales, Merlin; Karakashev, Dimitar; Angelidaki, Irini

    2016-01-01

    The aim of this study was to develop integrated biofuel (cellulosic bioethanol) and biochemical (succinic acid) production from industrial hemp (Cannabis sativa L.) in a biorefinery concept. Two types of pretreatments were studied (dilute-acid and alkaline oxidative method). High cellulose recovery (>95%) as well as significant hemicelluloses solubilization (49-59%) after acid-based method and lignin solubilization (35-41%) after alkaline H2O2 method were registered. Alkaline pretreatment showed to be superior over the acid-based method with respect to the rate of enzymatic hydrolysis and ethanol productivity. With respect to succinic acid production, the highest productivity was obtained after liquid fraction fermentation originated from steam treatment with 1.5% of acid. The mass balance calculations clearly showed that 149kg of EtOH and 115kg of succinic acid can be obtained per 1ton of dry hemp. Results obtained in this study clearly document the potential of industrial hemp for a biorefinery. PMID:26551652

  8. Novel FT-IR Microspectroscopic Census of Simple Starch Granules for Octenyl Succinate Ester Modification

    SciTech Connect

    Bai, Y.; Shi, Y; Wetzel, D

    2009-01-01

    Fourier transform infrared (FT-IR) microspectroscopy was used to investigate reaction homogeneity of octenyl succinic anhydride modification on waxy maize starch and detect uniformity of blends of modified and native starches. For the first time, the level and uniformity of chemical substitution on individual starch granules were analyzed by FT-IR microspectroscopy. More than 100 starch granules of each sample were analyzed one by one by FT-IR microspectroscopy. In comparison to the native starch, modified starch had two additional bands at 1723 and 1563 cm{sup -1}, indicative of ester formation in the modified starch. For the 3% modification level, the degree of substitution (DS) was low (0.019) and the distribution of the ester group was not uniform among starch granules. For the modified starch with DS of 0.073, 99% of individual starch granules had a large carbonyl band area, indicating that most granules were modified to a sufficient extent that the presence of their carbonyl ester classified them individually as being modified. However, the octenyl succinate concentration varied between granules, suggesting that the reaction was not uniform. When modified starch (DS = 0.073) was blended with native starch (3:7, w/w) to achieve a mixture with an average DS of 0.019, FT-IR microspectroscopy was able to detect heterogeneity of octenyl succinate in the blend and determine the ratio of the modified starch to the native starch granules.

  9. [Absorption of Uranium with Tea Oil Tree Sawdust Modified by Succinic Acid].

    PubMed

    Zhang, Xiao-feng; Chen, Di-yun; Peng, Yan; Liu, Yong-sheng; Xiong, Xue-ying

    2015-05-01

    In order to explore how the modification of succinic acid improves the adsorption of tea oil tree sawdust for uranium, the tea oil tree sawdust was modified by succinic acid, after the pretreatments of crushing, screening, alkalization and acidification. Infrared analysis indicated carboxylic acid groups and ester groups were added to the sawdust after modification, and scanning electron microscope demonstrated after modification the appearance of tea oil tree sawdust was transferred from the structure like compact and straight stripped into the structure like loose and wrinkled leaves, which meant modification increased its inner pores. By the static experiments, effects of reaction time between adsorbent and solvent, dosage of adsorbent, temperature, pH value and initial concentration of uranium were investigated. The results showed that after the modification by succinic acid, the absorption rate of tea oil tree sawdust for uranium increased significantly by about 20% in 12.5 mg · L(-1) initial concentration uranium solution. Adsorption equilibrium was achieved within 180 min, and the kinetic data can be well described by the pseudo-second-order kinetic model. The experimental adsorption isotherm followed the Langmuir and Freundlich models. In addition, the maximum adsorption amounts of tea oil tree sawdust after modification calculated from Langmuir equation raised from 21.413 3 to 31.545 7 mg · g(-1) at 35°C and pH 4.0. PMID:26314117

  10. Nano-encapsulation of coenzyme Q10 using octenyl succinic anhydride modified starch.

    PubMed

    Cheuk, Sherwin Y; Shih, Frederick F; Champagne, Elaine T; Daigle, Kim W; Patindol, James A; Mattison, Christopher P; Boue, Stephen M

    2015-05-01

    Octenyl succinic anhydride modified starch (OSA-ST) was used to encapsulate coenzyme Q10 (CoQ10). CoQ10 was dissolved in rice bran oil and incorporated into an aqueous OSA-ST solution. High pressure homogenisation of the mixture was conducted at 170 MPa for 56 cycles. The resulting emulsion had a particle size range of 200-300 nm and the absolute zeta potential varied between 8.4 and 10.6 mV. CoQ10 retention of the emulsion and freeze dried products, determined by a hexane rinse, was 98.2%. Reconstitution of the freeze dried product in Mcllvaine citrate-phosphate buffers with pH values of 3-5 and temperatures at 4 and 25 °C had very little effect on the range and distribution of the nanoparticles' size. The inflection point of the zeta potential and pH plot occurred at the first pKa of succinic acid (pH 4.2), indicating succinate as the main influence over zeta potential. PMID:25529723

  11. Study on oil absorbency of succinic anhydride modified banana cellulose in ionic liquid.

    PubMed

    Shang, Wenting; Sheng, Zhanwu; Shen, Yixiao; Ai, Binling; Zheng, Lili; Yang, Jingsong; Xu, Zhimin

    2016-05-01

    Banana cellulose contained number of hydrophilic hydroxyl groups which were succinylated to be hydrophobic groups with high oil affinity. Succinic anhydride was used to modify banana cellulose in 1-allyl-3-methylimidazolium chloride ionic liquid in this study. The modified banana cellulose had a high oil absorption capacity. The effects of reaction time, temperature, and molar ratio of succinic anhydride to anhydroglucose on the degree of substitution of modified banana cellulose were evaluated. The optimal reaction condition was at a ratio of succinic anhydride and anhydroglucose 6:1 (m:m), reaction time 60min and temperature 90°C. The maximum degree of acylation reaction reached to 0.37. The characterization analysis of the modified banana cellulose was performed using X-ray diffractometer, Fourier transform infrared spectrometer, scanning electron microscopy and thermogravimetry. The oil absorption capacity and kinetics of the modified banana cellulose were evaluated at the modified cellulose dose (0.025-0.3g), initial oil amount (5-30g), and temperature (15-35°C) conditions. The maximum oil absorption capacity was 32.12g/g at the condition of the cellulose dose (0.05g), initial oil amount (25g) and temperature (15°C). The kinetics of oil absorption of the cellulose followed a pseudo-second-order model. The results of this study demonstrated that the modified banana cellulose could be used as an efficient bio-sorbent for oil adsorption. PMID:26877005

  12. Formulation and evaluation of bucco-adhesive tablets of sumatriptan succinate

    PubMed Central

    Prasanna, R Indira; Anitha, P; Chetty, C Madhusudhana

    2011-01-01

    Background: A novel aspiration in treatment of migraine, to provide greater therapeutic effect, overcome the side effects by complex therapeutic regimen and to improve patient compliance upon administering bucco-adhesive tablet formulations of sumatriptan succinate which have not been tested literally. Materials and Methods: This study was designed to develop a bucco-adhesive tablet containing sumatriptan succinate using blends of different bio-adhesive polymeric combinations such as hydroxy propyl methyl cellulose K4M, sodium carboxy methyl cellulose, and Carbopol 934P with a backing layer of ethyl cellulose by a direct compression technique. Tablets were subjected to physico-chemical parameters, swelling index, surface pH, ex vivo bioadhesive force, in vitro drug release, ex vivo drug permeation, and stability in saliva. Results: Good results were obtained in all the evaluated parameters. The drug release of all formulation follows zero-order kinetics by a diffusion mechanism type. Stability studies in human saliva, ex vivo buccal permeation studies by using sheep and porcine buccal mucosa were carried out for the optimized formulation (S4 CP:HPMC 3:1). Conclusion: The developed buccal drug delivery system containing sumatriptan succinate might be the alternative routes available to bypass the first pass metabolism and might be a milestone in the therapy of migraine and among all formulations S4 shows good controlled release results correlated with ex vivo permeation studies. PMID:23071941

  13. Efficient and repeated production of succinic acid by turning sugarcane bagasse into sugar and support.

    PubMed

    Chen, Pengcheng; Tao, Shengtao; Zheng, Pu

    2016-07-01

    Here we reported an endeavor in making full use of sugarcane bagasse for biological production of succinic acid. Through NaOH pre-treatment and multi-enzyme hydrolysis, a reducing sugar solution mainly composed of glucose and xylose was obtained from the sugarcane bagasse. By optimizing portions of cellulase, xylanase, β-glucanase and pectinase in the multi-enzyme "cocktail", the hydrolysis percentage of the total cellulose in pre-treated sugarcane bagasse can be as high as 88.5%. A. succinogenes CCTCC M2012036 was used for converting reducing sugars into succinic acid in a 3-L bioreactor with a sugar-fed strategy to prevent cell growth limitation. Importantly, cells were found to be adaptive on the sugarcane bagasse residue, offering possibilities of repeated batch fermentation and replacement for MgCO3 with soluble NaHCO3 in pH modulation. Three cycles of fermentation without activity loss were realized with the average succinic acid yield and productivity to be 80.5% and 1.65g·L(-1)·h(-1). PMID:27035471

  14. Aqueous Phase Photo-Oxidation of Succinic Acid: Changes in Hygroscopic Properties and Reaction Products

    NASA Astrophysics Data System (ADS)

    Hudson, P. K.; Ninokawa, A.; Hofstra, J.; de Lijser, P.

    2013-12-01

    Atmospheric aerosol particles have been identified as important factors in understanding climate change. The extent to which aerosols affect climate is determined, in part, by hygroscopic properties which can change as a result of atmospheric processing. Dicarboxylic acids, components of atmospheric aerosol, have a wide range of hygroscopic properties and can undergo oxidation and photolysis reactions in the atmosphere. In this study, the hygroscopic properties of succinic acid aerosol, a non-hygroscopic four carbon dicarboxylic acid, were measured with a humidified tandem differential mobility analyzer (HTDMA) and compared to reaction products resulting from the aqueous phase photo-oxidation reaction of hydrogen peroxide and succinic acid. Reaction products were determined and quantified using gas chromatography-flame ionization detection (GC-FID) and GC-mass spectrometry (GC-MS) as a function of hydrogen peroxide:succinic acid concentration ratio and photolysis time. Although reaction products include larger non-hygroscopic dicarboxylic acids (e.g. adipic acid) and smaller hygroscopic dicarboxylic acids (e.g. malonic and oxalic acids), comparison of hygroscopic growth curves to Zdanovskii-Stokes-Robinson (ZSR) predictions suggests that the hygroscopic properties of many of the product mixtures are largely independent of the hygroscopicity of the individual components. This study provides a framework for future investigations to fully understand and predict the role of chemical reactions in altering atmospheric conditions that affect climate.

  15. Modeling conformational redox-switch modulation of human succinic semialdehyde dehydrogenase.

    PubMed

    Tamazian, Gaik; Ho Chang, Jeong; Knyazev, Sergey; Stepanov, Eugene; Kim, Kyung-Jin; Porozov, Yuri

    2015-12-01

    Succinic semialdehyde dehydrogenase (SSADH) converts succinic semialdehyde (SSA) to succinic acid in the mitochondrial matrix and is involved in the metabolism of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). The molecular structure of human SSADH revealed the intrinsic regulatory mechanism--redox-switch modulation--by which large conformational changes are brought about in the catalytic loop through disulfide bonding. The crystal structures revealed two SSADH conformations, and computational modeling of transformation between them can provide substantial insights into detailed dynamic redox modulation. On the basis of these two clear crystal structures, we modeled the conformational motion between these structures in silico. For that purpose, we proposed and used a geometry-based coarse-grained mathematical model of long-range protein motion and the related modeling algorithm. The algorithm is based on solving the special optimization problem, which is similar to the classical Monge-Kantorovich mass transportation problem. The modeled transformation was supported by another morphing method based on a completely different framework. The result of the modeling facilitates better interpretation and understanding of the SSADH biological role. PMID:26422261

  16. Co-regulation of mitochondrial respiration by proline dehydrogenase/oxidase and succinate.

    PubMed

    Hancock, Chad N; Liu, Wei; Alvord, W Gregory; Phang, James M

    2016-03-01

    Proline dehydrogenase/oxidase (PRODH/POX) is a mitochondrial protein critical to multiple stress pathways. Because of the roles of PRODH/POX in signaling, and its shared localization to the mitochondrial inner membrane with the electron transport chain (ETC), we investigated whether there was a direct relationship between PRODH/POX and regulation of the ETC. We found that PRODH/POX binds directly to CoQ1 and that CoQ1-dependent PRODH/POX activity required functional Complex III and Complex IV. PRODH/POX supported respiration in living cells during nutrient stress; however, expression of PRODH/POX resulted in an overall decrease in respiratory fitness. Effects on respiratory fitness were inhibited by DHP and NAC, indicating that these effects were mediated by PRODH/POX-dependent reactive oxygen species (ROS) generation. PRODH/POX expression resulted in a dose-dependent down-regulation of Complexes I-IV of the ETC, and this effect was also mitigated by the addition of DHP and NAC. We found that succinate was an uncompetitive inhibitor of PRODH/POX activity, inhibited ROS generation by PRODH/POX, and alleviated PRODH/POX effects on respiratory fitness. The findings demonstrate novel cross-talk between proline and succinate respiration in vivo and provide mechanistic insights into observations from previous animal studies. Our results suggest a potential regulatory loop between PRODH/POX and succinate in regulation of mitochondrial respiration. PMID:26660760

  17. Succinic acid production from acid hydrolysate of corn fiber by Actinobacillus succinogenes.

    PubMed

    Chen, Kequan; Jiang, Min; Wei, Ping; Yao, Jiaming; Wu, Hao

    2010-01-01

    Dilute acid hydrolysate of corn fiber was used as carbon source for the production of succinic acid by Actinobacillus succinogenes NJ113. The optimized hydrolysis conditions were obtained by orthogonal experiments. When corn fiber particles were of 20 mesh in size and treated with 1.0% sulfuric acid at 121 degrees C for 2 h, the total sugar yield could reach 63.3%. It was found that CaCO(3) neutralization combined with activated carbon adsorption was an effective method to remove fermentation inhibitors especially furfural that presented in the acid hydrolysate of corn fiber. Only 5.2% of the total sugar was lost, while 91.9% of furfural was removed. The yield of succinic acid was higher than 72.0% with the detoxified corn fiber hydrolysate as the carbon source in anaerobic bottles or 7.5 L fermentor cultures. It was proved that the corn fiber hydrolysate could be an alternative to glucose for the production of succinic acid by A. succinogenes NJ113. PMID:18830824

  18. Engineering of Corynebacterium glutamicum for growth and succinate production from levoglucosan, a pyrolytic sugar substrate.

    PubMed

    Kim, Eun-Mi; Um, Youngsoon; Bott, Michael; Woo, Han Min

    2015-10-01

    Thermochemical processing provides continuous production of bio-oils from lignocellulosic biomass. Levoglucosan, a pyrolytic sugar substrate C6H10O5 in a bio-oil, has been used for ethanol production using engineered Escherichia coli. Here we provide the first example for succinate production from levoglucosan with Corynebacterium glutamicum, a well-known industrial amino acid producer. Heterologous expression of a gene encoding a sugar kinase from Lipomyces starkeyi, Gibberella zeae or Pseudomonas aeruginosa was employed for levoglucosan conversion in C. glutamicum because the wild type was unable to utilize levoglucosan as sole carbon source. As result, expression of a levoglucosan kinase (LGK) of L. starkeyi only enabled growth with levoglucosan as sole carbon source in CgXII minimal medium by catalyzing conversion of levoglucosan to glucose-6-phosphate. Subsequently, the lgk gene was expressed in an aerobic succinate producer of C. glutamicum, strain BL-1. The recombinant strain showed a higher succinate yield (0.25 g g(-1)) from 2% (w/v) levoglucosan than the reference strain BL-1 from 2% (w/v) glucose (0.19 g g(-1)), confirming that levoglucosan is an attractive carbon substrate for C. glutamicum producer strains. In summary, we demonstrated that a pyrolytic sugar could be a potential carbon source for microbial cell factories. PMID:26363018

  19. The pharmacology of nomegestrol acetate.

    PubMed

    Ruan, Xiangyan; Seeger, Harald; Mueck, Alfred O

    2012-04-01

    Nomegestrol acetate (NOMAC) is a 19-norprogesterone derivative with high biological activity at the progesterone receptor, a weak anti-androgenic effect, but with no binding to estrogen, glucocorticoid or mineralocorticoid receptors. At dosages of 1.5mg/day or more, NOMAC effectively suppresses gonadotropic activity and ovulation in women of reproductive age. Hemostasis, lipids and carbohydrate metabolism remain largely unchanged. In normal and cancerous human breast cells, NOMAC has shown favorable effects on estrogen metabolism. Like natural progesterone (but in contrast to some other synthetic progestogens), it does not appear stimulate the proliferation of cancerous breast cells. While there has been some experience of the use of NOMAC in combination with estrogens as a hormone replacement therapy, most of the data on the compound are reported in the context of its inclusion as a component of a new contraceptive pill comprising 2.5mg NOMAC combined with 1.5mg estradiol. Because of its strong endometrial efficacy, and due to its high antigonadotropic activity and long elimination half-life (about 50h), the contraceptive efficacy of the new pill is maintained even when dosages are missed. Furthermore, for the first time with a monophasic 24/4 regimen containing estradiol, cyclical stability can be achieved comparable with that obtained using pills containing ethinyl estradiol and progestogens like levonorgestrel or drospirenone. The addition of NOMAC to estradiol means that the beneficial effects of estrogen are not lost, which is of especial importance in relation to the cardiovascular system. On the basis both of its pharmacology and of studies performed during the development of the NOMAC/estradiol pill, involving some 4000 women in total, good long-term tolerability can be expected for NOMAC, although its safety profile is still to be fully ascertained, as the clinical endpoint studies are yet to be completed. PMID:22364709

  20. Conversion to eslicarbazepine acetate monotherapy

    PubMed Central

    French, Jacqueline; Jacobson, Mercedes P.; Pazdera, Ladislav; Gough, Mallory; Cheng, Hailong; Grinnell, Todd; Blum, David

    2016-01-01

    Objective: To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy. Methods: This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical control threshold (65.3%). Results: Pooled exit rates were as follows: ESL 1,600 mg = 20.6% (95% confidence interval: 15.6%–26.8%); ESL 1,200 mg = 30.8% (23.0%–40.5%). Use of 2 baseline AEDs or rescue medication, US location, epilepsy duration ≥20 years, and higher maximum baseline seizure frequency were associated with higher exit risks. Median percent reductions in standardized seizure frequency between baseline and the 18-week double-blind period were as follows: ESL 1,600 mg = 43.2%; ESL 1,200 mg = 35.7%; baseline carbamazepine use was associated with smaller reductions. Safety profiles were similar between ESL doses. Conclusions: Exit rates for ESL monotherapy (1,600 mg and 1,200 mg once daily) were lower than the historical control threshold, irrespective of baseline AED use and region, with no additional safety concerns identified. Clinical factors and location clearly influence treatment responses in conversion-to-monotherapy trials. Classification of evidence: This pooled analysis provides Class IV evidence that for adults with medically uncontrolled partial-onset seizures, ESL monotherapy is well tolerated and effective. PMID:26911639

  1. Clostridium thermosaccharolyticum strain deficient in acetate production

    SciTech Connect

    Rothstein, D.M.

    1986-01-01

    A mutant of Clostridium thermosaccharolyticum that is blocked in acetate production was isolated after treatment with nitrosoguanidine and selection for fluoroacetate resistance. The mutant produced more ethanol than the parent strain did.

  2. Acetate Causes Alcohol Hangover Headache in Rats

    PubMed Central

    Maxwell, Christina R.; Spangenberg, Rebecca Jay; Hoek, Jan B.; Silberstein, Stephen D.; Oshinsky, Michael L.

    2010-01-01

    Background The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache. Methods We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats. Results Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate increased nociceptive behaviors suggesting that acetate, not acetaldehyde, accumulation results in hangover-like hypersensitivity in our model. Since adenosine accumulation is a result of acetate formation, we administered an adenosine antagonist that blocked hypersensitivity. Discussion Our study shows that acetate contributes to hangover headache. These findings provide insight into the mechanism of hangover headache and the mechanism of headache induction. PMID:21209842

  3. Mafenide acetate allergy presenting as recurrent chondritis.

    PubMed

    Pickus, Evan J; Lionelli, Gerald T; Charles, E Woodall; Korentager, Richard A

    2002-02-01

    Acute chondritis has a strong predilection for recurrence. Mafenide acetate has been implicated in causing reactions that mimic this condition; however, these hypersensitivity reactions lack fever, fluctuance, and pain. The authors report a case of mafenide acetate allergy presenting as recurrent chondritis in a patient who had previously been treated successfully for this condition. In this patient, the allergic response resolved within 3 days after cessation of mafenide acetate. If unappreciated, it may have led to unnecessary operative intervention. Therefore, auricular edema and erythema, without fever, fluctuance, and pain, must be recognized by surgeons as a possible mafenide acetate allergy and must be considered in the differential diagnosis for patients who present with recurrent acute suppurative chondritis. PMID:11910229

  4. A genomic perspective on the potential of Actinobacillus succinogenes for industrial succinate production

    PubMed Central

    2010-01-01

    Background Succinate is produced petrochemically from maleic anhydride to satisfy a small specialty chemical market. If succinate could be produced fermentatively at a price competitive with that of maleic anhydride, though, it could replace maleic anhydride as the precursor of many bulk chemicals, transforming a multi-billion dollar petrochemical market into one based on renewable resources. Actinobacillus succinogenes naturally converts sugars and CO2 into high concentrations of succinic acid as part of a mixed-acid fermentation. Efforts are ongoing to maximize carbon flux to succinate to achieve an industrial process. Results Described here is the 2.3 Mb A. succinogenes genome sequence with emphasis on A. succinogenes's potential for genetic engineering, its metabolic attributes and capabilities, and its lack of pathogenicity. The genome sequence contains 1,690 DNA uptake signal sequence repeats and a nearly complete set of natural competence proteins, suggesting that A. succinogenes is capable of natural transformation. A. succinogenes lacks a complete tricarboxylic acid cycle as well as a glyoxylate pathway, and it appears to be able to transport and degrade about twenty different carbohydrates. The genomes of A. succinogenes and its closest known relative, Mannheimia succiniciproducens, were compared for the presence of known Pasteurellaceae virulence factors. Both species appear to lack the virulence traits of toxin production, sialic acid and choline incorporation into lipopolysaccharide, and utilization of hemoglobin and transferrin as iron sources. Perspectives are also given on the conservation of A. succinogenes genomic features in other sequenced Pasteurellaceae. Conclusions Both A. succinogenes and M. succiniciproducens genome sequences lack many of the virulence genes used by their pathogenic Pasteurellaceae relatives. The lack of pathogenicity of these two succinogens is an exciting prospect, because comparisons with pathogenic Pasteurellaceae could

  5. Nomegestrol acetate/estradiol: in oral contraception.

    PubMed

    Yang, Lily P H; Plosker, Greg L

    2012-10-01

    Nomegestrol acetate/estradiol is a combined oral contraceptive with approval in many countries. This fixed-dose combination tablet contains nomegestrol acetate, a highly selective progestogen, and estradiol, a natural estrogen. It is the first monophasic combined oral contraceptive to contain estradiol, and is taken in 28-day cycles, consisting of 24 active therapy days with 4 placebo days (i.e. 24/4-day cycles). In two large, 1-year, randomized, open-label, multicentre, phase III trials in healthy adult women (aged 18-50 years), nomegestrol acetate/estradiol was at least as effective as drospirenone/ethinylestradiol as contraceptive therapy, as the pregnancy rates in women aged 18-35 years (primary efficacy population) in terms of the Pearl Index (primary endpoint) were numerically lower with nomegestrol acetate/estradiol, although the between-group difference was not statistically significant. In both trials, nomegestrol acetate/estradiol was given in a 24/4-day cycle, and drospirenone/ethinylestradiol was given in a 21/7-day cycle. The criteria for using condoms in case of forgotten doses were less stringent in the nomegestrol acetate/estradiol group than in the drospirenone/ethinylestradiol group. Nomegestrol acetate/estradiol therapy for up to 1 year was generally well tolerated in healthy adult women, with an acceptable tolerability profile in line with that expected for a combined oral contraceptive. The most commonly reported adverse events were acne and abnormal withdrawal bleeding (most often shorter, lighter or absent periods). Overall, compared with drospirenone/ethinylestradiol, nomegestrol acetate/estradiol appeared to be associated with less favourable acne-related outcomes, and shorter, lighter or absent periods. PMID:22950535

  6. Methanogenesis from acetate: a nonmethanogenic bacterium from an anaerobic acetate enrichment.

    PubMed

    Ward, D M; Mah, R A; Kaplan, I R

    1978-06-01

    A methanogenic acetate enrichment was initiated by inoculation of an acetate-mineral salts medium with domestic anaerobic digestor sludge and maintained by weekly transfer for 2 years. The enrichment culture contained a Methanosarcina and several obligately anaerobic nonmethanogenic bacteria. These latter organisms formed varying degrees of association with the Methanosarcina, ranging from the nutritionally fastidious gram-negative rod called the satellite bacterium to the nutritionally nonfastidious Eubacterium limosum. The satellite bacterium had growth requirements for amino acids, a peptide, a purine base, vitamin B12, and other B vitamins. Glucose, mannitol, starch, pyruvate, cysteine, lysine, leucine, isoleucine, arginine, and asparagine stimulated growth and hydrogen production. Acetate was neither incorporated nor metabolized by the satellite organism. Since acetate was the sole organic carbon source in the enrichment culture, organism(s) which metabolize acetate (such as the Methanosarcina) must produce substrates and growth factors for associated organisms which do not metabolize acetate. PMID:677881

  7. Molecular mobility in glassy dispersions.

    PubMed

    Mehta, Mehak; McKenna, Gregory B; Suryanarayanan, Raj

    2016-05-28

    Dielectric spectroscopy was used to characterize the structural relaxation in pharmaceutical dispersions containing nifedipine (NIF) and either poly(vinyl) pyrrolidone (PVP) or hydroxypropyl methylcellulose acetate succinate (HPMCAS). The shape of the dielectric response (permittivity versus log time) curve was observed to be independent of temperature. Thus, for the pure NIF as well as the dispersions, the validity of the time-temperature superposition principle was established. Furthermore, though the shape of the full dielectric response varied with polymer concentration, the regime related to the α- or structural relaxation was found to superimpose for the dispersions, though not with the response of the NIF itself. Hence, there is a limited time-temperature-concentration superposition for these systems as well. Therefore, in this polymer concentration range, calculation of long relaxation times in these glass-forming systems becomes possible. We found that strong drug-polymer hydrogen bonding interactions improved the physical stability (i.e., delayed crystallization) by reducing the molecular mobility. The strength of hydrogen bonding, structural relaxation time, and crystallization followed the order: NIF-PV P>NIF-HPMCAS>NIF. With an increase in polymer concentration, the relaxation times were longer indicating a decrease in molecular mobility. The temperature dependence of relaxation time, in other words fragility, was independent of polymer concentration. This is the first application of the superposition principle to characterize structural relaxation in glassy pharmaceutical dispersions. PMID:27250315

  8. Molecular mobility in glassy dispersions

    NASA Astrophysics Data System (ADS)

    Mehta, Mehak; McKenna, Gregory B.; Suryanarayanan, Raj

    2016-05-01

    Dielectric spectroscopy was used to characterize the structural relaxation in pharmaceutical dispersions containing nifedipine (NIF) and either poly(vinyl) pyrrolidone (PVP) or hydroxypropyl methylcellulose acetate succinate (HPMCAS). The shape of the dielectric response (permittivity versus log time) curve was observed to be independent of temperature. Thus, for the pure NIF as well as the dispersions, the validity of the time-temperature superposition principle was established. Furthermore, though the shape of the full dielectric response varied with polymer concentration, the regime related to the α- or structural relaxation was found to superimpose for the dispersions, though not with the response of the NIF itself. Hence, there is a limited time-temperature-concentration superposition for these systems as well. Therefore, in this polymer concentration range, calculation of long relaxation times in these glass-forming systems becomes possible. We found that strong drug-polymer hydrogen bonding interactions improved the physical stability (i.e., delayed crystallization) by reducing the molecular mobility. The strength of hydrogen bonding, structural relaxation time, and crystallization followed the order: NIF-PV P>NIF-HPMCAS>NIF. With an increase in polymer concentration, the relaxation times were longer indicating a decrease in molecular mobility. The temperature dependence of relaxation time, in other words fragility, was independent of polymer concentration. This is the first application of the superposition principle to characterize structural relaxation in glassy pharmaceutical dispersions.

  9. Stability of dry coated solid dosage forms.

    PubMed

    Kablitz, Caroline Désirée; Urbanetz, Nora Anne

    2009-01-01

    The dry coating process was evaluated in terms of storage stability investigating drug release and agglomeration tendency of the different coated oral dosage forms; hydroxypropyl methylcellulose acetate succinate (HPMCAS) was used with triethylcitrate (TEC) as plasticizer and acetylated monoglyceride (Myvacet) as wetting agent. Talc or colloidal silicon dioxide (Aerosil) was used as anti-tacking agents. In contrast to coating formulations consisting of HPMCAS and Myvacet all formulations containing TEC showed enteric resistance and no agglomeration tendency after preparation. After storage at 10% RH +/- 5% enteric resistance is increased slightly. This increase is more pronounced at 60% RH +/- 5%. The formulations without anti-tacking agents showed higher drug releases after 12 and 24 months due to the damage of the film's integrity during sample preparation caused by the high tackiness of the film. Tackiness is not affected by storing if samples are stored at low relative humidity. At high relative humidity tackiness increases upon storage especially for formulations without anti-tacking agents. The sieving results of the agglomeration measurements after storage can be confirmed by ring shear measurements performed immediately after preparation and approved to be a tool, which is able to predict the agglomeration during storage. PMID:19883250

  10. Acetohydroxy acid synthase I, a required enzyme for isoleucine and valine biosynthesis in Escherichia coli K-12 during growth on acetate as the sole carbon source.

    PubMed Central

    Dailey, F E; Cronan, J E

    1986-01-01

    Escherichia coli K-12 has two acetohydroxy acid synthase (AHAS) isozymes (AHAS I and AHAS III). Both of these isozymes catalyze the synthesis of alpha-aceto-alpha-hydroxybutyrate and alpha-acetolactate, which are key intermediates of the isoleucine-valine biosynthetic pathway. Strains lacking either isozyme but not both activities have been previously shown to grow well in minimal media in the absence of isoleucine and valine on any of several commonly used carbon sources (e.g., glucose or succinate). We report the characterization of mutants that were unable to grow on either acetate or oleate as a sole carbon source due to a defect in isoleucine-valine biosynthesis. The defect in isoleucine-valine biosynthesis was expressed only on these carbon sources and was due to the loss of AHAS I activity, resulting from lesions in the ilvBN operon. Previously identified ilvBN mutant strains also failed to grow on acetate or oleate minimal media. Our results indicated that AHAS I is an essential enzyme for isoleucine and valine biosynthesis when E. coli K-12 is grown on acetate or oleate as the sole carbon source. AHAS III was expressed during growth on acetate or oleate but was somehow unable to produce sufficient amounts of alpha-aceto-alpha-hydroxybutyrate and alpha-acetolactate to allow growth. PMID:3511034

  11. Performance of biodegradable microcapsules of poly(butylene succinate), poly(butylene succinate-co-adipate) and poly(butylene terephthalate-co-adipate) as drug encapsulation systems.

    PubMed

    Brunner, Cornelia Theresa; Baran, Erkan Türker; Pinho, Elisabete Duarte; Reis, Rui Luís; Neves, Nuno Meleiro

    2011-06-01

    Poly(butylene succinate) (PBSu), poly(butylene succinate-co-adipate) (PBSA) and poly(butylene terephthalate-co-adipate) (PBTA) microcapsules were prepared by the double emulsion/solvent evaporation method. The effect of polymer and poly(vinyl alcohol) (PVA) concentration on the microcapsule morphologies, drug encapsulation efficiency (EE) and drug loading (DL) of bovine serum albumin (BSA) and all-trans retinoic acid (atRA) were all investigated. As a result, the sizes of PBSu, PBSA and PBTA microcapsules were increased significantly by varying polymer concentrations from 6 to 9%. atRA was encapsulated into the microcapsules with an high level of approximately 95% EE. The highest EE and DL of BSA were observed at 1% polymer concentration in values of 60 and 37%, respectively. 4% PVA was found as the optimum concentration and resulted in 75% EE and 14% DL of BSA. The BSA release from the capsules of PBSA was the longest, with 10% release in the first day and a steady release of 17% until the end of day 28. The release of atRA from PBSu microcapsules showed a zero-order profile for 2 weeks, keeping a steady release rate during 4 weeks with a 9% cumulative release. Similarly, the PBSA microcapsules showed a prolonged and a steady release of atRA during 6 weeks with 12% release. In the case of PBTA microcapsules, after a burst release of 10% in the first day, showed a parabolic release profile of atRA during 42 days, releasing 36% of atRA. PMID:21376545

  12. Adrenocortical suppression in cats given megestrol acetate.

    PubMed

    Chastain, C B; Graham, C L; Nichols, C E

    1981-12-01

    Megestrol acetate was given orally to 8 cats at a dose of 2.5 mg every other day for 2 weeks and to 8 cats at a dose of 5.0 mg every day for 2 weeks. Four cats were designated nontreated controls. Pre-ACTH-stimulated plasma concentrations of cortisol (hydrocortisone) and ACTH-stimulated cortisol and tolerance to large-dose glucose infusion (IV) were determined on each of the 20 cats given megestrol acetate. Cats were restrained with acepromazine maleate and ketamine hydrochloride during blood sample collection and large-dose glucose infusion. Adrenocortical function and tolerance to large-dose glucose infusion were reevaluated for 4 weeks--after 1st and 2nd weeks of megestrol acetate treatment of the treated groups, and after 1st and 2nd weeks when treatment was stopped (ie, experiment weeks 3 and 4). Each week a cat from the control group and 2 cats from the 2 treated groups were selected to determine the changes occurring during the experiment for that week; after collection of plasma samples, each week's 5 selected cats were euthanatized and necropsied. Significant impairment of adrenocortical function and alteration of adrenocortical morphology occurred with both treated groups. The most severe adrenocortical alterations occurred in the cats 1 week after megestrol acetate was no longer given (ie, experiment week 3). Megestrol acetate-induced adrenocortical suppression contributed to the death of 1 cat. It was concluded that if stress occurs to cats on treatment or soon after treatment with megestrol acetate, glucocorticoids should be supplemented. The effects of megestrol acetate on glucose tolerance were overshadowed by the unforeseen intolerance caused by chemical restraint with acepromazine maleate and ketamine hydrochloride. PMID:6280517

  13. Acetate Transport and Utilization in the Rat Brain

    PubMed Central

    Deelchand, Dinesh K.; Shestov, Alexander A.; Koski, Dee M.; Uğurbil, Kâmil; Henry, Pierre-Gilles

    2009-01-01

    Acetate, a glial-specific substrate, is an attractive alternative to glucose for the study of neuronal-glial interactions. The present study investigates the kinetics of acetate uptake and utilization in the rat brain in vivo during infusion of [2-13C]acetate using NMR spectroscopy. When plasma acetate concentration was increased, the rate of brain acetate utilization (CMRace) increased progressively and reached close to saturation for plasma acetate concentration > 2-3 mM, whereas brain acetate concentration continued to increase. The Michaelis-Menten constant for brain acetate utilization ( KMutil=0.01±0.14mM) was much smaller than for acetate transport through the blood-brain barrier ( KMt=4.18±0.83mM). The maximum transport capacity of acetate through the blood-brain barrier ( Vmaxt=0.96±0.18μmol/g/min) was nearly two-fold higher than the maximum rate of brain acetate utilization ( Vmaxutil=0.50±0.08μmol/g/min). We conclude that, under our experimental conditions, brain acetate utilization is saturated when plasma acetate concentrations increase above 2-3 mM. At such high plasma acetate concentration, the rate-limiting step for glial acetate metabolism is not the blood-brain barrier, but occurs after entry of acetate into the brain. PMID:19393008

  14. Redox State of Flavin Adenine Dinucleotide Drives Substrate Binding and Product Release in Escherichia coli Succinate Dehydrogenase

    PubMed Central

    Cheng, Victor W.T.; Piragasam, Ramanaguru Siva; Rothery, Richard A.; Maklashina, Elena; Cecchini, Gary; Weiner, Joel H.

    2016-01-01

    The Complex II family of enzymes, comprising the respiratory succinate dehydrogenases and fumarate reductases, catalyze reversible interconversion of succinate and fumarate. In contrast to the covalent flavin adenine dinucleotide (FAD) cofactor assembled in these enzymes, the soluble fumarate reductases (e.g. that from Shewanella frigidimarina) that assemble a noncovalent FAD cannot catalyze succinate oxidation but retain the ability to reduce fumarate. In this study, an SdhA-H45A variant that eliminates the site of the 8α-N3-histidyl covalent linkage between the protein and the FAD was examined. The variants SdhA-R286A/K/Y and -H242A/Y, that target residues thought to be important for substrate binding and catalysis were also studied. The variants SdhA-H45A and -R286A/K/Y resulted in assembly of a noncovalent FAD cofactor, which led to a significant decrease (−87 mV or more) in its reduction potential. The variant enzymes were studied by electron paramagnetic resonance spectroscopy following stand-alone reduction and potentiometric titrations. The “free” and “occupied” states of the active site were linked to the reduced and oxidized states of the FAD, respectively. Our data allows for a proposed model of succinate oxidation that is consistent with tunnel diode effects observed in the succinate dehydrogenase enzyme and a preference for fumarate reduction catalysis in fumarate reductase homologues that assemble a noncovalent FAD. PMID:25569225

  15. Succinate Accumulation and Ischemia-Reperfusion Injury: Of Mice but Not Men, a Study in Renal Ischemia-Reperfusion.

    PubMed

    Wijermars, L G M; Schaapherder, A F; Kostidis, S; Wüst, R C I; Lindeman, J H

    2016-09-01

    A recent seminal paper implicated ischemia-related succinate accumulation followed by succinate-driven reactive oxygen species formation as a key driver of ischemia-reperfusion injury. Although the data show that the mechanism is universal for all organs tested (kidney, liver, heart, and brain), a remaining question is to what extent these observations in mice translate to humans. We showed in this study that succinate accumulation is not a universal event during ischemia and does not occur during renal graft procurement; in fact, tissue succinate content progressively decreased with increasing graft ischemia time (p < 0.007). Contrasting responses were also found with respect to mitochondrial susceptibility toward ischemia and reperfusion, with rodent mitochondria robustly resistant toward warm ischemia but human and pig mitochondria highly susceptible to warm ischemia (p < 0.05). These observations suggest that succinate-driven reactive oxygen formation does not occur in the context of kidney transplantation. Moreover, absent allantoin release from the reperfused grafts suggests minimal oxidative stress during clinical reperfusion. PMID:26999803

  16. Modulation of drug release rate of diltiazem-HCl from hydrogel matrices of succinic acid-treated ispaghula husk.

    PubMed

    Gohel, M C; Amin, A F; Chhabaria, M T; Panchal, M K; Lalwani, A N

    2000-01-01

    The feasibility of using succinic acid-treated ispaghula husk in matrix-based tablets of diltiazem-HCl was investigated. The sample prepared using 4:1 weight ratio of ispaghula husk to succinic acid showed improved swelling and gelling. A 3(2) factorial design was employed to investigate the effect of amount of succinic acid-treated ispaghula husk and dicalcium phosphate (DCP) on the percentage of the drug dissolved in 60, 300, and 480 min from the compressed tablets. The results of multiple linear regression analysis revealed that the significance of the amount of succinic acid-treated ispaghula husk was greater in magnitude than that of the amount of DCP in controlling the drug release. Acceptable batches were identified from a contour plot with constraints on the percentage drug released at the three sampling times. A mathematical model was also evolved to describe the entire dissolution profile. The results of F-test revealed that the Higuchi model fits well to the in vitro dissolution data. The tablets showed considerable radial and axial swelling in distilled water. Succinic acid-treated ispaghula husk can be used as an economical hydrophilic matrixing agent. PMID:10934737

  17. Decreased succinate dehydrogenase activity of gamma and alpha motoneurons in mouse spinal cords following 13 weeks of exposure to microgravity.

    PubMed

    Ishihara, Akihiko; Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Ohira, Yoshinobu

    2013-10-01

    Cell body size and succinate dehydrogenase activity of motoneurons in the dorsolateral region of the ventral horn in the lumbar and cervical segments of the mouse spinal cord were assessed after long-term exposure to microgravity and compared with those of ground-based controls. Mice were housed in a mouse drawer system on the International Space Station for 13 weeks. The mice were transported to the International Space Station by the Space Shuttle Discovery and returned to Earth by the Space Shuttle Atlantis. No changes in the cell body size of motoneurons were observed in either segment after exposure to microgravity, but succinate dehydrogenase activity of small-sized (<300 μm(2)) gamma and medium-sized (300-700 μm(2)) alpha motoneurons, which have higher succinate dehydrogenase activity than large-sized (>700 μm(2)) alpha motoneurons, in both segments was lower than that of ground-based controls. We concluded that exposure to microgravity for longer than 3 months induced decreased succinate dehydrogenase activity of both gamma and slow-type alpha motoneurons. In particular, the decreased succinate dehydrogenase activity of gamma motoneurons was observed only after long-term exposure to microgravity. PMID:23943522

  18. Cytoplasm-to-myonucleus ratios and succinate dehydrogenase activities in adult rat slow and fast muscle fibers

    NASA Technical Reports Server (NTRS)

    Tseng, B. S.; Kasper, C. E.; Edgerton, V. R.

    1994-01-01

    The relationship between myonuclear number, cellular size, succinate dehydrogenase activity, and myosin type was examined in single fiber segments (n = 54; 9 +/- 3 mm long) mechanically dissected from soleus and plantaris muscles of adult rats. One end of each fiber segment was stained for DNA before quantitative photometric analysis of succinate dehydrogenase activity; the other end was double immunolabeled with fast and slow myosin heavy chain monoclonal antibodies. Mean +/- S.D. cytoplasmic volume/myonucleus ratio was higher in fast and slow plantaris fibers (112 +/- 69 vs. 34 +/- 21 x 10(3) microns3) than fast and slow soleus fibers (40 +/- 20 vs. 30 +/- 14 x 10(3) microns3), respectively. Slow fibers always had small volumes/myonucleus, regardless of fiber diameter, succinate dehydrogenase activity, or muscle of origin. In contrast, smaller diameter (< 70 microns) fast soleus and plantaris fibers with high succinate dehydrogenase activity appeared to have low volumes/myonucleus while larger diameter (> 70 microns) fast fibers with low succinate dehydrogenase activity always had large volume/myonucleus. Slow soleus fibers had significantly greater numbers of myonuclei/mm than did either fast soleus or fast plantaris fibers (116 +/- 51 vs. 55 +/- 22 and 44 +/- 23), respectively. These data suggest that the myonuclear domain is more limited in slow than fast fibers and in the fibers with a high, compared to a low, oxidative metabolic capability.

  19. Redox state of flavin adenine dinucleotide drives substrate binding and product release in Escherichia coli succinate dehydrogenase.

    PubMed

    Cheng, Victor W T; Piragasam, Ramanaguru Siva; Rothery, Richard A; Maklashina, Elena; Cecchini, Gary; Weiner, Joel H

    2015-02-01

    The Complex II family of enzymes, comprising respiratory succinate dehydrogenases and fumarate reductases, catalyzes reversible interconversion of succinate and fumarate. In contrast to the covalent flavin adenine dinucleotide (FAD) cofactor assembled in these enzymes, soluble fumarate reductases (e.g., those from Shewanella frigidimarina) that assemble a noncovalent FAD cannot catalyze succinate oxidation but retain the ability to reduce fumarate. In this study, an SdhA-H45A variant that eliminates the site of the 8α-N3-histidyl covalent linkage between the protein and FAD was examined. Variants SdhA-R286A/K/Y and -H242A/Y that target residues thought to be important for substrate binding and catalysis were also studied. The variants SdhA-H45A and -R286A/K/Y resulted in the assembly of a noncovalent FAD cofactor, which led to a significant decrease (-87 mV or more) in its reduction potential. The variant enzymes were studied by electron paramagnetic resonance spectroscopy following stand-alone reduction and potentiometric titrations. The "free" and "occupied" states of the active site were linked to the reduced and oxidized states of FAD, respectively. Our data allow for a proposed model of succinate oxidation that is consistent with tunnel diode effects observed in the succinate dehydrogenase enzyme and a preference for fumarate reduction catalysis in fumarate reductase homologues that assemble a noncovalent FAD. PMID:25569225

  20. Performance analyses of a neutralizing agent combination strategy for the production of succinic acid by Actinobacillus succinogenes ATCC 55618.

    PubMed

    Wang, Cheng-Cheng; Zhu, Li-Wen; Li, Hong-Mei; Tang, Ya-Jie

    2012-05-01

    A neutralizing agent combination strategy was developed to enhance the succinic acid production by Actinobacillus succinogenes ATCC 55618. First, a maximal succinic acid production of 48.2 g/L was obtained at a culture pH of 7.5. Second, NaOH and KOH were screened to identify the optimal neutralizing agent for pH control. However, the production of succinic acid did not increase, and severe cell flocculation was observed due to a high concentration of metal ions when only one neutralizing agent was used to control pH. Finally, a neutralizing agent combination strategy was developed with a supply of neutralizing agents with OH(-) and carbonate. The cell flocculation was eliminated, and a maximum succinic acid production of 59.2 g/L was obtained with 5 M NaOH and 40 g/L of MgCO(3); this production was 27.9% higher than that obtained with NaOH alone. The results obtained in this study may be useful for the large-scale industrial production of succinic acid. PMID:22002101

  1. Tested Demonstrations: Buffer Capacity of Various Acetic Acid-Sodium Acetate Systems: A Lecture Experiment.

    ERIC Educational Resources Information Center

    Donahue, Craig J.; Panek, Mary G.

    1985-01-01

    Background information and procedures are provided for a lecture experiment which uses indicators to illustrate the concept of differing buffer capacities by titrating acetic acid/sodium acetate buffers with 1.0 molar hydrochloric acid and 1.0 molar sodium hydroxide. A table with data used to plot the titration curve is included. (JN)

  2. Acetylation of Starch with Vinyl Acetate in Imidazolium Ionic Liquids and Characterization of Acetate Distribution

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Starch was acetylated with vinyl acetate in different 1-butyl-3-methylimidazolium (BMIM) salts as solvent in effort to produce starches with different acetylation patterns. Overall degree of substitution was much higher for basic anions such as acetate and dicyanimide (dca) than for neutral anions ...

  3. 40 CFR 721.10001 - 2-Ethoxyethanol, 2-ethoxyethanol acetate, 2-methoxyethanol, and 2-methoxyethanol acetate.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... new uses subject to reporting. (1) The chemical substances identified as 2-ethoxyethanol (CAS No. 110-80-5), 2-ethoxyethanol acetate (CAS No. 111-15-9), 2-methoxyethanol (CAS No. 109-86-4), and 2-methoxyethanol acetate (CAS No. 110-49-6) are subject to reporting under this section for the significant new...

  4. 40 CFR 721.10001 - 2-Ethoxyethanol, 2-ethoxyethanol acetate, 2-methoxyethanol, and 2-methoxyethanol acetate.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... new uses subject to reporting. (1) The chemical substances identified as 2-ethoxyethanol (CAS No. 110-80-5), 2-ethoxyethanol acetate (CAS No. 111-15-9), 2-methoxyethanol (CAS No. 109-86-4), and 2-methoxyethanol acetate (CAS No. 110-49-6) are subject to reporting under this section for the significant new...

  5. [Degradation of thiometon in ethyl acetate].

    PubMed

    Satoh, M; Shimokawa, S; Kobata, M; Tanaka, T; Nakanishi, Y

    2001-04-01

    When performing multiresidue analysis of pesticides, the recovery of thiometon was less than 20% from carrots and eggplants, but about 100% from garlic chives and welsh onions. The recovery of thiometon was found to depend on the lot of ethyl acetate. A 2-year-old lot of ethyl acetate caused degradation of thiometon, but a fresh lot of ethyl acetate did not. Analysis showed that ethyl acetate stored for 2 years contained about 5 microL/mL of acetaldehyde. Thiometon was also degraded by acetone or acetonitrile, when acetaldehyde was added to them, in the same manner as by aged ethyl acetate. The fact that the recovery of thiometon from welsh onions was about 100% indicated that some of the mercaptans in allium vegetables may prevent thiometon degradation. Mercaptans such as L-cysteine and 3-mercaptoproionic acid were confirmed to prevent the degradation of thiometon and disulfoton. These findings show that mercaptans may be useful additives for analyzing thiometon and disulfoton. PMID:11486375

  6. A New Specific Succinate-Glutamate Metabolomic Hallmark in Sdhx-Related Paragangliomas

    PubMed Central

    Imperiale, Alessio; Moussallieh, François-Marie; Sebag, Frédéric; Brunaud, Laurent; Barlier, Anne; Elbayed, Karim; Bachellier, Philippe; Goichot, Bernard; Pacak, Karel; Namer, Izzie-Jacques; Taïeb, David

    2013-01-01

    Paragangliomas (PGLs) are frequently associated with germline mutations in genes involved in energy metabolism. The purpose of the present study was to assess whether the tumor metabolomic profile of patients with hereditary and apparently sporadic PGLs enables the distinction of different subtypes of tumors. Twenty-eight unrelated patients with a histological diagnosis of PGLs were included in the present study. Twelve had germline mutations in SDHx genes (5 SDHB, 7 SDHD), 6 VHL, and 10 were apparently sporadic. Intact tumor samples from these patients (one per patient) were evaluated with 1H high-resolution magic angle spinning (HRMAS) NMR spectroscopy. SDHx-related tumors were characterized by an increase in succinate levels in comparison to other tumor subtypes (p = 0.0001 vs VHL and p = 0.000003 vs apparently sporadic). Furthermore, we found significantly lower values of glutamate in SDHx-related tumors compared to other subtypes (p = 0.0007 vs VHL and p = 0.003 vs apparently sporadic). Moreover, SDHx-tumors also exhibited lower values of ATP/ADP/AMP (p = 0.01) compared to VHL. VHL tumors were found to have the highest values of glutathione (GSH) compared to other tumors. Based on 4 metabolites (succinate, glutamate, GSH, and ATP/ADP/AMP), tumors were accurately distinguished from the other ones on both 3- and 2-class PLS-DA models. The present study shows that HRMAS NMR spectroscopy is a very promising method for investigating the metabolomic profile of various PGLs. The present data suggest the existence of a specific succinate-glutamate hallmark of SDHx PGLs. The relevance of such a metabolomic hallmark is expected to be very useful in designing novel treatment options as well as improving the diagnosis and follow-up of these tumors, including metastatic ones. PMID:24312232

  7. Enhanced succinic acid production in Aspergillus saccharolyticus by heterologous expression of fumarate reductase from Trypanosoma brucei.

    PubMed

    Yang, Lei; Lübeck, Mette; Ahring, Birgitte K; Lübeck, Peter S

    2016-02-01

    Aspergillus saccharolyticus exhibits great potential as a cell factory for industrial production of dicarboxylic acids. In the analysis of the organic acid profile, A. saccharolyticus was cultivated in an acid production medium using two different pH conditions. The specific activities of the enzymes, pyruvate carboxylase (PYC), malate dehydrogenase (MDH), and fumarase (FUM), involved in the reductive tricarboxylic acid (rTCA) branch, were examined and compared in cells harvested from the acid production medium and a complete medium. The results showed that ambient pH had a significant impact on the pattern and the amount of organic acids produced by A. saccharolyticus. The wild-type strain produced higher amount of malic acid and succinic acid in the pH buffered condition (pH 6.5) compared with the pH non-buffered condition. The enzyme assays showed that the rTCA branch was active in the acid production medium as well as the complete medium, but the measured enzyme activities were different depending on the media. Furthermore, a soluble NADH-dependent fumarate reductase gene (frd) from Trypanosoma brucei was inserted and expressed in A. saccharolyticus. The expression of the frd gene led to an enhanced production of succinic acid in frd transformants compared with the wild-type in both pH buffered and pH non-buffered conditions with highest amount produced in the pH buffered condition (16.2 ± 0.5 g/L). This study demonstrates the feasibility of increasing succinic acid production through the cytosolic reductive pathway by genetic engineering in A. saccharolyticus. PMID:26521243

  8. Towards Real-time Metabolic Profiling of Cancer with Hyperpolarized Succinate

    PubMed Central

    Zacharias, Niki M.; McCullough, Christopher R.; Wagner, Shawn; Sailasuta, Napapon; Chan, Henry R.; Lee, Youngbok; Hu, Jingzhe; Perman, William H.; Henneberg, Cameron; Ross, Brian D.; Bhattacharya, Pratip

    2016-01-01

    Purpose The energy-yielding mitochondrial Krebs cycle has been shown in many cancers and other diseases to be inhibited or mutated. In most cells, the Krebs cycle with oxidative phosphorylation generates approximately 90% of the adenosine triphosphate in the cell. We designed and hyperpolarized carbon-13 labeled succinate (SUC) and its derivative diethyl succinate (DES) to interrogate the Krebs cycle in real-time in cancer animal models. Procedures Using Parahydrogen Induced Polarization (PHIP), we generated hyperpolarized SUC and DES by hydrogenating their respective fumarate precursors. DES and SUC metabolism was studied in five cancer allograft animal models: breast (4T1), Renal Cell Carcinoma (RENCA), colon (CT26), lymphoma NSO, and lymphoma A20. Results The extent of hyperpolarization was 8 ± 2% for SUC and 2.1 ± 0.6% for DES. The metabolism of DES and SUC in the Krebs cycle could be followed in animals 5 s after tail vein injection. The biodistribution of the compounds was observed using 13C FISP imaging. We observed significant differences in uptake and conversion of both compounds in different cell types both in vivo and in vitro. Conclusion With hyperpolarized DES and SUC, we are able to meet many of the requirements for a useable in vivo metabolic imaging compound – high polarization, relatively long T1 values, low toxicity and high water solubility. However, succinate and its derivative DES are metabolized robustly by RENCA but not by the other cancer models. Our results underscore the heterogeneity of cancer cells and the role cellular uptake plays in hyperpolarized metabolic spectroscopy.

  9. Adsorption of alkenyl succinic anhydride from solutions in carbon tetrachloride on a fine magnetite surface

    NASA Astrophysics Data System (ADS)

    Balmasova, O. V.; Ramazanova, A. G.; Korolev, V. V.

    2016-06-01

    The adsorption of alkenyl succinic anhydride from a solution in carbon tetrachloride on a fine magnetite surface at a temperature of 298.15 K is studied using fine magnetite, which forms the basis of magnetic fluids, as the adsorbent. An adsorption isotherm is recorded and interpreted in terms of the theory of the volume filling of micropores (TVFM). Adsorption process parameters are calculated on the basis of the isotherm. It is shown that at low equilibrium concentrations, the experimental adsorption isotherm is linear in the TVFM equation coordinates.

  10. Studies on synthesis, growth, structural, optical properties of organic 8-hydroxyquinolinium succinate single crystals

    NASA Astrophysics Data System (ADS)

    Thirumurugan, R.; Anitha, K.

    2014-04-01

    8-hydroxyquinolinium succinate (8HQSU), an organic material has been synthesized and single crystals were grown by employing the technique of slow evaporation. The structure of the grown crystal was elucidated by using single crystal X-ray diffraction analysis. 8HQSU crystal belongs to the monoclinic crystallographic system with non-centro symmetric space group of P21. FT-IR spectral investigation has been carried out to identify the various functional groups present in the grown crystal. UV-vis spectral studies reveal that 8HQSU crystals are transparent in the entire visible region and the cut-off wavelength has been found to be 220nm.

  11. Studies on synthesis, growth, structural, optical properties of organic 8-hydroxyquinolinium succinate single crystals

    SciTech Connect

    Thirumurugan, R. Anitha, K.

    2014-04-24

    8-hydroxyquinolinium succinate (8HQSU), an organic material has been synthesized and single crystals were grown by employing the technique of slow evaporation. The structure of the grown crystal was elucidated by using single crystal X-ray diffraction analysis. 8HQSU crystal belongs to the monoclinic crystallographic system with non-centro symmetric space group of P2{sub 1}. FT-IR spectral investigation has been carried out to identify the various functional groups present in the grown crystal. UV–vis spectral studies reveal that 8HQSU crystals are transparent in the entire visible region and the cut-off wavelength has been found to be 220nm.

  12. [Age-related Peculiarities of Succinate Effect on Induced Lipid Peroxidation in Rat Liver Mitochondria].

    PubMed

    Grishina, E V; Khaustova, Ya V; Vasilieva, A A; Mayevsky, E I

    2015-01-01

    The antioxidant effect of succinate and 3-hydroxybutyrate oxidation on the kinetics of lipid peroxidation induced by ATP-Fe2+ complex in isolated rat liver mitochondria of old (1.0-1.5 years) and young (3 months) male rats was investigated. The rate of induced lipid peroxidation V(LPO) in rat liver mitochondria and the half-time of oxygen consumption Δt50, which included the lag period and the initiation. phase, was recorded polarographically. Without exogenous oxidative-substrates V(LPO) was slightly higher in mitochondria of old animals, but the onset of lipid peroxidation cascade was significantly earlier than in young animals. Incubation of mitochondria with 5mM succinate for 1 min inhibited V(LPO) by 15% in young animals and by 35% in old animals. However, only in mitochondria of old animals Δt50 increased by 19% as compared to lipid peroxidation without substrates. V(LPO) in mitochondria of young animals did not significantly change during 3-hydroxybutyrate oxidation, while in mitochondria of old animals it was reduced by 19% with a slight increase in Δt50. To simulate age-dependent dysfunction we damaged isolated mitochondria by a series of freeze-thaw cycles, which caused a significant increase of V(LPO) of.both age groups. Succinate oxidation inhibited V(LPO) in damaged mitochondria in all cases by 56%, as compared to V(LPO) without oxidative substrates and extended At50 twofold in mitochondria of young animals. Oxidation of 3-hydroxybutyrate had no effect on V(LPO) in damaged mitochondria regardless of animal, age and extended Δt50 by 48% in mitochondria of young animals. Thus, the antioxidant effect of succinate oxidation can prevent lipid peroxidation damage and may exhibit geroprotective action at the level of aging mitochondria. Therefore, the antioxidant effect is due to the process of substrate oxidation in the respiratory chain but not because of an interaction of their structures with membrane lipids per se. PMID:26394470

  13. Multifunctional Nanobiocomposite of Poly[(butylene succinate)-co-adipate] and Clay.

    PubMed

    Al-Thabaiti, Shaeel A; Ray, Suprakas Sinha; Basahel, Sulaiman Nassir; Mokhtar, Mohamed

    2015-03-01

    The processing and characterization of multifunctional nanobiocomposite of biodegradable poly[(butylene succinate)-co-adipate] (PBSA) and organically modified synthetic fluorine mica (OSFM) are reported. The nanobiocomposite of PBSA with OSFM was prepared using melt- blending, and the structure and morphology of the nanocomposite were characterized using X-ray diffraction and transmission electron microscopy. The mechanical and material properties measurements showed the concurrent improvement in temperature dependence storage modulus, tensile properties, gas barrier, and thermal stability of neat PBSA after nanocomposite formation. Such improved inherent properties along with the environmentally-friendly feature are expected to widen the use of PBSA for short-term food-packaging applications. PMID:26413685

  14. Crystal structure of (S)-2-amino-2-methyl­succinic acid

    PubMed Central

    Fujii, Isao

    2015-01-01

    The title compound, C5H9NO4, crystallized as a zwitterion. There is an intra­molecular N—H⋯O hydrogen bond involving the trans-succinic acid and the ammonium group, forming an S(6) ring motif. In the crystal, mol­ecules are linked by O—H⋯O hydrogen bonds, forming C(7) chains along the c-axis direction. The chains are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming sheets parallel to the bc plane. Further N—H⋯O hydrogen bonds link the sheets to form a three-dimensional framework. PMID:26594447

  15. Succinate dehydrogenase in Rhodopseudomonas sphaeroides: subunit composition and immunocross-reactivity with other related bacteria.

    PubMed Central

    Barassi, C A; Kranz, R G; Gennis, R B

    1985-01-01

    Antibodies were raised against the succinate dehydrogenase (SDH) present in the chromatophores of phototrophically grown Rhodopseudomonas sphaeroides. Crossed immunoelectrophoresis experiments indicated that the SDH present in the cytoplasmic membranes of heterotrophically grown R. sphaeroides is probably the same enzyme observed in the chromatophores. The enzyme was extracted by Triton X-100 in a form which consisted of only two subunits (molecular weight, 68,000 and 30,000) and was not associated with a cytochrome b. The antibodies directed against SDH from R. sphaeroides showed no immunocross-reactivity with SDH from phylogenetically related bacterial species, including Rhodopseudomonas capsulata, Paracoccus denitrificans, Rhodopseudomonas palustris, Rhodospirillum rubrum, and Rhodospirillum fulvum. Images PMID:3874866

  16. [Succinate dehydrogenase-deficient tumors--a novel mechanism of tumor formation].

    PubMed

    Miettinen, Markku

    2015-01-01

    Succinate dehydrogenase (SDH) is a heterotetrameric enzyme complex participating in the Krebs cycle and electron transfer of oxidative phosphorylation. These tumors, discovered during the past 15 years, often occur in young patients and include 15% of paragangliomas, 7% of gastric gastrointestinal stromal tumors (GISTs), and <1% of renal cell carcinomas and pituitary adenomas. SDH-deficient tumors have lost SDH complex activity via bi-allelic genomic losses or epigenetic silencing. This deficiency is oncogenic, activating pseudohypoxia signaling. SDH deficiency has to be suspected in the above-cited tumor types presenting at a young age. Immunohistochemical testing of tumor tissue for SDHB loss is diagnostic. PMID:26749909

  17. Structural properties of aqueous metoprolol succinate solutions. Density, viscosity, and refractive index at 311 K

    NASA Astrophysics Data System (ADS)

    Deosarkar, S. D.; Kalyankar, T. M.

    2013-06-01

    Density, viscosity and refractive index of aqueous solutions of metoprolol succinate of different concentrations (0.005-0.05 mol dm-3) were measured at 38°C. Apparent molar volume of resultant solutions were calculated and fitted to the Masson's equation and apparent molar volume at infinite dilution was determined graphically. Viscosity data of solutions has been fitted to the Jone-Dole equation and viscosity A- and B-coefficients were determined graphically. Physicochemical data obtained were discussed in terms of molecular interactions.

  18. Challenges in Catalytic Manufacture of Renewable Pyrrolidinones from Fermentation Derived Succinate

    SciTech Connect

    White, James F.; Holladay, Johnathan E.; Zacher, Alan H.; Frye, John G.; Werpy, Todd A.

    2014-09-05

    Fermentation derived succinic acid ammonium salt is an ideal precursor for manufacture of renewable N-methyl pyrrolidinone (NMP) or 2-pyrrolidinone (2P) via heterogeneous catalysis. However, there are many challenges to making this a practical reality. Chief among the challenges is avoiding catalyst poisoning by fermentation by- and co-products. Battelle / Pacific Northwest National Laboratory (PNNL) have developed an economically effective technology strategy for this purpose. The technology is a combination of purely thermal processing, followed by simple catalytic hydrogenation that together avoids catalyst poisoning from fermentation impurities and provides high selectivity and yields of NMP or 2P.

  19. Megestrol acetate for treatment of endometriosis.

    PubMed

    Schlaff, W D; Dugoff, L; Damewood, M D; Rock, J A

    1990-04-01

    Between 1977-1989, 29 women with symptomatic endometriosis were treated with megestrol acetate by the Johns Hopkins Division of Reproductive Endocrinology. All had previously received one or more alternative medical treatments for endometriosis, in each case discontinued because of poor response or development of unacceptable side effects. Treatment consisted of a daily dose of 40 mg megestrol acetate orally for up to 24 months. Disease-related symptoms (dysmenorrhea, noncyclic pelvic pain, and dyspareunia) were relieved in 86% of the subjects treated with an adequate course of therapy. Side effects were fairly well tolerated, although eight women discontinued treatment within 2 months and two others stopped the drug by 4 months. These preliminary findings suggest that megestrol acetate may be an effective treatment for patients with endometriosis, even those who have been unresponsive to other modes of therapy. PMID:2314784

  20. Identification of the flavoprotein of succinate dehydrogenase and aconitase as in vitro mitochondrial substrates of Fgr tyrosine kinase.

    PubMed

    Salvi, Mauro; Morrice, Nick A; Brunati, Anna Maria; Toninello, Antonio

    2007-12-11

    Overlooked until recently, mitochondrial protein phosphorylation is now emerging as a key post-translational mechanism in the regulation of mitochondrial functions. In particular, tyrosine phosphorylation represents a promising field to discover new mechanisms of bioenergetic regulation. Tyrosine kinases belonging to the Src kinase family have been observed in mitochondrial compartments, however their substrates are almost unknown. Here, we provide evidence that the flavoprotein of succinate dehydrogenase and aconitase are "in vitro" substrates of Fgr tyrosine kinase. Fgr phosphorylates flavoprotein of succinate dehydrogenase at Y535 and Y596 and aconitase at Y71, Y544 and Y665. The significance of these findings is discussed. PMID:17997986

  1. Investigating the thermostability of succinate: quinone oxidoreductase enzymes by direct electrochemistry at SWNTs-modified electrodes and FTIR spectroscopy

    PubMed Central

    Melin, Frederic; Noor, Mohamed R.; Pardieu, Elodie; Boulmedais, Fouzia; Banhart, Florian; Cecchini, Gary; Soulimane, Tewfik

    2015-01-01

    Succinate Quinone reductases (SQRs) are the enzymes which couple the oxidation of succinate and the reduction of quinones in the respiratory chain of prokaryotes and eukaryotes. We compare herein the temperature-dependent activity and structural stability of two SQRs, the first one from the mesophilic bacterium E. coli and the second one from the thermophilic bacterium T. thermophilus by a combined electrochemical and infrared spectroscopy approach. Direct electron transfer was achieved with the full membrane protein complexes at SWNTs-modified electrodes. The possible structural factors which contribute to the temperature-dependent activity of the enzymes and to the thermostability of the T. thermophiles SQR in particular, are discussed. PMID:25139263

  2. MW Spectroscopy Coupled with Ultrafast UV Laser Vaporization: Succinic Acid in the Gas Phase

    NASA Astrophysics Data System (ADS)

    Mendez, Estibaliz; Ecija, Patricia; Cocinero, Emilio J.; Castano, Fernando; Basterretxea, Francisco J.; Godfrey, Peter D.; McNaughton, Don; Jahn, Michaela K.; Nair, K. P. Rajappan; Grabow, Jens-Uwe

    2013-06-01

    Recent lab and field measurements have indicated critical roles of organic acids in enhancing new atmospheric aerosol formation. In order to understand the nucleation process, here we report an experimental and theoretical investigation of chemical structure of succinic acid. We have used the technique of Fourier Transform Microwave Spectroscopy (FTMW). Succinic acid was vaporized by UV ultrafast laser ablation to suppress thermal decomposition processes^a and seeded into an expanding stream of Ne forming a supersonic jet. The rotational spectrum detected the presence of a single most stable conformation in the cm- mm- wave regions for which accurate rotational and centrifugal distortion parameters have been determined. The study was extended to all monosubstituted isotopic species (^{13}C, ^{18}O, D(O)), which were positively identified, leading to an accurate determination of the effective and substitution structures of the molecule. The experimental study was supplemented by ab initio (MP2) and DFT (M06-2X and B3LYP) calculations. ^{a} E. J. Cocinero, A. Lesarri, P. écija, F. J. Basterretxea, J. U. Grabow, J. A. Fernández and F. Castaño, Angew. Chem. Int. Ed., 51, 3119-3124, 2012.

  3. Review of succinate dehydrogenase-deficient renal cell carcinoma with focus on clinical and pathobiological aspects.

    PubMed

    Kuroda, N; Yorita, K; Nagasaki, M; Harada, Y; Ohe, C; Jeruc, J; Raspollini, M R; Michal, M; Hes, O; Amin, M B

    2016-03-01

    Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) was first identified in 2004 and has been integrated into the 2016 WHO classification of RCC. Succinate dehydrogenase (SDH) is an enzyme complex composed of four protein subunits (SDHA, SDHB, SDHC and SDHD). The tumor which presents this enzyme mutation accounts for 0.05 to 0.2% of all renal carcinomas. Multiple tumors may occur in approximately 30% of affected patients. SDHB-deficient RCC is the most frequent, and the tumor histologically consists of cuboidal cells with eosinophilic cytoplasm, vacuolization, flocculent intracytoplasmic inclusion and indistinct cell borders. Ultrastructurally, the tumor contains abundant mitochondria. Immunohistochemically, tumor cells are positive for SDHA, but negative for SDHB in SDHB-, SDHC- and SDHD-deficient RCCs. However, SDHA-deficient RCC shows negativity for both SDHA and SDHB. In molecular genetic analyses, a germline mutation in the SDHB, SDHC or SDHD gene (in keeping with most patients having germline mutations in an SDH gene) has been identified in patients with or without a family history of renal tumors, paraganglioma/pheochromocytoma or gastrointestinal stromal tumor. While most tumors are low grade, some tumors may behave in an aggressive fashion, particularly if they are high nuclear grade, and have coagulative necrosis or sarcomatoid differentiation. PMID:27179267

  4. Conformation of succinic acid: its pH dependence by Licry-NMR analysis

    NASA Astrophysics Data System (ADS)

    Chidichimo, G.; Formoso, P.; Golemme, A.; Imbardelli, D.

    The conformations of fully protonated (H2SA), fully deprotonated (SA=) and monoprotonated (HSA-) succinic acid have been investigated by means of nuclear magnetic resonance spectroscopy in liquid crystal mesophases (Licry-NMR). H-H and 13C-H direct dipolar couplings have been determined by measuring 1H-NMR and 13C-NMR spectra from quaternary nematic-lyotropic solutions of myristyltrimethylammonium bromide (MTAB), decanol, deuterated water and succinic acid (in each of its three different protonated forms). Direct dipolar couplings have been used to investigate the conformational equilibrium of the molecule in its three different protonation forms. Data could be interpreted in terms of a single conformation for each of the investigated forms. The dihedral angle between the H3-C5'-C5 and the C5'-C5-H1 planes gradually increases when going from the fully protonated H2SA species to the SA= ions. Our findings are different from those obtained by other authors by analysis of Jij couplings. In that case an equilibrium conformation between the gauche and trans conformers had been obtained.

  5. Succinate Functionalization of Hyperbranched Polyglycerol-Coated Magnetic Nanoparticles as a Draw Solute During Forward Osmosis.

    PubMed

    Yang, Hee-Man; Choi, Hye Min; Jang, Sung-Chan; Han, Myeong Jin; Seo, Bum-Kyoung; Moon, Jei-Kwon; Lee, Kune-Woo

    2015-10-01

    Hyperbranched polyglycerol-coated magnetic nanoparticles (SHPG-MNPs) were functionalized with succinate groups to form a draw solute for use in a forward osmosis (FO). After the one-step synthesis of hyperbranched polyglycerol-coated magnetic nanoparticles (HPG-MNPs), the polyglycerol groups on the surfaces of the HPG-MNPs were functionalized with succinic anhydride moieties. The resulting SHPG-MNPs showed no change of size and magnetic property compared with HPG-MNPs and displayed excellent dispersibility in water up to the concentration of 400 g/L. SHPG-MNPs solution showed higher osmotic pressure than that of HPG-MNPs solution due to the presence of surface carboxyl groups in SHPG-MNPs and could draw water from a feed solution across an FO membrane without any reverse draw solute leakage during FO process. Moreover, the water flux remained nearly constant over several SHPG-MNP darw solute regeneration cycles applied to the ultrafiltration (UF) process. The SHPG-MNPs demonstrate strong potential for use as a draw solute in FO processes. PMID:26726503

  6. Controlled release floating multiparticulates of metoprolol succinate by hot melt extrusion.

    PubMed

    Malode, Vilas N; Paradkar, Anant; Devarajan, Padma V

    2015-08-01

    We present hot melt extrusion (HME) for the design of floating multiparticulates. Metoprolol succinate was selected as the model drug. Our foremost objective was to optimize the components Eudragit(®) RS PO, polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) to balance both buoyancy and controlled release. Gas generated by sodium bicarbonate in acidic medium was trapped in the polymer matrix to enable floating. Eudragit(®) RS PO and PEO with sodium bicarbonate resulted in multiparticulates which exhibited rapid flotation within 3 min but inadequate total floating time (TFT) of 3h. Addition of HPMC to the matrix did not affect floating lag time (FLT), moreover TFT increased to more than 12h with controlled release of metoprolol succinate. Floating multiparticulates exhibited t50% of 5.24h and t90% of 10.12h. XRD and DSC analysis revealed crystalline state of drug while FTIR suggested nonexistence of chemical interaction between the drug and the other excipients. The assay, FLT, TFT and the drug release of the multiparticulates were unchanged when stored at 40°C/75%RH for 3 months confirming stability. We present floating multiparticulates by HME which could be extrapolated to a range of other drugs. Our approach hence presents platform technology for floating multiparticulates. PMID:26142246

  7. α-Tocopherol succinate improves encapsulation and anticancer activity of doxorubicin loaded in solid lipid nanoparticles.

    PubMed

    Oliveira, Mariana S; Mussi, Samuel V; Gomes, Dawidson A; Yoshida, Maria Irene; Frezard, Frederic; Carregal, Virgínia M; Ferreira, Lucas A M

    2016-04-01

    This work aimed to develop solid lipid nanoparticles (SLN) co-loaded with doxorubicin and α-tocopheryl succinate (TS), a succinic acid ester of α-tocopherol that exhibits anticancer actions, evaluating the influence of TS on drug encapsulation efficiency. The SLN were characterized for size, zeta potential, entrapment efficiency (EE), and drug release. Studies of in vitro anticancer activity were also conducted. The EE was significantly improved from 30 ± 1% to 96 ± 2% for SLN without and with TS at 0.4%, respectively. In contrast, a reduction in particle size from 298 ± 1 to 79 ± 1 nm was observed for SLN without and with TS respectively. The doxorubicin release data show that SLN provide a controlled drug release. The in vitro studies showed higher cytotoxicity for doxorubicin-TS-loaded SLN than for free doxorubicin in breast cancer cells. These findings suggest that TS-doxorubicin-loaded SLN is a promising alternative for the treatment of cancer. PMID:26764108

  8. Multifunctional essentiality of succinate metabolism in adaptation to hypoxia in Mycobacterium tuberculosis

    PubMed Central

    Eoh, Hyungjin; Rhee, Kyu Y.

    2013-01-01

    Mycobacterium tuberculosis is a chronic, facultative intracellular pathogen that spends the majority of its decades-long life cycle in a non- or slowly replicating state. However, the bacterium remains poised to resume replicating so that it can transmit itself to a new host. Knowledge of the metabolic adaptations used to facilitate entry into and exit from nonreplicative states remains incomplete. Here, we apply 13C-based metabolomic profiling to characterize the activity of M. tuberculosis tricarboxylic acid cycle during adaptation to and recovery from hypoxia, a physiologically relevant condition associated with nonreplication. We show that, as M. tuberculosis adapts to hypoxia, it slows and remodels its tricarboxylic acid cycle to increase production of succinate, which is used to flexibly sustain membrane potential, ATP synthesis, and anaplerosis, in response to varying degrees of O2 limitation and the presence or absence of the alternate electron acceptor nitrate. This remodeling is mediated by the bifunctional enzyme isocitrate lyase acting in a noncanonical role distinct from fatty acid catabolism. Isocitrate lyase-dependent production of succinate affords M. tuberculosis with a unique and bioenergetically efficient metabolic means of entry into and exit from hypoxia-induced quiescence. PMID:23576728

  9. Freeze drying: exploring potential in development of orodispersible tablets of sumatriptan succinate.

    PubMed

    Gugulothu, Dalapathi; Desai, Preshita; Pandharipande, Pranav; Patravale, Vandana

    2015-03-01

    The present investigation is aimed at development and characterization of sumatriptan succinate orodispersible tablets (ODTs) prepared by freeze drying technology. The tablet excipients were screened and the composition was optimized based on parameters which involved general appearance, tablet size and shape, uniformity of weight, mechanical properties, surface pH, moisture analysis, drug content, wetting time, in vitro and in vivo disintegration time. Furthermore, fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron micrograph of cross-section of the tablet and in vitro dissolution studies were performed. Studies revealed that formulation containing gelatin-mannitol (3.75% w/v and 3.5% w/v, respectively) with camphor as a volatile pore forming agent exhibited superior properties with disintegration time of less than 10 s. Furthermore, in vitro release studies revealed 90% release of drug from developed dosage form within 10 min, thus suggesting rapid drug dissolution followed by faster onset of action, which forms a strong rationale for development of ODTs of sumatriptan succinate. The developed technology is simple, which involves few steps and can be easily scaled up. Thus, it holds enormous potential for commercial exploitation. PMID:24384027

  10. Hypromellose succinate-crosslinked chitosan hydrogel films for potential wound dressing.

    PubMed

    Jiang, Qiong; Zhou, Wei; Wang, Jun; Tang, Rupei; Zhang, Di; Wang, Xin

    2016-10-01

    The objective of this study was to develop novel hydrogel films based on carboxyl-modified hypromellose-crosslinked chitosan for potential wound dressing. Hypromellose (HPMC) was grafted with succinic acid to yield hypromellose succinate (HPMCS), and then the reinforced hydrogel films of HPMCS-crosslinked chitosan (HPMCS-CS) were prepared through amide bond formation using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N- hydroxysuccinimide (NHS) as a catalyst. Compared to that of blend film, mechanical properties of HPMCS-CS hydrogel films were significantly enhanced both in dry and swollen state. To assess the applicability of HPMCS-CS hydrogel films as wound dressing, the swelling behavior, water vapor transmission rate (WVTR), oxygen permeability, biocompatibility (cytotoxicity and hemolysis), in vitro drug release and bactericidal properties were analyzed. The results indicated that HPMCS-CS hydrogel films with good biocompatibility possess high swelling ratio, proper WVTR, and oxygen permeability, which might accelerate tissue regeneration. Meanwhile, gentamycin sulfate release from drug-loaded HPMCS-CS hydrogel films were sustained, which would help to protect wound from infection. PMID:27222285

  11. Solvation of Dimethyl Succinate in a Sodium Hydroxide Aqueous Solution. A Computational Study

    SciTech Connect

    Sun, Xiuquan; Chang, Tsun-Mei; Cao, Yang; Niwayama, Satomi; Hase, William L.; Dang, Liem X.

    2009-05-07

    Molecular dynamics simulations were carried out to study dimethyl-succinate/water/NaOH solutions. The potential of mean force method is used to determine the transport mechanism of a dimethyl-succinate (a diester) molecule across the aqueous/vapor interface. The computed number density profiles show a strong propensity for the diester molecules to congregate at the interface with the solubility of the diester increasing with increasing NaOH concentration. It is observed that the major contribution to the interfacial solvation free energy minimum is from van der Waals interactions. Thus, even at higher NaOH concentrations, the increasing electrostatic interaction between the diester and ions is not large enough to overcome the Lennard-Jones (LJ) interactions to favor the solvation of diester in bulk solutions. The calculated solvation free energies are found to be -2.6 ~ -3.5 kcal/mol in variant concentrations of NaOH aqueous solutions. These values are in qualitative agreement with the corresponding experimental measurements. The computed surface potential indicates that the contribution of diester molecules to the total surface potential is about 25%, with the major contribution from interfacial water molecules. This work was supported by the US Department of Energy (DOE) Office of Basic Energy Sciences, Chemical Sciences program. Pacific Northwest National Laboratory is operated by Battelle for DOE.

  12. Guar gum succinate as a carrier for colon-specific drug delivery.

    PubMed

    Seeli, D Sathya; Prabaharan, M

    2016-03-01

    A novel type of pH-sensitive colon-specific controlled drug delivery carrier based on guar gum succinate (GGS) was prepared by reacting guar gum (GG) with succinic anhydride (SA) in the presence of 4-dimethylaminopyridine (DMAP). The formation of GGS was confirmed by FT-IR and (1)H NMR and characterized using XRD techniques. GGS microparticles with 460-740 μm in size were prepared using sodium trimetaphosphate (STMP) as a cross-linking agent. The size and morphologies of GGS microparticles were assessed by scanning electron microscopy (SEM). The swelling degree of the GGS microparticles was found to be higher in pH 7.4 than in pH 1.2. In addition, GGS microparticles showed a pH dependent drug release profile when compared to the GG microparticles. The MTT assay revealed that there is no apparent cytotoxicity of GGS against a mouse mesenchymal stem cell line at a concentration range of 0-200 μg/ml. These results confirm that GGS could be used as a carrier for colon-specific drug delivery. PMID:26675135

  13. Saturation transfer difference NMR studies on substrates and inhibitors of succinic semialdehyde dehydrogenases

    SciTech Connect

    Jaeger, Martin Rothacker, Boris; Ilg, Thomas

    2008-08-01

    Saturation transfer difference (STD) NMR experiments on Escherichia coli and Drosophila melanogaster succinic semialdehyde dehydrogenase (SSADH, EC1.2.1.24) suggest that only the aldehyde forms and not the gem-diol forms of the specific substrate succinic semialdehyde (SSA), of selected aldehyde substrates, and of the inhibitor 3-tolualdehyde bind to these enzymes. Site-directed mutagenesis of the active site cysteine311 to alanine in D. melanogaster SSADH leads to an inactive product binding both SSA aldehyde and gem-diol. Thus, the residue cysteine311 is crucial for their discrimination. STD experiments on SSADH and NAD{sup +}/NADP{sup +} indicate differential affinity in agreement with the respective cosubstrate properties. Epitope mapping by STD points to a strong interaction of the NAD{sup +}/NADP{sup +} adenine H2 proton with SSADH. Adenine H8, nicotinamide H2, H4, and H6 also show STD signals. Saturation transfer to the ribose moieties is limited to the anomeric protons of E. coli SSADH suggesting that the NAD{sup +}/NADP{sup +} adenine and nicotinamide, but not the ribose moieties are important for the binding of the coenzymes.

  14. Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor.

    PubMed

    Killian, J Keith; Kim, Su Young; Miettinen, Markku; Smith, Carly; Merino, Maria; Tsokos, Maria; Quezado, Martha; Smith, William I; Jahromi, Mona S; Xekouki, Paraskevi; Szarek, Eva; Walker, Robert L; Lasota, Jerzy; Raffeld, Mark; Klotzle, Brandy; Wang, Zengfeng; Jones, Laura; Zhu, Yuelin; Wang, Yonghong; Waterfall, Joshua J; O'Sullivan, Maureen J; Bibikova, Marina; Pacak, Karel; Stratakis, Constantine; Janeway, Katherine A; Schiffman, Joshua D; Fan, Jian-Bing; Helman, Lee; Meltzer, Paul S

    2013-06-01

    Gastrointestinal stromal tumors (GIST) harbor driver mutations of signal transduction kinases such as KIT, or, alternatively, manifest loss-of-function defects in the mitochondrial succinate dehydrogenase (SDH) complex, a component of the Krebs cycle and electron transport chain. We have uncovered a striking divergence between the DNA methylation profiles of SDH-deficient GIST (n = 24) versus KIT tyrosine kinase pathway-mutated GIST (n = 39). Infinium 450K methylation array analysis of formalin-fixed paraffin-embedded tissues disclosed an order of magnitude greater genomic hypermethylation relative to SDH-deficient GIST versus the KIT-mutant group (84.9 K vs. 8.4 K targets). Epigenomic divergence was further found among SDH-mutant paraganglioma/pheochromocytoma (n = 29), a developmentally distinct SDH-deficient tumor system. Comparison of SDH-mutant GIST with isocitrate dehydrogenase-mutant glioma, another Krebs cycle-defective tumor type, revealed comparable measures of global hypo- and hypermethylation. These data expose a vital connection between succinate metabolism and genomic DNA methylation during tumorigenesis, and generally implicate the mitochondrial Krebs cycle in nuclear epigenomic maintenance. PMID:23550148

  15. In-vitro characterization of buccal iontophoresis: the case of sumatriptan succinate.

    PubMed

    Telò, Isabella; Tratta, Elena; Guasconi, Barbara; Nicoli, Sara; Pescina, Silvia; Govoni, Paolo; Santi, Patrizia; Padula, Cristina

    2016-06-15

    Buccal administration of sumatriptan succinate might be an interesting alternative to the present administration routes, due to its non-invasiveness and rapid onset of action, but because of its low permeability, a permeation enhancement strategy is required. The aim of this work was then to study, in-vitro, buccal iontophoresis of sumatriptan succinate. Permeation experiments were performed in-vitro across pig esophageal epithelium, a recently proposed model of human buccal mucosa, using vertical diffusion cells. The iontophoretic behavior of the tissue was characterized by measuring its isoelectric point (Na(+) transport number and the electroosmotic flow of acetaminophen determination) and by evaluating tissue integrity after current application. The results obtained confirm the usefulness of pig esophageal epithelium as an in-vitro model membrane for buccal drug delivery. The application of iontophoresis increased sumatriptan transport, proportionally to the current density applied, without tissue damage: electrotransport was the predominant mechanism. Integrating the results of the present work with literature data on the transport of other molecules across the buccal mucosa and across the skin, we can draw a general conclusion: the difference in passive transport across buccal mucosa and across the skin is influenced by permeant lipophilicity and by the penetration pathway. Finally, buccal iontophoretic administration of sumatriptan allows to administer 6mg of the drug in 1h, representing a promising alternative to the current administration routes. PMID:27113869

  16. Chemical synthesis of fully biomass-based poly(butylene succinate) from inedible-biomass-based furfural and evaluation of its biomass carbon ratio.

    PubMed

    Tachibana, Yuya; Masuda, Takashi; Funabashi, Masahiro; Kunioka, Masao

    2010-10-11

    We have produced fully biomass-based poly(butylene succinate) (PBS) from furfural produced from inedible agricultural cellulosic waste. Furfural was oxidized to give fumaric acid. Fumaric acid was hydrogenated under high pressure with a palladium-rhenium/carbon catalyst to give 1,4-butanediol, and with a palladium/carbon catalyst to give succinic acid. Dimethyl succinate was synthesized from fumaric acid by esterification and hydrogenation under normal pressure. Fully biomass-based PBS was obtained by polycondensation of biomass-based 1,4-butanediol and biomass-based succinic acid or dimethyl succinate. The biomass carbon ratio calculated from (14)C concentrations measured by accelerator mass spectroscopy (AMS) verified that the PBS obtained in this study contained only biomass carbon. The polycondensation of biomass-based 1,4-butanediol and petroleum-based terephthalic acid or dimethyl terephthalate gave partially biomass-based poly(butylene terephthalate), which is an engineering plastic. PMID:20815381

  17. Synthesis of Cellulose Acetate from Cotton Byproducts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cotton burr and cottonseed hull are relatively inexpensive cotton byproducts. In an effort to derive greater value out of these natural renewable materials, we have succeeded in converting part of them into cellulose acetate without prior chemical breakdown or physical separation of cellulose, ligni...

  18. Advanced Colloids Experiment (ACE-T1)

    NASA Technical Reports Server (NTRS)

    Meyer, William V.; Sicker, Ron; Brown, Dan; Eustace, John

    2015-01-01

    Increment 45 - 46 Science Symposium presentation of Advanced Colloids Experiment (ACE-T1) to RPO. The purpose of this event is for Principal Investigators to present their science objectives, testing approach, and measurement methods to agency scientists, managers, and other investigators.

  19. 21 CFR 184.1185 - Calcium acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Calcium acetate. 184.1185 Section 184.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS...

  20. 21 CFR 556.380 - Melengestrol acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Melengestrol acetate. 556.380 Section 556.380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs §...

  1. Heat Bonding of Irradiated Ethylene Vinyl Acetate

    NASA Technical Reports Server (NTRS)

    Slack, D. H.

    1986-01-01

    Reliable method now available for joining parts of this difficult-tobond material. Heating fixture encircles ethylene vinyl acetate multiplesocket part, providing heat to it and to tubes inserted in it. Fixtures specially designed to match parts to be bonded. Tube-and-socket bonds made with this technique subjected to tensile tests. Bond strengths of 50 percent that of base material obtained consistently.

  2. 21 CFR 522.1881 - Prednisolone acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Prednisolone acetate. 522.1881 Section 522.1881 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... used as supportive therapy pre- and postoperatively and for various stress conditions...

  3. Fragrance material review on phenethyl acetate.

    PubMed

    McGinty, D; Vitale, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of phenethyl acetate when used as a fragrance ingredient is presented. Phenethyl acetate is a member of the fragrance structural group aryl alkyl alcohol simple acid esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for phenethyl acetate were evaluated, then summarized, and includes: physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, toxicokinetics, repeated dose, genotoxicity, and carcinogenicity data. A safety assessment of the entire AAASAE will be published simultaneously with this document. Please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances. PMID:22414644

  4. Reactions of germanium tetrahalides with ketene acetals

    SciTech Connect

    Efimova, I.V.; Kazankova, M.A.; Lutsenko, I.F.

    1985-05-01

    Recently, the authors reported that alkyl vinyl ethers and terminal alkynes are readily germylated by germanium tetrahalides in the presence of a tertiary amine. To extend the range of applicability of this reaction and to obtain additional information on its mechanism, the authors study reactions of ketene acetals with germanium tetrachloride and tetrabromide in the presence of triethylamine.

  5. 21 CFR 184.1721 - Sodium acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium acetate. 184.1721 Section 184.1721 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS §...

  6. Process for the preparation of vinyl acetate

    DOEpatents

    Tustin, G.C.; Zoeller, J.R.; Depew, L.S.

    1998-02-17

    This invention pertains to the preparation of vinyl acetate by contacting within a contact zone a mixture of ketene and acetaldehyde with an acid catalyst at about one bar pressure and between about 85 and 200 C and removing the reaction products from the contact zone.

  7. Process for the preparation of vinyl acetate

    DOEpatents

    Tustin, Gerald Charles; Zoeller, Joseph Robert; Depew, Leslie Sharon

    1998-01-01

    This invention pertains to the preparation of vinyl acetate by contacting within a contact zone a mixture of ketene and acetaldehyde with an acid catalyst at about one bar pressure and between about 85.degree. and 200.degree. C. and removing the reaction products from the contact zone.

  8. Phenyl Acetate Preparation from Phenol and Acetic Acid: Reassessment of a Common Textbook Misconception.

    ERIC Educational Resources Information Center

    Hocking, M. B.

    1980-01-01

    Reassesses a common textbook misconception that "...phenols cannot be esterified directly." Results of experiments are discussed and data tables provided of an effective method for the direct preparation of phenyl acetate. (CS)

  9. Easy preparation of enantiomerically enriched heteroaromatic alcohols through lipase-catalyzed acylation with succinic anhydride under unconventional activation.

    PubMed

    Melais, Nedjma; Boukachabia, Mourad; Aribi-Zouioueche, Louisa; Riant, Olivier

    2015-08-01

    This study reports the lipase-catalyzed resolution of heteroaromatic secondary alcohols by succinic anhydride under different activation conditions by convenient procedure with succinic anhydride. The effects of succinic anhydride and the nature of the heteroatom are discussed in standard conditions in the kinetic resolution with lipases. The results recorded under microwave activation and ultrasonication is compared. (R)-4-chromanol was obtained in optically pure form (ee > 99%) with a high selectivity E > 200 by Pseudomonas cepacia lipase (PCL) in diethyl ether, using microwave radiation and under ultrasonication. The reaction time is reduced compared to the conventional heating with a better control of the selectivity of the lipase PCL. A significant effect of the nature of the heteroatoms on the reactivity and selectivity of the lipase with succinic anhydride has been disclosed, regardless the conditions of activation. This method proved to be clean, fast, interesting alternative, and facilitates the use of a cyclic anhydride, by microwave or ultrasound especially with secondary alcohols. The process is a valuable prerequisite for the preparative scale production of enantiomerically heteroaromatic alcohols in sustainable chemistry. PMID:25957778

  10. Capture of carbon dioxide from ethanol fermentation by liquid absorption for use in biological production of succinic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously it was shown that the gas produced in an ethanol fermentor using either corn or barley as feedstock could be sparged directly into an adjacent fermentor using Escherichia coli AFP184 to provide the CO2 required for succinic acid production. In the present investigation it has been demons...

  11. Capture of carbon dioxide from ethanol fermentation by liquid absorption for use in biological production of succinic acid.

    PubMed

    Nghiem, Nhuan P; Senske, Gerard E

    2015-02-01

    Previously, it was shown that the gas produced in an ethanol fermentor using either corn or barley as feedstock could be sparged directly into an adjacent fermentor as a feedstock for succinic acid fermentation using Escherichia coli AFP184. In the present investigation, it was demonstrated that the CO2 produced in a corn ethanol fermentor could be absorbed in a base solution and the resultant carbonate solution used both for pH control and supply of the CO2 requirement in succinic acid fermentation. Thus, the CO2 produced in a 5-L corn mash containing 30 wt% total solids was absorbed in a packed column containing 2 L of either 5 M NaOH, 5 M KOH, or 15 wt% NH4OH, and the resultant carbonate solutions were used for pH control in a succinic acid fermentor. The results obtained indicated no significant differences between succinic acid production in these experiments and when 2.5 M solutions of Na2CO3, K2CO3, and (NH4)2CO3 from commercial sources were used. In a commercial setting, the demonstrated capture of CO2 in liquid form will allow transportation of the carbonate solutions to locations not in the immediate vicinity of the ethanol plant, and excess carbonate salts can also be recovered as value-added products. PMID:25448631

  12. A novel mutation in the succinate dehydrogenase subunit D gene in siblings with the hereditary paraganglioma–pheochromocytoma syndrome

    PubMed Central

    Oakley, Gerard J; Yip, Linwah; Coyne, Christopher; Rangaswamy, Balasubramanya; Dixit, Sanjay B

    2014-01-01

    Germline mutations in the succinate dehydrogenase complex subunit D gene are now known to be associated with hereditary paraganglioma–pheochromocytoma syndromes. Since the initial succinate dehydrogenase complex subunit D gene mutation was identified about a decade ago, more than 131 unique variants have been reported. We report the case of two siblings presenting with multiple paragangliomas and pheochromocytomas; they were both found to carry a mutation in the succinate dehydrogenase complex subunit D gene involving a substitution of thymine to guanine at nucleotide 236 in exon 3. This particular mutation of the succinate dehydrogenase complex subunit D gene has only been reported in one previous patient in Japan; this is, therefore, the first report of this pathogenic mutation in siblings and the first report of this mutation in North America. With continued screening of more individuals, we will be able to create a robust mutation database that can help us understand disease patterns associated with particular variants and may be a starting point in the development of new therapies for familial paraganglioma syndromes. PMID:27489656

  13. Papyriferic acid, an antifeedant triterpene from birch trees, inhibits succinate dehydrogenase from liver mitochondria.

    PubMed

    McLean, Stuart; Richards, Stephen M; Cover, Siow-Leng; Brandon, Sue; Davies, Noel W; Bryant, John P; Clausen, Thomas P

    2009-10-01

    Papyriferic acid (PA) is a triterpene that is secreted by glands on twigs of the juvenile ontogenetic phase of resin producing tree birches (e.g., Betula neoalaskana, B. pendula) and that deters browsing by mammals such as the snowshoe hare (Lepus americanus). We investigated the pharmacology of PA as a first step in understanding its antifeedant effect. After oral administration to rats, PA and several metabolites were found in feces but not urine, indicating that little was absorbed systemically. Metabolism involved various combinations of hydrolysis of its acetyl and malonyl ester groups, and hydroxylation of the terpene moiety. The presence of a malonyl group suggested a possible interaction with succinate dehydrogenase (SDH), a mitochondrial enzyme known to be competitively inhibited by malonic acid. The effect of PA on the oxidation of succinate by SDH was examined in mitochondrial preparations from livers of ox, rabbit, and rat. In all three species, PA was a potent inhibitor of SDH. Kinetic analysis indicated that, unlike malonate, PA acted by an uncompetitive mechanism, meaning that it binds to the enzyme-substrate complex. The hydrolysis product of PA, betulafolienetriol oxide, was inactive on SDH. Overall, the evidence suggests that PA acts as the intact molecule and interacts at a site other than the succinate binding site, possibly binding to the ubiquinone sites on complex II. Papyriferic acid was potent (K(iEIS) ranged from 25 to 45 microM in the three species) and selective, as malate dehydrogenase was unaffected. Although rigorous proof will require further experiments, we have a plausible mechanism for the antifeedant effect of PA: inhibition of SDH in gastrointestinal cells decreases mitochondrial energy production resulting in a noxious stimulus, 5-HT release, and sensations of nausea and discomfort. There is evidence that the co-evolution of birches and hares over a large and geographically-diverse area in Northern Europe and America has

  14. 21 CFR 582.5892 - a-Tocopherol acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5892 a-Tocopherol acetate. (a) Product. a-Tocopherol acetate. (b) Conditions of use....

  15. Expression of acetate permease-like (apl) genes in subsurface communities of Geobacter species under fluctuating acetate concentrations

    SciTech Connect

    Elifantz, H.; N'Guessan, L.A.; Mouser, P.J.; Williams, K H.; Wilkins, M J.; Risso, C.; Holmes, D.E.; Long, P.E.; Lovley, D.R.

    2010-03-01

    The addition of acetate to uranium-contaminated aquifers in order to stimulate the growth and activity of Geobacter species that reduce uranium is a promising in situ bioremediation option. Optimizing this bioremediation strategy requires that sufficient acetate be added to promote Geobacter species growth. We hypothesized that under acetate-limiting conditions, subsurface Geobacter species would increase the expression of either putative acetate symporters genes (aplI and aplII). Acetate was added to a uranium-contaminated aquifer (Rifle, CO) in two continuous amendments separated by 5 days of groundwater flush to create changing acetate concentrations. While the expression of aplI in monitoring well D04 (high acetate) weakly correlated with the acetate concentration over time, the transcript levels for this gene were relatively constant in well D08 (low acetate). At the lowest acetate concentrations during the groundwater flush, the transcript levels of aplII were the highest. The expression of aplII decreased 2-10-fold upon acetate reintroduction. However, the overall instability of acetate concentrations throughout the experiment could not support a robust conclusion regarding the role of apl genes in response to acetate limitation under field conditions, in contrast to previous chemostat studies, suggesting that the function of a microbial community cannot be inferred based on lab experiments alone.

  16. Expression of Acetate Permease-like (apl) Genes in Subsurface Communities of Geobacter Species Under Fluctuating Acetate Concentrations

    SciTech Connect

    Elifantz, H; N'Guessan, A L; Mouser, Paula; Williams, Kenneth H; Wilkins, Michael J; Risso, Carla; Holmes, Dawn; Long, Philip E; Lovley, Derek R

    2010-09-01

    The addition of acetate to uranium-contaminated aquifers in order to stimulate the growth and activity of Geobacter species that reduce uranium is a promising in situ bioremediation option. Optimizing this bioremediation strategy requires that sufficient acetate be added to promote Geobacter species growth. We hypothesized that under acetate-limiting conditions, subsurface Geobacter species would increase the expression of either putative acetate symporters genes (aplI and aplII). Acetate was added to a uranium-contaminated aquifer (Rifle, CO) in two continuous amendments separated by 5 days of groundwater flush to create changing acetate concentrations. While the expression of aplI in monitoring well D04 (high acetate) weakly correlated with the acetate concentration over time, the transcript levels for this gene were relatively constant in well D08 (low acetate). At the lowest acetate concentrations during the groundwater flush, the transcript levels of aplII were the highest. The expression of aplII decreased 2–10-fold upon acetate reintroduction. However, the overall instability of acetate concentrations throughout the experiment could not support a robust conclusion regarding the role of apl genes in response to acetate limitation under field conditions, in contrast to previous chemostat studies, suggesting that the function of a microbial community cannot be inferred based on lab experiments alone.

  17. Separating acetic acid from furol (furfural) by electrodialysis method

    SciTech Connect

    Guan, S.F.; Li, C.S. Ye, S.T.; Shen, S.Y.; Wang, Y.T.; Yu, S.H.

    1981-01-01

    Furfural production by hydrolysis of fibrous plant materials is accompanied by formation of acetic acid in amounts depending on the material used. The amount of acetic formed in the hydrolysis of the fruit shell of oil-tea camellia (Camellia oleosa) (an oilseed-bearing tree) is equal to the amount of furfural. The acetic acid can be separated from the furfural and concentrated to 10% by electrodialysis. A smaller amount of furfural is separated with acetic acid.

  18. Cyproterone acetate in treatment of precocious puberty.

    PubMed Central

    Kauli, R; Pertzelan, A; Prager-Lewin, R; Grünebaum, M; Laron, Z

    1976-01-01

    Twenty-nine children (23 girls, 6 boys) with precocious puberty were treated with cyproterone acetate for various periods of time ranging from 6 months to 3 years 4 months. They received an oral dose ranging from 70-150 mg/m2 per day, or an intramuscular depot injection once a fortnight or once a month at a dose ranging from 107-230 mg/m2. Both forms of therapy were found to suppress the signs of sexual maturation, but the oral form proved to be superior. Only the younger patients with a bone age under 11 years showed a beneficial effect upon linear growth and bone maturation. No side effects were noted, but additional advantageous effects upon behaviour and sociability were. It is concluded that at present cyproterone acetate by mouth is the drug of choice in the treatment of precocious puberty. The treatment should be initiated as early as possible to attain maximum benefit. PMID:952553

  19. Facile hydrolysis and alcoholysis of palladium acetate.

    PubMed

    Bedford, Robin B; Bowen, John G; Davidson, Russell B; Haddow, Mairi F; Seymour-Julen, Annabelle E; Sparkes, Hazel A; Webster, Ruth L

    2015-05-26

    Palladium(II) acetate is readily converted into [Pd3 (μ(2) -OH)(OAc)5 ] (1) in the presence of water in a range of organic solvents and is also slowly converted in the solid state. Complex 1 can also be formed in nominally anhydrous solvents. Similarly, the analogous alkoxide complexes [Pd3 (μ(2) -OR)(OAc)5 ] (3) are easily formed in solutions of palladium(II) acetate containing a range of alcohols. An examination of a representative Wacker-type oxidation shows that the Pd-OH complex 1 and a related Pd-oxo complex 4 can be excluded as potential catalytic intermediates in the absence of exogenous water. PMID:25865439

  20. Essentiality of Succinate Dehydrogenase in Mycobacterium smegmatis and Its Role in the Generation of the Membrane Potential Under Hypoxia

    PubMed Central

    Pecsi, Ildiko; Hards, Kiel; Ekanayaka, Nandula; Berney, Michael; Hartman, Travis; Jacobs, William R.

    2014-01-01

    ABSTRACT Succinate:quinone oxidoreductase (Sdh) is a membrane-bound complex that couples the oxidation of succinate to fumarate in the cytoplasm to the reduction of quinone to quinol in the membrane. Mycobacterial species harbor genes for two putative sdh operons, but the individual roles of these two operons are unknown. In this communication, we show that Mycobacterium smegmatis mc2155 expresses two succinate dehydrogenases designated Sdh1 and Sdh2. Sdh1 is encoded by a five-gene operon (MSMEG_0416-MSMEG_0420), and Sdh2 is encoded by a four-gene operon (MSMEG_1672-MSMEG_1669). These two operons are differentially expressed in response to carbon limitation, hypoxia, and fumarate, as monitored by sdh promoter-lacZ fusions. While deletion of the sdh1 operon did not yield any growth phenotypes on succinate or other nonfermentable carbon sources, the sdh2 operon could be deleted only in a merodiploid background, demonstrating that Sdh2 is essential for growth. Sdh activity and succinate-dependent proton pumping were detected in cells grown aerobically, as well as under hypoxia. Fumarate reductase activity was absent under these conditions, indicating that neither Sdh1 nor Sdh2 could catalyze the reverse reaction. Sdh activity was inhibited by the Sdh inhibitor 3-nitroproprionate (3NP), and treatment with 3NP dissipated the membrane potential of wild-type or Δsdh1 mutant cells under hypoxia but not that of cells grown aerobically. These data imply that Sdh2 is the generator of the membrane potential under hypoxia, an essential role for the cell. PMID:25118234

  1. Co-expression of phosphoenolpyruvate carboxykinase and nicotinic acid phosphoribosyltransferase for succinate production in engineered Escherichia coli.

    PubMed

    Jiang, Min; Chen, Xu; Liang, Liya; Liu, Rongming; Wan, Qing; Wu, Mingke; Zhang, Hanwen; Ma, Jiangfeng; Chen, Kequan; Ouyang, Pingkai

    2014-03-01

    Succinate is not the dominant fermentation product from xylose in wild-type Escherichia coli K12. E. coli BA 203 is a lactate dehydrogenase (ldhA), pyruvate formate lyase (pflB), and phosphoenolpyruvate (PEP)-carboxylase (ppc) deletion strain. To increase succinate accumulation and reduce byproduct formation, engineered E. coli BA204, in which ATP-forming PEP-carboxykinase (PEPCK) is overexpressed in BA203, was constructed and produced 2.17-fold higher succinate yield. To further improve the biomass and the consumption rate of xylose, nicotinic acid phosphoribosyltransferase (NAPRTase), a rate limiting enzyme in the synthesis of NAD(H), was also overexpressed. Thus, co-expression of PEPCK and NAPRTase in recombinant E. coli BA209 was investigated. In BA209, the pck gene and the pncB gene each have a trc promoter, hence, both genes are well expressed. During a 72-h anaerobic fermentation in sealed bottles, the total concentration of NAD(H) in BA209 was 1.25-fold higher than that in BA204, and the NADH/NAD+ ratio decreased from 0.28 to 0.11. During the exclusively anaerobic fermentation in a 3-L bioreactor, BA209 consumed 17.1 g L⁻¹ xylose and produced 15.5 g L⁻¹ succinate. Furthermore, anaerobic fermentation of corn stalk hydrolysate contained 30.1 g L⁻¹ xylose, 2.1 g L⁻¹ glucose and 1.5 g L⁻¹ arabinose, it produced a final succinate concentration of 17.2 g L⁻¹ with a yield of 0.94 g g⁻¹ total sugars. PMID:24564896

  2. Thermochemical characteristics of cellulose acetates with different degrees of acetylation

    NASA Astrophysics Data System (ADS)

    Larina, V. N.; Ur'yash, V. F.; Kushch, D. S.

    2012-12-01

    The standard enthalpies of combustion and formation of cellulose acetates with different degrees of acetylation are determined. It is established that there is a proportional dependence of these thermochemical characteristics vs. the degree of acetylation, weight fraction of bonded acetic acid, and molar mass of the repeating unit of cellulose acetates.

  3. Acetate concentrations and oxidation in salt marsh sediments

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Acetate concentrations and rates of acetate oxidation and sulfate reduction were measured in S. alterniflora sediments in New Hampshire and Massachusetts. Pore water extracted from cores by squeezing or centrifugation contained in greater than 0.1 mM acetate and, in some instances, greater than 1.0 mM. Pore water sampled nondestructively contained much less acetate, often less than 0.01 mM. Acetate was associated with roots, and concentrations varied with changes in plant physiology. Acetate turnover was very low whether whole core or slurry incubations were used. Radiotracers injected directly into soils yielded rates of sulfate reduction and acetate oxidation not significantly different from core incubation techniques. Regardless of incubation method, acetate oxidation did not account for a substantial percentage of sulfate reduction. These results differ markedly from data for unvegetated coastal sediments where acetate levels are low, oxidation rate constants are high, and acetate oxication rates greatly exceed rates of sulfate reduction. The discrepancy between rates of acetate oxidation and sulfate reduction in these marsh soils may be due either to the utilization of substrates other than acetate by sulfate reducers or artifacts associated with measurements of organic utilization by rhizosphere bacteria. Care must be taken when interpreting data from salt marsh sediments since the release of material from roots during coring may affect the concentrations of certain compounds as well as influencing results obtained when sediment incubations are employed.

  4. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100 gallons... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ethyl alcohol containing ethyl acetate....

  5. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100 gallons... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ethyl alcohol containing ethyl acetate....

  6. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100 gallons... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ethyl alcohol containing ethyl acetate....

  7. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100 gallons... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ethyl alcohol containing ethyl acetate....

  8. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100 gallons... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ethyl alcohol containing ethyl acetate....

  9. Kinetics of Ethyl Acetate Synthesis Catalyzed by Acidic Resins

    ERIC Educational Resources Information Center

    Antunes, Bruno M.; Cardoso, Simao P.; Silva, Carlos M.; Portugal, Ines

    2011-01-01

    A low-cost experiment to carry out the second-order reversible reaction of acetic acid esterification with ethanol to produce ethyl acetate is presented to illustrate concepts of kinetics and reactor modeling. The reaction is performed in a batch reactor, and the acetic acid concentration is measured by acid-base titration versus time. The…

  10. 21 CFR 582.5933 - Vitamin A acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Vitamin A acetate. 582.5933 Section 582.5933 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5933 Vitamin A acetate. (a) Product. Vitamin A acetate. (b) Conditions of use....

  11. 21 CFR 582.5933 - Vitamin A acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Vitamin A acetate. 582.5933 Section 582.5933 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5933 Vitamin A acetate. (a) Product. Vitamin A acetate. (b) Conditions of use....

  12. 21 CFR 582.5933 - Vitamin A acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Vitamin A acetate. 582.5933 Section 582.5933 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5933 Vitamin A acetate. (a) Product. Vitamin A acetate. (b) Conditions of use....

  13. 21 CFR 582.5933 - Vitamin A acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Vitamin A acetate. 582.5933 Section 582.5933 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5933 Vitamin A acetate. (a) Product. Vitamin A acetate. (b) Conditions of use....

  14. 21 CFR 582.5933 - Vitamin A acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Vitamin A acetate. 582.5933 Section 582.5933 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5933 Vitamin A acetate. (a) Product. Vitamin A acetate. (b) Conditions of use....

  15. Succinic acid production on xylose-enriched biorefinery streams by Actinobacillus succinogenes in batch fermentation

    DOE PAGESBeta

    Salvachua, Davinia; Mohagheghi, Ali; Smith, Holly; Bradfield, Michael F. A.; Nicol, Willie; Black, Brenna A.; Biddy, Mary J.; Dowe, Nancy; Beckham, Gregg T.

    2016-02-02

    Co-production of chemicals from lignocellulosic biomass alongside fuels holds promise for improving the economic outlook of integrated biorefineries. In current biochemical conversion processes that use thermochemical pretreatment and enzymatic hydrolysis, fractionation of hemicellulose-derived and cellulose-derived sugar streams is possible using hydrothermal or dilute acid pretreatment (DAP), which then offers a route to parallel trains for fuel and chemical production from xylose- and glucose-enriched streams. Succinic acid (SA) is a co-product of particular interest in biorefineries because it could potentially displace petroleum-derived chemicals and polymer precursors for myriad applications. Furthermore, SA production from biomass-derived hydrolysates has not yet been fully exploredmore » or developed.« less

  16. Hemolytic uremic syndrome and rhabdomyolysis in a patient with succinate coenzyme Q reductase (complex II) deficiency.

    PubMed

    Micheletti, M V; Lavoratti, G; Gasperini, S; Donati, M A; Pela, I

    2011-07-01

    Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Besides diarrhea-associated HUS, due to verotoxin-producing Escherichia coli, in children HUS without prodromal diarrhea may be associated with other infectious and autoimmune diseases, genetic defects of the complement-regulator alternative-pathway, and inborn errors of vitamin B12 metabolism. Rhabdomyolysis is the dissolution of skeletal muscle due to various causes, including inborn errors of metabolism. Recurrent rhabdomyolysis and HUS have been previously described in one patient with a genetic defect of oxidative phosphorylation. We report the case of a 2-year-old boy with recurrent HUS and rhabdomyolysis in whom a succinate coenzyme Q reductase (complex II) deficiency was diagnosed. We hypothesize that defects of oxidative phosphorylation could be another etiological factor in atypical HUS. PMID:21722608

  17. Gadolinium(III)-hydroxy ladders trapped in succinate frameworks with optimized magnetocaloric effect.

    PubMed

    Chen, Yan-Cong; Guo, Fu-Sheng; Zheng, Yan-Zhen; Liu, Jun-Liang; Leng, Ji-Dong; Tarasenko, Róbert; Orendáč, Martin; Prokleška, Jan; Sechovský, Vladimír; Tong, Ming-Liang

    2013-09-27

    Two kinds of inorganic gadolinium(III)-hydroxy "ladders", [2×n] and [3×n], were successfully trapped in succinate (suc) coordination polymers, [Gd2(OH)2(suc)2(H2O)]n·2nH2O (1) and [Gd6(OH)8(suc)5(H2O)2 ]n·4n H2O (2), respectively. Such coordination polymers could be regarded as alternating inorganic-organic hybrid materials with relatively high density. Magnetic and heat capacity studies reveal a large cryogenic magnetocaloric effect (MCE) in both compounds, namely (ΔH=70 kG) 42.8 J kg(-1) K(-1) for complex 1 and 48.0 J kg(-1) K(-1) for complex 2. The effect of the high density is evident, which gives very large volumetric MCEs up to 120 and 144 mJ cm(-3) K(-1) for complexes 1 and 2, respectively. PMID:23959529

  18. Eye Findings on Vigabatrin and Taurine Treatment in Two Patients with Succinic Semialdehyde Dehydrogenase Deficiency.

    PubMed

    Horvath, Gabriella-Ana; Hukin, Juliette; Stockler-Ipsiroglu, Sylvia G; Aroichane, Maryam

    2016-08-01

    We describe for the first time two patients with succinic semialdehyde dehydrogenase (SSADH) deficiency, who were found to have abnormal electroretinogram (ERG) examinations at baseline, or 6 months after vigabatrin treatment was started. This was somewhat reversible with L-taurine treatment, or minimally progressive. The mechanism of injury to the retina may be induced by elevations of γ-aminobutyric acid causing peripheral photoreceptor and ganglion cell damage, and this can be exacerbated by the use of vigabatrin. The use of taurine supplementation in tandem with vigabatrin may allow reversal of retinopathy and mitigate or slow down further deterioration. Further prospective clinical trials are required to evaluate this further. We recommend starting L-taurine therapy together with vigabatrin if a trial of vigabatrin is commenced in a patient with SSADH deficiency. Close monitoring of visual fields or ERG is also recommended at baseline and during vigabatrin therapy. PMID:27104484

  19. Interconversion of mechanical and dielectrical relaxation measurements for dicyclohexylmethyl-2-methyl succinate.

    PubMed

    Díaz-Calleja, R; Garcia-Bernabé, A; Sanchis, M J; del Castillo, L F

    2005-11-01

    A comparison between results of dielectrical relaxation and dynamic mechanical spectroscopies is carried out for the alpha-relaxation of the ester dicyclohexyl methyl-2-methyl succinate (DCMMS). The results for the dielectric permittivity and the shear modulus measurements are presented according to the empirical Havriliak-Negami (HN) equation. By using the time-temperature principle a master curve in each case was obtained for several temperatures. The comparative analysis presented here is based on the assumption of a relationship between rotational and shear viscosities. The former one is associated to the dielectrical relaxation, whereas the latter is associated to mechanical relaxation. Both viscosities are not necessarily equal in general, and we assume that the difference between them is an important factor to appropriately compare the dielectrical and mechanical results. PMID:16383609

  20. Viscoelastic Properties of Poly[(butylene succinate)-co-adipate] Nanocomposites.

    PubMed

    Al-Thabaiti, Shaeel A; Ray, Suprakas Sinha; Basahell, Sulaiman Nassir; Mokhtar, Mohamed

    2015-03-01

    This article reports the viscoelastic properties of poly[(butylene succinate)-co-adipate] (PBSA) nanocomposites. The nanocomposites of PBSA with various loadings of organically modified clay were prepared by melt-mixing in a batch-mixer. The solid and melt-state viscoelastic properties of neat PBSA and various nanocomposites were studied in detail. The dynamic mechanical studies demonstrated an increase in the storage modulus of PBSA matrix with organoclay loading. Melt-state rheological properties were found to be modified with organoclay loading changing from liquid-like, to gel-like and then viscoelastic solid-like. Such changes in viscoelastic properties along with the improvements in thermomechanical properties are expected to open opportunities for the use of PBSA extending its applications from the classical field of packaging to new niches such as tissue-engineering. PMID:26413658

  1. Enhanced performance of biodegradable poly(butylene succinate)/graphene oxide nanocomposites via in situ polymerization.

    PubMed

    Wang, X W; Zhang, C-A; Wang, P L; Zhao, J; Zhang, W; Ji, J H; Hua, K; Zhou, J; Yang, X B; Li, X P

    2012-05-01

    Poly(butylene succinate) (PBS)/graphene oxide (GO) nanocomposites were facilely prepared via in situ polymerization. The properties of the nanocomposites were studied using FTIR, XRD, and (1)H NMR, and the state of dispersion of GO in the PBS matrix was examined by SEM. The crystallization and melting behavior of the PBS matrix in the presence of dispersed GO nanosheets have been studied by DSC and polarized optical microscopy. Through the mechnical testing machine and DMA, PBS/GO nanocomposites with 3% GO have shown a 43% increase in tensile strength and a 45% improvement in storage modulus. This high performance of the nanocomposites is mainly attributed to the high strength of graphene oxide combined with the strong interfacial interactions in the uniformly dispersed PBS/GO nanocomposites. PMID:22420718

  2. Rheological behavior of branch modified poly(butylene succinate) by butyl glycidyl ether

    NASA Astrophysics Data System (ADS)

    Qi, Zhiguo; Zhang, Yu; Xu, Jun; Guo, Baohua

    2016-03-01

    The Butyl Glycidyl Ether (bge) is selected as a branch mononers and correspondingly poly(butylene succinate) PBS-bge copolymers is synthesised by polymerization. In this study, the dynamic viscoelastic is employed to study the rheological properties of homogeneous PBS and PBS-bge copolymers. The results indicated that all copolymers showed high mole weight and well matched the reaction mole ratio. But the PBS-bge copolymers exhibited a higher shear thinning behaviors than homogeneous PBS. And all PBS-bge copolymers exhibited a higher complex viscosity at low frequency indicating network-like structures were formed at the low shear frequency. In addition, the tanδ is remarkable decreased with the introducing of bge, which reflects that the elasticity of polymer is significantly improved. As a result, the branched modification has improved the ductility and toughness of the material obviously, especially when the branched ratio is more than 5%.

  3. Multi walled carbon nanotube nanocomposites with biodegradable poly(butylene succinate) and their physical characteristics.

    PubMed

    Hong, M K; Ko, S W; Park, J H; Choi, H J; Kim, J H

    2011-06-01

    In order to examine the influence of multi walled carbon nanotube (MWNT) on physical properties of its biodegradable polymer nanocomposite, biodegradable poly(buthylene succinate) (PBS), which was synthesized from diols and dicarboxylic acids, and MWNT nanocomposites were prepared via a melt-mixing method using a co-rotating intermeshing twin screw extruder. Microstructure of the PBS/MWNT nanocomposites and MWNT were investigated via both scanning electron microscopy and transmission electron microscopy. Their rheological properties were also characterized via rotation and oscillation tests using a rotational rheometer with parallel-plate geometry. It was found that shear viscosity, storage modulus and loss modulus of the nanocomposites examined by a rotational rheometer increased with the MWNT content. Especially their sharp increase for MWNT content of ca. 2.0 wt% was observed, indicating its percolation threshold from the rheological viewpoint which was higher than its electrical percolation threshold (1.0 wt%). PMID:21770188

  4. Biodegradation and Mechanical Properties of Poly(lactic acid)/Poly(butylene succinate) Blends

    NASA Astrophysics Data System (ADS)

    Kobayashi, Satoshi; Sugimoto, Satomi

    Polymer blends were fabricated with poly(lactic acid) (PLA) with better mechanical properties and poly(butylene succinate) (PBSU) with better biodegradable properties to clarify the effect of the blending ratio on the biodegradable and mechanical properties of the blends. The specimens were heat treated to improve the reduction in stiffness due to blending. Hydrolysis and soil burial tests up to 16 weeks were conducted to investigate the biodegradation properties. Young's modulus increased with increasing contents of PLA, whereas tensile strength is lowest in the PLA/PBSU (50/50) polymer blend before biodegradation because of the immiscibility of PLA and PBSU. Young's modulus kept constant up 16 weeks both in the hydrolysis and the soil burial tests. On the other hand, tensile strength decreased remarkably in the hydrolysis tests. The observation results of the specimen surface and the fracture surface indicate that the surface and bulk degradation occur in hydrolysis and soil burial tests, respectively

  5. Starch grafted poly(butylene succinate) via conjugating reaction and its role on enhancing the compatibility.

    PubMed

    Kanitporn, Suchao-in; Koombhongse, Piyawit; Chirachanchai, Suwabun

    2014-02-15

    A single step process of grafting poly(butylene succinate) (PBS) on starch to obtain starch-g-PBS in a heterogeneous system is proposed. Starch-g-PBS is accomplished by a conjugating reaction in chloroform at room temperature between hydroxyl groups of starch and carboxylic acid terminal groups of PBS by using N-N'-dicyclohexylcarbodiimide (DCC) conjugating agent. The grafting of PBS at both primary alcohol and secondary alcohol of starch is as high as 20-30% as confirmed by (1)H NMR and HMBC 2D NMR. The grafting of PBS results in a drastic changes of the crystallization as seen from the decrease in size of spherulite. The starch-g-PBS is a good compatibilizer between PBS and starch by promoting strong interfacial adhesion of the blend as evidenced from the improvement of modulus (2 times increase) and the miscibility of the blend in SEM images. PMID:24507260

  6. Synthesis of a γ-lactam library via formal cycloaddition of imines and substituted succinic anhydrides.

    PubMed

    Tan, Darlene Q; Atherton, Amy L; Smith, Austin J; Soldi, Cristian; Hurley, Katherine A; Fettinger, James C; Shaw, Jared T

    2012-03-12

    Formal cycloaddition reactions between imines and cyclic anhydrides serve as starting point for the synthesis of diverse libraries of small molecules. The synthesis of succinic anhydrides substituted with electron-withdrawing groups is facilitated by new mild conditions for alkylation of aryl-substituted acetyl esters with ethyl bromoacetate. These anhydrides are then used in formal cycloaddition reactions with imines to produce γ-lactams. 2-Fluoro-5-nitrophenylsuccinic anhydride reacts efficiently with imines to provide lactams that are further diversified by conversion of the nitro group to either an aniline and an azide for subsequent reactions with acylating agents and alkynes, respectively. The synthesis of cyanosuccinic anhydride is reported for the first time, and the use of this compound in reactions with imines and subsequent functionalization of the resultant lactams is demonstrated. PMID:22225535

  7. Poly(butylene succinate-co-butylene adipate)/cellulose nanocrystal composites modified with phthalic anhydride.

    PubMed

    Zhang, Xuzhen; Zhang, Yong

    2015-12-10

    As a kind of biomass nanofiller for polymers, cellulose nanocrystal (CNC) has good mechanical properties and reinforcing capability. To improve the compatibility of poly(butylene succinate-co-butylene adipate) (PBSA)/CNC composites, phthalic anhydride was used as a compatilizer during melt mixing, leading to the significant improvement of the mechanical properties and thermal stability of the composites, which is related to the better dispersion of CNC in the composites. The addition of phthalic anhydride could accelerate the crystallization of PBSA component as evidenced by the curves of isothermal crystallization of the composites, but had little effect on the crystalline polymorphs of PBSA component. The addition of phthalic anhydride could strongly improve the hydrophobicity of the composites. The good mechanical properties, fast crystallization and improved hydrophobicity of PBSA/CNC composites with phthalic anhydride are favor to their practical commercial utilization. PMID:26428099

  8. Succinic acid production from duckweed (Landoltia punctata) hydrolysate by batch fermentation of Actinobacillus succinogenes GXAS137.

    PubMed

    Shen, Naikun; Wang, Qingyan; Zhu, Jing; Qin, Yan; Liao, Siming; Li, Yi; Zhu, Qixia; Jin, Yanling; Du, Liqin; Huang, Ribo

    2016-07-01

    Duckweed is potentially an ideal succinic acid (SA) feedstock due to its high proportion of starch and low lignin content. Pretreatment methods, substrate content and nitrogen source were investigated to enhance the bioconversion of duckweed to SA and to reduce the costs of production. Results showed that acid hydrolysis was an effective pretreatment method because of its high SA yield. The optimum substrate concentration was 140g/L. The optimum substrate concentration was 140g/L. Corn steep liquor powder could be considered a feasible and inexpensive alternative to yeast extract as a nitrogen source. Approximately 57.85g/L of SA was produced when batch fermentation was conducted in a 1.3L stirred bioreactor. Therefore, inexpensive duckweed can be a promising feedstock for the economical and efficient production of SA through fermentation by Actinobacillus succinogenes GXAS137. PMID:27023386

  9. Continuous Succinic Acid Production by Actinobacillus succinogenes on Xylose-Enriched Hydrolysate

    DOE PAGESBeta

    Bradfield, Michael F. A.; Mohagheghi, Ali; Salvachua, Davinia; Smith, Holly; Black, Brenna A.; Dowe, Nancy; Beckham, Gregg T.; Nicol, Willie

    2015-11-14

    Bio-manufacturing of high-value chemicals in parallel to renewable biofuels has the potential to dramatically improve the overall economic landscape of integrated lignocellulosic biorefineries. However, this will require the generation of carbohydrate streams from lignocellulose in a form suitable for efficient microbial conversion and downstream processing appropriate to the desired end use, making overall process development, along with selection of appropriate target molecules, crucial to the integrated biorefinery. Succinic acid (SA), a high-value target molecule, can be biologically produced from sugars and has the potential to serve as a platform chemical for various chemical and polymer applications. However, the feasibility ofmore » microbial SA production at industrially relevant productivities and yields from lignocellulosic biorefinery streams has not yet been reported.« less

  10. Continuous Succinic Acid Production by Actinobacillus succinogenes on Xylose-Enriched Hydrolysate

    SciTech Connect

    Bradfield, Michael F. A.; Mohagheghi, Ali; Salvachua, Davinia; Smith, Holly; Black, Brenna A.; Dowe, Nancy; Beckham, Gregg T.; Nicol, Willie

    2015-11-14

    Bio-manufacturing of high-value chemicals in parallel to renewable biofuels has the potential to dramatically improve the overall economic landscape of integrated lignocellulosic biorefineries. However, this will require the generation of carbohydrate streams from lignocellulose in a form suitable for efficient microbial conversion and downstream processing appropriate to the desired end use, making overall process development, along with selection of appropriate target molecules, crucial to the integrated biorefinery. Succinic acid (SA), a high-value target molecule, can be biologically produced from sugars and has the potential to serve as a platform chemical for various chemical and polymer applications. However, the feasibility of microbial SA production at industrially relevant productivities and yields from lignocellulosic biorefinery streams has not yet been reported.

  11. Preparation and Characterization of Octenyl Succinic Anhydride Modified Taro Starch Nanoparticles.

    PubMed

    Jiang, Suisui; Dai, Lei; Qin, Yang; Xiong, Liu; Sun, Qingjie

    2016-01-01

    The polar surface and hydrophilicity of starch nanoparticles (SNPs) result in their poor dispersibility in nonpolar solvent and poor compatibility with hydrophobic polymers, which limited the application in hydrophobic system. To improve their hydrophobicity, SNPs prepared through self-assembly of short chain amylose debranched from cooked taro starch, were modified by octenyl succinic anhydride (OSA). Size via dynamic light scattering of OSA-SNPs increased compared with SNPs. Fourier transform infrared spectroscopy data indicated the OSA-SNPs had a new absorption peak at 1727 cm-1, which was the characteristic peak of carbonyl, indicating the formation of the ester bond. The dispersibility of the modified SNPs in the mixture of water with nonpolar solvent increased with increasing of degree of substitution (DS). OSA-SNPs appear to be a potential agent to stabilize the oil-water systems. PMID:26918568

  12. Radiation effects in polyisobutylene succinic anhydride modified with silica and magnetite nanoparticles

    NASA Astrophysics Data System (ADS)

    Zaharescu, T.; Borbath, I.; Vékás, L.

    2014-12-01

    Polyisobutylene succinic anhydride (PIBSA) was modified with nanoparticles of magnetite and silica for the appraising the modification in the thermal stability of organic component after gamma irradiation. Pristine anhydride was loaded with different amounts of nanofiller (1, 2 and 5 wt% of each oxide). Gamma exposure was performed in air at several doses: 10, 20, 50 and 100 kGy. The stability determinations were carried out by nonisothermal chemiluminescence in stationary air atmosphere. The presence of these oxides induces an increase in the oxidation level corresponding to their chemical availability as the filler amounts and exposure doses are enhanced. The oxidation takes essentially place on quaternary carbon atoms and double bonds, which was demonstrated by the presence of two chemiluminescence intensity peaks. The comparative analysis on the radiation oxidation of PIBSA modified with Fe3O4 and SiO2 is presented.

  13. Conformational steering in dicarboxy acids: the native structure of succinic acid.

    PubMed

    Jahn, Michaela K; Méndez, Estibaliz; Rajappan Nair, K P; Godfrey, Peter D; McNaughton, Don; Écija, Patricia; Basterretxea, Francisco J; Cocinero, Emilio J; Grabow, Jens-Uwe

    2015-08-14

    Succinic acid, a dicarboxylic acid molecule, has been investigated spectroscopically with computational support to elucidate the complex aspects of its conformational composition. Due to the torsional freedom of the carbon backbone and hydroxy groups, a large number of potentially plausible conformers can be generated with an indication that the gauche conformer is favored over the trans form. The microwave and millimeter wave spectra have been analyzed and accurate spectroscopic constants have been derived that correlate best with those of the lowest energy gauche conformer. For an unambiguous conformational identification measurements were extended to the monosubstituted isotopologues, precisely determining the structural properties. Besides bond distances and angles, particularly the dihedral angle has been determined to be 67.76(11)°, confirming the anomalous tendency of the methylene units to favor gauche conformers when a short aliphatic segment is placed between two carbonyl groups. PMID:25767836

  14. Release behaviors of porous poly(butylene succinate)/poly(epsilon-caprolactone) microcapsules containing indomethacin.

    PubMed

    Park, Soo-Jin; Lee, Yun-Mok; Hong, Sung-Kwon

    2006-02-01

    The biodegradable poly(butylene succinate)/poly(epsilon-caprolactone) (PBS/PCL) microcapsules containing indomethacin were prepared by emulsion solvent evaporation method. The morphologies, thermal properties, and release behaviors of PBS/PCL microcapsules were investigated. As a result, the microcapsules exhibited porous and spherical form in the presence of gelatin as a surfactant. From the DSC result, the PBS/PCL microcapsules showed the two exothermic peaks meaning the melting points of PCL and PBS. The results of FT-IR and DSC proved that the PBS and PCL were mixed so that the PBS/PCL microcapsules were composed of two wall-forming materials. And the release rate of indomethacin from the microcapsules was decreased with increasing the PCL content. It was noted that an addition of PCL on the PBS led to the decrease of pore size in the PBS/PCL microcapsules. PMID:16413177

  15. Preparation and Characterization of Octenyl Succinic Anhydride Modified Taro Starch Nanoparticles

    PubMed Central

    Jiang, Suisui; Dai, Lei; Qin, Yang; Xiong, Liu; Sun, Qingjie

    2016-01-01

    The polar surface and hydrophilicity of starch nanoparticles (SNPs) result in their poor dispersibility in nonpolar solvent and poor compatibility with hydrophobic polymers, which limited the application in hydrophobic system. To improve their hydrophobicity, SNPs prepared through self-assembly of short chain amylose debranched from cooked taro starch, were modified by octenyl succinic anhydride (OSA). Size via dynamic light scattering of OSA-SNPs increased compared with SNPs. Fourier transform infrared spectroscopy data indicated the OSA-SNPs had a new absorption peak at 1727 cm-1, which was the characteristic peak of carbonyl, indicating the formation of the ester bond. The dispersibility of the modified SNPs in the mixture of water with nonpolar solvent increased with increasing of degree of substitution (DS). OSA-SNPs appear to be a potential agent to stabilize the oil-water systems. PMID:26918568

  16. Core-in-cup tablet design of metoprolol succinate and its evaluation for controlled release.

    PubMed

    Nagaraju, Ravouru; Meera, Durgumahanthi Sai; Kaza, Rajesh; Arvind, Vakati Venkata; Venkateswarlu, Vobalaboina

    2009-12-01

    The core-in-cup matrix tablets of Metoprolol succinate were prepared by wet granulation technique. Of all the investigated formulations, the optimized formulation of MS-09 followed zero-order kinetics of drug release. Trail on MS-09 was formulated using 7.5% hydrogenated castor-oil (HCO) and 4% of hydroxyl propyl methylcellulose (HPMC K15M) with an objective to achieve a linear release profile for 24 h. There is no initial burst release, with 16.17% of drug released during the first hour and release was extended up to 24 hrs. Study of drug release kinetics was performed by application of dissolution data to various kinetic equations like zero-order; first order, Higuchi and Korsmeyer-Peppas, from R(2) value (0.9975) it was concluded that the drug release followed zero order kinetics with both erosion and diffusion as the release mechanisms. PMID:20025598

  17. Ionic liquids as novel solvents for biosynthesis of octenyl succinic anhydride-modified waxy maize starch.

    PubMed

    Li, Dandan; Zhang, Xiwen; Tian, Yaoqi

    2016-05-01

    Biosynthesis of octenyl succinic anhydride (OSA) starch was investigated using ionic liquids (ILs) as reaction media. Waxy maize starch was pretreated in 1-butyl-3-methylimidazolium chlorine and then esterified with OSA in 1-octyl-3-methylimidazolium nitrate by using Novozyme 435 as catalyst. The degree of substitution of OSA starch reached 0.0130 with 5 wt% starch concentration and 1 wt% lipase dosage based on ILs weight at 50 °C for 3h. The formation of OSA starch was confirmed by fourier transform infrared spectroscopy. Scanning electron microscopy and X-ray diffraction revealed that the morphology and crystal structure of starch were significantly destroyed. Thermogravimetric analysis showed that esterification decreased the thermal stability of starch. The successful lipase-catalyzed synthesis of OSA starch in ILs suggests that ILs are potential replacement of traditional organic solvents for starch ester biosynthesis. PMID:26797225

  18. Discovery of Potent Succinate-Ubiquinone Oxidoreductase Inhibitors via Pharmacophore-linked Fragment Virtual Screening Approach.

    PubMed

    Xiong, Li; Zhu, Xiao-Lei; Gao, Hua-Wei; Fu, Yu; Hu, Sheng-Quan; Jiang, Li-Na; Yang, Wen-Chao; Yang, Guang-Fu

    2016-06-22

    Succinate-ubiquinone oxidoreductase (SQR) is an attractive target for fungicide discovery. Herein, we report the discovery of novel SQR inhibitors using a pharmacophore-linked fragment virtual screening approach, a new drug design method developed in our laboratory. Among newly designed compounds, compound 9s was identified as the most potent inhibitor with a Ki value of 34 nM against porcine SQR, displaying approximately 10-fold higher potency than that of the commercial control penthiopyrad. Further inhibitory kinetics studies revealed that compound 9s is a noncompetitive inhibitor with respect to the substrate cytochrome c and DCIP. Interestingly, compounds 8a, 9h, 9j, and 9k exhibited good in vivo preventive effects against Rhizoctonia solani. The results obtained from molecular modeling showed that the orientation of the R(2) group had a significant effect on binding with the protein. PMID:27225833

  19. Polybutylene succinate adipate/starch blends: a morphological study for the design of controlled release films.

    PubMed

    Khalil, Fadi; Galland, Sophie; Cottaz, Amandine; Joly, Catherine; Degraeve, Pascal

    2014-08-01

    Films made of plasticized starch (PLS)/poly(butylene succinate co-butylene adipate) (PBSA) blends were prepared by thermomechanical processing varying the PBSA proportions in blends to obtain biphasic materials with distinct morphologies. These morphologies were characterized by selective extraction of each phase, microscopic observations, and selective water/oxygen permeation properties. These experiments allowed identifying the blend compositions corresponding to the beginning of partial continuity (cluster partial percolation) until total continuity of each phases. This property was related to the controlled release of model molecule (fluorescein) previously dispersed in the PLS and revealed that its release depended on the tortuosity of the PLS phase tailored by the polymer blends composition and by the limited swelling of the PLS when entrapped in the PBSA phase. Future applications will focus on food preservatives dispersed in PBSA-PLS blends to obtain active antimicrobial packaging put in direct contact with intermediate to high moisture foods. PMID:24751274

  20. Co-fermentation of acetate and sugars facilitating microbial lipid production on acetate-rich biomass hydrolysates.

    PubMed

    Gong, Zhiwei; Zhou, Wenting; Shen, Hongwei; Yang, Zhonghua; Wang, Guanghui; Zuo, Zhenyu; Hou, Yali; Zhao, Zongbao K

    2016-05-01

    The process of lignocellulosic biomass routinely produces a stream that contains sugars plus various amounts of acetic acid. As acetate is known to inhibit the culture of microorganisms including oleaginous yeasts, little attention has been paid to explore lipid production on mixtures of acetate and sugars. Here we demonstrated that the yeast Cryptococcus curvatus can effectively co-ferment acetate and sugars for lipid production. When mixtures of acetate and glucose were applied, C. curvatus consumed both substrates simultaneously. Similar phenomena were also observed for acetate and xylose mixtures, as well as acetate-rich corn stover hydrolysates. More interestingly, the replacement of sugar with equal amount of acetate as carbon source afforded higher lipid titre and lipid content. The lipid products had fatty acid compositional profiles similar to those of cocoa butter, suggesting their potential for high value-added fats and biodiesel production. This co-fermentation strategy should facilitate lipid production technology from lignocelluloses. PMID:26874438

  1. Multiple-anion nonvolatile acetal (MANA) resists

    NASA Astrophysics Data System (ADS)

    Guevremont, Jeffrey M.; Brainard, Robert L.; Reeves, Scott D.; Zhou, Xin; Nguyen, Thinh B.; Mackevich, Joseph F.; Anderson, Erik H.; Taylor, Gary N.

    2001-08-01

    New acetal or ketal blocking reagents were investigated for use in e-beam lithography and compared with the performance of ethyl vinyl either (EVE). Three blocking groups, (alpha) -Angelicalactone (AL), 6-methylene-5,6-benzo-1,4- dioxane (MBD), and MANA50 (an undisclosed blocking group used to show the potential of this chemistry) were reacted with poly(p-hydroxystyrene) (PHS) under acid catalyzed conditions to form AL-PHS, MBD-PHS, MANA50-PHS. The performance objectives pursued in the design of these new materials was to use acetal (ketal) chemistry to deliver wide process latitudes (e.g. good PED performance and minimal PEB sensitivity), use high molecular weight blocking groups to eliminate outgassing, and use the novel concept of multiple anions to deliver lithographic performance. These new materials are called Multiple Anion Nonvolatile Acetal (MANA) resists. Resists films were exposed with 50kV electrons, post exposure baked (PEB), and developed with 0.26 N TMAH. Resists prepared with the third blocking group, MANA50, gave contrast and imaging performance independent of PEB humidity and were relatively insensitive to PEB temperature and post exposure delay (PED). These resists gave the best resolution (90 nm) and profiles of all the materials tested, as well as showing no outgassing (as measured by film thickness loss).

  2. Poly(ω-pentadecalactone-co-butylene-co-succinate) Nanoparticles as Biodegradable Carriers for Camptothecin Delivery

    PubMed Central

    Liu, Jie; Jiang, Zhaozhong; Zhang, Shengmin; Saltzman, W. Mark

    2009-01-01

    In this study, we show that degradable particles of a hydrophobic polymer can effectively deliver drugs to tumors after i.v. administration. Free-standing nanoparticles with diameters of 100–300 nm were successfully fabricated from highly hydrophobic, biodegradable poly(ω-pentadecalactone- co-butylene-co-succinate) (PPBS) copolyesters. PPBS copolymers with various compositions (20–80 mol% PDL unit contents) were synthesized via copolymerization of ω-pentadecalactone (PDL), diethyl succinate (DES), and 1,4-butanediol (BD) using Candida antarctica lipase B (CALB) as the catalyst. Camptothecin (CPT, 12–22%) was loaded into PPBS nanoparticles with high encapsulation efficiency (up to 96%) using a modified oil-in-water single emulsion technique. The CPT-loaded nanoparticles had a zeta potential of about −10 mV. PPBS particles were non toxic in cell culture. Upon encapsulation, the active lactone form of CPT was remarkably stabilized and no lactone-to-carboxylate structural conversion was observed for CPT-loaded PPBS nanoparticles incubated in both phosphate-buffered saline (PBS, pH = 7.4) and DMEM medium for at least 24 hr. In PBS at 37 °C, CPT-loaded PPBS nanoparticles showed a low burst CPT release (20–30%) within the first 24 hrs followed by a sustained, essentially complete, release of the remaining drug over the subsequent 40 days. Compared to free CPT, CPT-loaded PPBS nanoparticles showed a significant enhancement of cellular uptake, higher cytotoxicity against Lewis lung carcinoma and 9L cell lines in vitro, a longer circulation time, and substantially better antitumor efficacy in vivo. These results demonstrate the potential of PPBS nanoparticles as long-term stable and effective drug delivery systems in cancer therapy. PMID:19632718

  3. Poly(omega-pentadecalactone-co-butylene-co-succinate) nanoparticles as biodegradable carriers for camptothecin delivery.

    PubMed

    Liu, Jie; Jiang, Zhaozhong; Zhang, Shengmin; Saltzman, W Mark

    2009-10-01

    In this study, we show that degradable particles of a hydrophobic polymer can effectively deliver drugs to tumors after i.v. administration. Free-standing nanoparticles with diameters of 100-300 nm were successfully fabricated from highly hydrophobic, biodegradable poly(omega-pentadecalactone-co-butylene-co-succinate) (PPBS) copolyesters. PPBS copolymers with various compositions (20-80 mol% PDL unit contents) were synthesized via copolymerization of omega-pentadecalactone (PDL), diethyl succinate (DES), and 1,4-butanediol (BD) using Candida antarctica lipase B (CALB) as the catalyst. Camptothecin (CPT, 12-22%) was loaded into PPBS nanoparticles with high encapsulation efficiency (up to 96%) using a modified oil-in-water single emulsion technique. The CPT-loaded nanoparticles had a zeta potential of about -10 mV. PPBS particles were non-toxic in cell culture. Upon encapsulation, the active lactone form of CPT was remarkably stabilized and no lactone-to-carboxylate structural conversion was observed for CPT-loaded PPBS nanoparticles incubated in both phosphate-buffered saline (PBS, pH=7.4) and DMEM medium for at least 24 h. In PBS at 37 degrees C, CPT-loaded PPBS nanoparticles showed a low burst CPT release (20-30%) within the first 24 h followed by a sustained, essentially complete, release of the remaining drug over the subsequent 40 days. Compared to free CPT, CPT-loaded PPBS nanoparticles showed a significant enhancement of cellular uptake, higher cytotoxicity against Lewis lung carcinoma and 9L cell lines in vitro, a longer circulation time, and substantially better antitumor efficacy in vivo. These results demonstrate the potential of PPBS nanoparticles as long-term stable and effective drug delivery systems in cancer therapy. PMID:19632718

  4. Involvement of the carboxyl group in QPs in interaction with succinate dehydrogenase

    SciTech Connect

    Xu, J.; Yu, L.; Yu, C.

    1987-05-01

    Bovine heart mitochondrial succinate-ubiquinone reductase (SQR) can be resolved into two reconstitutively active fractions; soluble succinate dehydrogenase (SDH), and a two-subunit Q-binding protein known as QPs or cytochrome b/sub 560/ fraction. The interaction between SDH and QPs involves both hydrophobic and ionic interactions. The involvement of an amino group in SDH has been established, the participation of a negatively charged group in QPs was then being speculated. Recently, they have used dicyclohexyl carbodiimide (DCCD) to study the involvement of carboxyl group in QPs with respect to interaction with SDH. When isolated QPs was treated with a 300-molar excess of DCCD per mole of protein at pH 6.0 in the presence of 0.2% D-N-gluco-N-methyl-decanamide, more than 80% of the reconstitutive activity of QPs was diminished. The inhibition of QPs by DCCD is pH and detergent concentration dependent. When intact or reconstituted SQR was treated with DCCD, no inhibition was observed, indicating that a carboxyl group in QPs which is essential for interaction with SDH is protected from DCCD modification in the presence of active SDH. No protecting effect was observed when reconstitutively inactive SDH was used, indicating that there is no interaction between reconstitutively inactive SDH and QPs. The (/sup 14/C)-DCCD labeling study showed that the DCCD was incorporated into the smaller subunit of QPs. The modification of QPs by DCCD also caused an alteration of spectral characteristics of cytochrome b/sub 560/.

  5. Targeting succinate:ubiquinone reductase potentiates the efficacy of anticancer therapy.

    PubMed

    Kruspig, Björn; Valter, Kadri; Skender, Belma; Zhivotovsky, Boris; Gogvadze, Vladimir

    2016-08-01

    Mitochondria play a pivotal role in apoptosis: permeabilization of the outer mitochondrial membrane and the release of pro-apoptotic proteins from the intermembrane space of mitochondria are regarded as the key event in apoptosis induction. Here we demonstrate how non-toxic doses of the mitochondrial Complex II inhibitor thenoyltrifluoroacetone (TTFA), which specifically inhibits the ubiquinone-binding site of succinate dehydrogenase (SDH), synergistically stimulated cell death, induced by harmless doses of cisplatin in a panel of chemoresistant neuroblastoma cell lines. Apoptotic cell death was confirmed by cytochrome c release from the mitochondria, cleavage of poly ADP-ribose polymerase, processing of caspase-3, which is an important executive enzyme in apoptosis, and caspase-3-like activity. Methyl malonate, an inhibitor of the SDHA subunit partially reversed apoptosis stimulated by TTFA in SK-N-BE(2) neuroblastoma cells (NB), indicating that sensitization requires oxidation of succinate. In contrast, in IMR-32 NB cells, the same concentrations of TTFA markedly suppressed cisplatin-induced apoptosis. Comparison of oxygen consumption in cisplatin-resistant SK-N-BE(2) and cisplatin-sensitive IMR-32 cells clearly demonstrated impaired Complex II activity in IMR-32 cells. We also found that in SK-N-BE(2) cells co-treatment with cisplatin and TTFA markedly stimulated formation of reactive oxygen species (ROS), whereas in IMR cells, cisplatin-mediated ROS production was attenuated by TTFA, which explains apoptosis suppression in these cells. Thus, functionally active SDH is a prerequisite for the ROS-mediated sensitization to treatment by TTFA. PMID:27140478

  6. Microbial degradation of an aliphatic polyester with a high melting point, poly(tetramethylene succinate).

    PubMed

    Pranamuda, H; Tokiwa, Y; Tanaka, H

    1995-05-01

    The biodegradability of poly(tetramethylene succinate) (PTMS), a synthetic aliphatic polyester with a high melting point, was evaluated. The ecological study showed that the distribution of PTMS-degrading microorganisms in soil environments was quite restricted compared with the distribution of microorganisms that degrade poly((epsilon)-caprolactone) (PCL), a polyester with a low melting point. However, in soil samples in which the formation of a clear zone was observed, PTMS-degrading microorganisms constituted 0.2 to 6.0% of the total number of microorganisms, which is very close to the percentage (0.8 to 8.0%) observed for PCL-degrading microorganisms. Five strains were isolated from colonies which formed distinct clear zones on agar plates with emulsified PTMS. In liquid cultures of the isolates with ground PTMS powder, strain HT-6, an actinomycete, showed the highest PTMS degrading activity. It assimilated about 60% of the ground PTMS powder after 8 days of cultivation. When a PTMS emulsion was used, a higher degradation rate was observed and more than 90% of the PTMS was assimilated in 6 days. PTMS degradation products were analyzed by gas chromatography, and it was found that 1,4-butanediol, 4-hydroxy n-butyrate, and succinic acid accumulated during cultivation. Degradation of PTMS film by the strain occurred in two steps: fragmentation and then the formation of hemispherical holes on the surface of the film. Strain HT-6 was also able to assimilate PCL and poly((beta)-hydroxybutyrate) (PHB). The crude enzyme showed a wide range of substrate specificity, being able to degrade low-molecular-weight PTMS, PCL, PHB, and even high-molecular-weight PTMS. PMID:16535023

  7. Identification of succinic semialdehyde reductases from Geobacter: expression, purification, crystallization, preliminary functional, and crystallographic analysis

    SciTech Connect

    Zhang, Yanfeng; Gao, Xiaoli; Zheng, Yi; Garavito, R. Michael

    2012-04-30

    Succinic semialdehyde reductase (SSAR) is an important enzyme involved in {gamma}-aminobutyrate (GABA) metabolism. By converting succinic semialdehyde (SSA) to {gamma}-hydroxybutyrate (GHB), the SSAR facilitates an alternative pathway for GABA degradation. In this study, we identified SSARs from Geobacter sulfurreducens and Geobacter metallireducens (GsSSAR and GmSSAR, respectively). The enzymes were over-expressed in Escherichia coli and purified to near homogeneity. Both GsSSAR and GmSSAR showed the activity of reducing SSA using nicotinamide adenine dinucleotide phosphate as a co-factor. The oligomeric sizes of GsSSAR and GmSSAR, as determined by analytical size exclusion chromatography, suggest that the enzymes presumably exist as tetramers in solution. The recombinant GsSSAR and GmSSAR crystallized in the presence of NADP{sup +}, and the resulting crystals diffracted to 1.89 {angstrom} (GsSSAR) and 2.25 {angstrom} (GmSSAR) resolution. The GsSSAR and GmSSAR crystals belong to the space groups P2{sub 1}22{sub 1} (a = 99.61 {angstrom}, b = 147.49 {angstrom}, c = 182.47 {angstrom}) and P1 (a = 75.97 {angstrom}, b = 79.14 {angstrom}, c = 95.47 {angstrom}, {alpha} = 82.15{sup o}, {beta} = 88.80{sup o}, {gamma} = 87.66{sup o}), respectively. Preliminary crystallographic data analysis suggests the presence of eight protein monomers in the asymmetric units for both GsSSAR and GmSSAR.

  8. Methylprednisolone sodium succinate-associated macroglossia in a critically ill patient.

    PubMed

    Igneri, Lauren A; Czosnowski, Quinn A; Whitman, Craig B

    2013-02-01

    Allergic hypersensitivity reactions are a rare adverse effect of corticosteroids. Previous reports have identified patients who developed symptoms of urticaria, dyspnea, hypotension, bronchospasm, and angioedema occurring within minutes to an hour after corticosteroid administration. A 35-year-old woman is described who developed an atypical reaction of isolated macroglossia after receiving intravenous methylprednisolone sodium succinate for myasthenic crisis. Macroglossia was identified on day 2 of therapy and worsened through day 5. On day 5, she was transitioned to prednisone 50 mg daily administered by feeding tube. Tongue swelling improved by day 7 and on day 10, the patient was extubated. The patient required reintubation due to stridor, but received a tracheostomy and was weaned off mechanical ventilation by day 15. The reaction was not confirmed with skin-prick tests, intradermal tests, or a drug rechallenge; however, she had previously received and tolerated all other drugs administered during this time. Due to the timing of administration and onset of symptoms, we feel this adverse drug reaction was likely due to administration of methylprednisolone. Applying the Naranjo adverse drug reaction probability scale to this case, a score of six was obtained, indicating a probable association between the administration of methylprednisolone and the development of macroglossia. As intravenous corticosteroids are often used in the treatment of allergic reactions, they may be overlooked as a cause of macroglossia and other allergic reactions; therefore, practitioners need to be aware of the possibility of this adverse effect secondary to corticosteroid administration. In the event of methylprednisolone sodium succinate-induced macroglossia, alternative nonesterified corticosteroids, such as dexamethasone or prednisone, should be considered if continuation of therapy is required. PMID:23386601

  9. Nucleotide sequence encoding the flavoprotein and hydrophobic subunits of the succinate dehydrogenase of Escherichia coli.

    PubMed Central

    Wood, D; Darlison, M G; Wilde, R J; Guest, J R

    1984-01-01

    The nucleotide sequence of a 3614 base-pair segment of DNA containing the sdhA gene, encoding the flavoprotein subunit of succinate dehydrogenase of Escherichia coli, and two genes sdhC and sdhD, encoding small hydrophobic subunits, has been determined. Together with the iron-sulphur protein gene (sdhB) these genes form an operon (sdhCDAB) situated between the citrate synthase gene (gltA) and the 2-oxoglutarate dehydrogenase complex genes (sucAB): gltA-sdhCDAB-sucAB. Transcription of the gltA and sdhCDAB gene appears to diverge from a single intergenic region that contains two pairs of potential promoter sequences and two putative CRP (cyclic AMP receptor protein)-binding sites. The sdhA structural gene comprises 1761 base-pairs (587 codons, excluding the initiation codon, AUG) and it encodes a polypeptide of Mr 64268 that is strikingly homologous with the flavoprotein subunit of fumarate reductase (frdA gene product). The FAD-binding region, including the histidine residue at the FAD-attachment site, has been identified by its homology with other flavoproteins and with the flavopeptide of the bovine heart mitochondrial succinate dehydrogenase. Potential active-site cysteine and histidine residues have also been indicated by the comparisons. The sdhC (384 base-pairs) and sdhD (342 base-pairs) structural genes encode two strongly hydrophobic proteins of Mr 14167 and 12792 respectively. These proteins resemble in size and composition, but not sequence, the membrane anchor proteins of fumarate reductase (the frdC and frdD gene products). PMID:6383359

  10. Differences between the succinate dehydrogenase sequences of isopyrazam sensitive Zymoseptoria tritici and insensitive Fusarium graminearum strains.

    PubMed

    Dubos, Tiphaine; Pasquali, Matias; Pogoda, Friederike; Casanova, Angèle; Hoffmann, Lucien; Beyer, Marco

    2013-01-01

    Forty-one Zymoseptoria tritici strains isolated in Luxembourg between 2009 and 2010 were highly sensitive towards the new succinate dehydrogenase inhibitor (SDHI) isopyrazam, with concentrations inhibiting fungal growth by 50% (EC50) ranging from 0.0281 to 4.53μM, whereas 41 Fusarium graminearum strains isolated in Europe and Northern America between 1969 and 2009 were insensitive with the average rate of inhibition converging towards 28% with increasing isopyrazam concentration. Seven isolates of both species covering the range of isopyrazam sensitivities observed in the present study were selected for the sequencing of the subunits B, C and D of the succinate dehydrogenase (sdh) gene. Predicted sdh amino acid sequences of subunits B, C and D were identical among F. graminearum strains. By comparing with fungal strains where resistance towards SDHIs was previously reported, three variations were unique to F. graminearum; B-D130N located in the iron-sulfur cluster [2Fe-2S], B-A275T located in the [3Fe-4S] cluster and an additional S at amino acid position 83-84 of sdhC, probably modifying structurally the ubiquinone binding site and therefore the biological activity of the fungicide. No variation was found among the Z. tritici strains in subunits B and D. Two variations were observed within the subunit C sequences of Z. tritici strains: C-N33T and C-N34T. The difference in EC50 values between Z. tritici strains with the NN and TT configuration was non-significant at P=0.289. Two outliers in the Z. tritici group with significantly higher EC50 values that were not related to mutations in the sdhB, sdhC, or sdhD were detected. The role of isopyrazam for the control of F. graminearum and Z. tritici in Luxembourg is discussed. PMID:24238287

  11. Hygroscopic growth and droplet activation of soot particles: uncoated, succinic or sulfuric acid coated

    NASA Astrophysics Data System (ADS)

    Henning, S.; Ziese, M.; Kiselev, A.; Saathoff, H.; Möhler, O.; Mentel, T. F.; Buchholz, A.; Spindler, C.; Michaud, V.; Monier, M.; Sellegri, K.; Stratmann, F.

    2011-10-01

    The hygroscopic growth and droplet activation of uncoated soot particles and such coated with succinic acid and sulfuric acid were investigated during the IN-11 campaign at the Aerosol Interaction and Dynamics in the Atmosphere (AIDA) facility. A GFG-1000 soot generator applying nitrogen, respectively argon as carrier gas and a miniCAST soot generator were utilized to generate soot particles. Different organic carbon (OC) to black carbon (BC) ratios were adjusted for the CAST-soot by varying the fuel to air ratio. The hygroscopic growth was investigated by means of the mobile Leipzig Aerosol Cloud Interaction Simulator (LACIS-mobile) and two different Hygroscopicity Tandem Differential Mobility Analyzers (HTDMA, VHTDMA). Two Cloud Condensation Nucleus Counter (CCNC) were applied to measure the activation of the particles. For the untreated soot particles neither hygroscopic growth nor activation was observed, with exception of a partial activation of GFG-soot generated with argon as carrier gas. Coatings of succinic acid lead to a detectable hygroscopic growth of GFG-soot and enhanced the activated fraction of GFG- (carrier gas: argon) and CAST-soot, whereas no hygroscopic growth of the coated CAST-soot was found. Sulfuric acid coatings lead to an OC-content dependent hygroscopic growth of CAST-soot. Such a dependence was not observed for activation measurements. Coating with sulfuric acid decreased the amount of Polycyclic Aromatic Hydrocarbons (PAH), which were detected by AMS-measurements in the CAST-soot, and increased the amount of substances with lower molecular weight than the initial PAHs. We assume, that these reaction products increased the hygroscopicity of the coated particles in addition to the coating substance itself.

  12. Hygroscopic growth and droplet activation of soot particles: uncoated, succinic or sulfuric acid coated

    NASA Astrophysics Data System (ADS)

    Henning, S.; Ziese, M.; Kiselev, A.; Saathoff, H.; Möhler, O.; Mentel, T. F.; Buchholz, A.; Spindler, C.; Michaud, V.; Monier, M.; Sellegri, K.; Stratmann, F.

    2012-05-01

    The hygroscopic growth and droplet activation of uncoated soot particles and such coated with succinic acid and sulfuric acid were investigated during the IN-11 campaign at the Aerosol Interaction and Dynamics in the Atmosphere (AIDA) facility. A GFG-1000 soot generator applying either nitrogen or argon as carrier gas and a miniCAST soot generator were utilized to generate soot particles. Different organic carbon (OC) to black carbon (BC) ratios were adjusted for the CAST-soot by varying the fuel to air ratio. The hygroscopic growth was investigated by means of the mobile Leipzig Aerosol Cloud Interaction Simulator (LACIS-mobile) and two different Hygroscopicity Tandem Differential Mobility Analyzers (HTDMA, VHTDMA). Two Cloud Condensation Nucleus Counter (CCNC) were applied to measure the activation of the particles. For the untreated soot particles neither hygroscopic growth nor activation was observed at a supersaturation of 1%, with exception of a partial activation of GFG-soot generated with argon as carrier gas. Coatings of succinic acid lead to a detectable hygroscopic growth of GFG-soot and enhanced the activated fraction of GFG- (carrier gas: argon) and CAST-soot, whereas no hygroscopic growth of the coated CAST-soot was found. Sulfuric acid coatings led to an OC-content dependent hygroscopic growth of CAST-soot. Such a dependence was not observed for activation measurements. Coating with sulfuric acid decreased the amount of Polycyclic Aromatic Hydrocarbons (PAH), which were detected by AMS-measurements in the CAST-soot, and increased the amount of substances with lower molecular weight than the initial PAHs. We assume that these reaction products increased the hygroscopicity of the coated particles in addition to the coating substance itself.

  13. Excess NO Predisposes Mitochondrial Succinate-Cytochrome c Reductase to Produce Hydroxyl Radical†

    PubMed Central

    Chen, Jingfeng; Chen, Chwen-Lih; Alevriadou, B. Rita; Zweier, Jay L.; Chen, Yeong-Renn

    2011-01-01

    Mitochondria–derived oxygen free radical(s) are important mediators of oxidative cellular injury. It is widely hypothesized that excess NO enhances O2•− generated by mitochondria under certain pathological conditions. In the mitochondrial electron transport chain, succinate-cytochrome c reductase (SCR) catalyzes the electron transfer reaction from succinate to cytochrome c. To gain the insights into the molecular mechanism of how NO overproduction may mediate the oxygen free radical generation by SCR, we employed isolated SCR, cardiac myoblast H9c2, and endothelial cells to study the interaction of NO with SCR in vitro and ex vivo. Under the conditions of enzyme turnover in the presence of NO donor (DEANO), SCR gained pro-oxidant function for generating hydroxyl radical as detected by EPR spin trapping using DEPMPO. The EPR signal associated with DEPMPO/•OH adduct was nearly completely abolished in the presence of catalase or an iron chelator and partially inhibited by SOD, suggesting the involvement of the iron-H2O2 dependent Fenton reaction or O2•−–dependent Haber-Weiss mechanism. Direct EPR measurement of SCR at 77 °K indicated the formation of a nonheme iron-NO complex, implying that electron leakage to molecular oxygen was enhanced at the FAD cofactor, and that excess NO predisposed SCR to produce •OH. In H9c2 cells, SCR dependent oxygen free radical generation was stimulated by NO released from DEANO or produced by the cells following exposure to hypoxia/reoxygenation. With shear exposure that led to overproduction of NO by the endothelium, SCR mediated oxygen free radical production was also detected in cultured vascular endothelial cells. PMID:21406178

  14. Overview on mechanisms of acetic acid resistance in acetic acid bacteria.

    PubMed

    Wang, Bin; Shao, Yanchun; Chen, Fusheng

    2015-02-01

    Acetic acid bacteria (AAB) are a group of gram-negative or gram-variable bacteria which possess an obligate aerobic property with oxygen as the terminal electron acceptor, meanwhile transform ethanol and sugar to corresponding aldehydes, ketones and organic acids. Since the first genus Acetobacter of AAB was established in 1898, 16 AAB genera have been recorded so far. As the main producer of a world-wide condiment, vinegar, AAB have evolved an elegant adaptive system that enables them to survive and produce a high concentration of acetic acid. Some researches and reviews focused on mechanisms of acid resistance in enteric bacteria and made the mechanisms thoroughly understood, while a few investigations did in AAB. As the related technologies with proteome, transcriptome and genome were rapidly developed and applied to AAB research, some plausible mechanisms conferring acetic acid resistance in some AAB strains have been published. In this review, the related mechanisms of AAB against acetic acid with acetic acid assimilation, transportation systems, cell morphology and membrane compositions, adaptation response, and fermentation conditions will be described. Finally, a framework for future research for anti-acid AAB will be provided. PMID:25575804

  15. [Degradation of oxytetracycline with ozonation in acetic acid solvent].

    PubMed

    Li, Shi-Yin; Li, Xiao-Rong; Zhu, Yi-Ping; Zhu, Jiang-Peng; Wang, Guo-Xiang

    2012-12-01

    Use acetic acid as the media of ozone degradation of oxytetracycline (OTC), and effects of the initial dosing ratio of ozone/OTC, ozone flow, free radical scavenger, metal ions on the removal rate of OTC were investigated respectively. The results showed that acetic acid had a high ozone stability and solubility. OTC had a high removal rate and degradation rate in acetic acid solution. With the increase of OTC dosage, the removal rate of OTC decreased in acetic acid. Removal rate of OTC was increased distinctly when ozone flow increased properly. It was also observed that free radical scavenger had a significantly negative effect on OTC ozonation degradation in acetic acid. Furthermore the main reactions of OTC ozone oxidation were direct oxidation and indirect oxidation in acetic acid. When Fe3+ and Co2+ were existent in acetic acid, the degradation of OTC was inhibited significantly. PMID:23379161

  16. Acetic acid removal from corn stover hydrolysate using ethyl acetate and the impact on Saccharomyces cerevisiae bioethanol fermentation.

    PubMed

    Aghazadeh, Mahdieh; Ladisch, Michael R; Engelberth, Abigail S

    2016-07-01

    Acetic acid is introduced into cellulose conversion processes as a consequence of composition of lignocellulose feedstocks, causing significant inhibition of adapted, genetically modified and wild-type S. cerevisiae in bioethanol fermentation. While adaptation or modification of yeast may reduce inhibition, the most effective approach is to remove the acetic acid prior to fermentation. This work addresses liquid-liquid extraction of acetic acid from biomass hydrolysate through a pathway that mitigates acetic acid inhibition while avoiding the negative effects of the extractant, which itself may exhibit inhibition. Candidate solvents were selected using simulation results from Aspen Plus™, based on their ability to extract acetic acid which was confirmed by experimentation. All solvents showed varying degrees of toxicity toward yeast, but the relative volatility of ethyl acetate enabled its use as simple vacuum evaporation could reduce small concentrations of aqueous ethyl acetate to minimally inhibitory levels. The toxicity threshold of ethyl acetate, in the presence of acetic acid, was found to be 10 g L(-1) . The fermentation was enhanced by extracting 90% of the acetic acid using ethyl acetate, followed by vacuum evaporation to remove 88% removal of residual ethyl acetate along with 10% of the broth. NRRL Y-1546 yeast was used to demonstrate a 13% increase in concentration, 14% in ethanol specific production rate, and 11% ethanol yield. This study demonstrated that extraction of acetic acid with ethyl acetate followed by evaporative removal of ethyl acetate from the raffinate phase has potential to significantly enhance ethanol fermentation in a corn stover bioethanol facility. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:929-937, 2016. PMID:27090191

  17. Temperature dependence of ion transport in dilute tetrabutylammonium triflate-acetate solutions and self-diffusion in pure acetate liquids.

    PubMed

    Bopege, Dharshani N; Petrowsky, Matt; Fleshman, Allison M; Frech, Roger; Johnson, Matthew B

    2012-01-12

    Conductivities and static dielectric constants for 0.0055 M tetrabutylammonium trifluoromethanesulfonate in n-butyl acetate, n-pentyl acetate, n-hexyl acetate, n-octyl acetate, and n-decyl acetate have been collected over the temperature range of 0-80 °C. Self-diffusion coefficients and static dielectric constants of pure acetates were obtained over the same temperature range. Both temperature-dependent diffusion coefficients and ionic conductivities of these pure acetates and dilute acetate solutions can be accurately described by the compensated Arrhenius formalism. Activation energies were calculated from compensated Arrhenius plots for both conductivity and diffusion data. Activation energies are higher for conductivity data of 0.0055 M TbaTf-acetates compared to diffusion data of pure acetates. The plot of the exponential prefactor versus the dielectric constant yields a single master curve for both conductivity and diffusion data. These data support the argument that mass and charge transport are thermally activated processes in the acetates, as previously observed in alcohol-based electrolytes. PMID:22145961

  18. Chemoselectivities in acetalization, thioacetalization, oxathioacetalization and azathioacetalization.

    PubMed

    Roy, Ram Kinkar; Bagaria, Priyanka; Naik, Sarala; Kavala, Veerababurao; Patel, Bhisma K

    2006-02-16

    In the present article (experimental as well theoretical) the relative yields of cyclic (O,O), (S,S), (S,O), and (S,N) acetals, formed from p-(NO2)C6H4CHO and p-(OH)C6H4CHO, are compared. Atomic charges, global electrophilicity descriptor (w) [as proposed by Parr et al., J. Am. Chem. Soc. 1999, 121, 1922] and hard-soft acid-base concept of Pearson (J. Am. Chem. Soc. 1963, 85, 3533) are used to explain the experimental observations. Although the w values can explain the yields, charge and local softness values of the interacting sites explain the plausible reaction mechanism. The bisnucleophiles chosen for acetalization are CH2(OH)-CH2(OH) (glycol), CH2(SH)-CH2(SH) (dithiol), CH2(OH)-CH2(SH) (oxathiol) and CH2(SH)-CH2(NH2) (azathiol). For p-(NO2)C6H4CHO, the experimental yield of cyclic acetals were found to follow the trend as (S,N) > (S,O) > (O,O) > (S,S), which is also supported by theoretical explanation based on the w values and applying the concept of hard-hard (i.e., charge-controlled) and soft-soft (i.e., orbital-controlled) interaction between the interacting sites of the substrates (i.e., aldehydes) and the reactants (bisnucleophiles). Similarly, for p-(OH)C6H4CHO the relative yields of cyclic acetals follow the trend (S,N) approximately (S,S) > (S,O) > (O,O). It is argued that the attack on C(CHO) (i.e., C-atom of the CHO group) in p-(NO2)C6H4CHO by O(OH) (i.e., O-atom of OH group) or N(NH2) (i.e., N-atom of NH2 group) is mainly charge-controlled but the attack on C(CHO) in p-(OH)C6H4CHO) by S(SH) (i.e., S-atom of SH group) is orbital-controlled. PMID:16466254

  19. Efficient decolorization and deproteinization using uniform polymer microspheres in the succinic acid biorefinery from bio-waste cotton (Gossypium hirsutum L.) stalks.

    PubMed

    Li, Qiang; Lei, Jiandu; Zhang, Rongyue; Li, Juan; Xing, Jianmin; Gao, Fei; Gong, Fangling; Yan, Xiaofeng; Wang, Dan; Su, Zhiguo; Ma, Guanghui

    2013-05-01

    Bio-waste cotton (Gossypium hirsutum L.) stalks were converted into succinic acid by simultaneous saccharification and fermentation (SSF) using Actinobacillus succinogenes 130Z. After 54 h SSF at 40 °C and pH 7.0, the production of succinic acid was 63 g/L, with 1.17 g/L/h productivity and 64% conversion yield. After SSF, a simple method for the decolorization and deproteinization of crude SSF broth was developed through adsorption tests of polystyrene (PSt) microspheres. Under optimized conditions (5% PSt loading (w/v), pH 4.0, 60 °C and adsorption time of 40 min), the ratios of decolorization, deproteinization and succinic acid loss ratios were 96.6, 84.5 and 4.1%, respectively. The method developed will provide a potential approach for large-scale production of succinic acid from the biomass waste. PMID:22985822

  20. Succination is Increased on Select Proteins in the Brainstem of the NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) Knockout Mouse, a Model of Leigh Syndrome.

    PubMed

    Piroli, Gerardo G; Manuel, Allison M; Clapper, Anna C; Walla, Michael D; Baatz, John E; Palmiter, Richard D; Quintana, Albert; Frizzell, Norma

    2016-02-01

    Elevated fumarate concentrations as a result of Krebs cycle inhibition lead to increases in protein succination, an irreversible post-translational modification that occurs when fumarate reacts with cysteine residues to generate S-(2-succino)cysteine (2SC). Metabolic events that reduce NADH re-oxidation can block Krebs cycle activity; therefore we hypothesized that oxidative phosphorylation deficiencies, such as those observed in some mitochondrial diseases, would also lead to increased protein succination. Using the Ndufs4 knockout (Ndufs4 KO) mouse, a model of Leigh syndrome, we demonstrate for the first time that protein succination is increased in the brainstem (BS), particularly in the vestibular nucleus. Importantly, the brainstem is the most affected region exhibiting neurodegeneration and astrocyte and microglial proliferation, and these mice typically die of respiratory failure attributed to vestibular nucleus pathology. In contrast, no increases in protein succination were observed in the skeletal muscle, corresponding with the lack of muscle pathology observed in this model. 2D SDS-PAGE followed by immunoblotting for succinated proteins and MS/MS analysis of BS proteins allowed us to identify the voltage-dependent anion channels 1 and 2 as specific targets of succination in the Ndufs4 knockout. Using targeted mass spectrometry, Cys(77) and Cys(48) were identified as endogenous sites of succination in voltage-dependent anion channels 2. Given the important role of voltage-dependent anion channels isoforms in the exchange of ADP/ATP between the cytosol and the mitochondria, and the already decreased capacity for ATP synthesis in the Ndufs4 KO mice, we propose that the increased protein succination observed in the BS of these animals would further decrease the already compromised mitochondrial function. These data suggest that fumarate is a novel biochemical link that may contribute to the progression of the neuropathology in this mitochondrial disease

  1. Contribution of the tricarboxylic acid (TCA) cycle and the glyoxylate shunt in Saccharomyces cerevisiae to succinic acid production during dough fermentation.

    PubMed

    Rezaei, Mohammad N; Aslankoohi, Elham; Verstrepen, Kevin J; Courtin, Christophe M

    2015-07-01

    Succinic acid produced by yeast during bread dough fermentation can significantly affect the rheological properties of the dough. By introducing mutations in the model S288C yeast strain, we show that the oxidative pathway of the TCA cycle and the glyoxylate shunt contribute significantly to succinic acid production during dough fermentation. More specifically, deletion of ACO1 and double deletion of ACO1 and ICL1 resulted in a 36 and 77% decrease in succinic acid levels in fermented dough, respectively. Similarly, double deletion of IDH1 and IDP1 decreased succinic acid production by 85%, while also affecting the fermentation rate. By contrast, double deletion of SDH1 and SDH2 resulted in a two-fold higher succinic acid accumulation compared to the wild-type. Deletion of fumarate reductase activity (FRD1 and OSM1) in the reductive pathway of the TCA cycle did not affect the fermentation rate and succinic acid production. The changes in the levels of succinic acid produced by mutants Δidh1Δidp1 (low level) and Δsdh1Δsdh2 (high level) in fermented dough only resulted in small pH differences, reflecting the buffering capacity of dough at a pH of around 5.1. Moreover, Rheofermentometer analysis using these mutants revealed no difference in maximum dough height and gas retention capacity with the dough prepared with S288C. The impact of the changed succinic acid profile on the organoleptic or antimicrobial properties of bread remains to be demonstrated. PMID:25828707

  2. Sphingolipids contribute to acetic acid resistance in Zygosaccharomyces bailii.

    PubMed

    Lindahl, Lina; Genheden, Samuel; Eriksson, Leif A; Olsson, Lisbeth; Bettiga, Maurizio

    2016-04-01

    Lignocellulosic raw material plays a crucial role in the development of sustainable processes for the production of fuels and chemicals. Weak acids such as acetic acid and formic acid are troublesome inhibitors restricting efficient microbial conversion of the biomass to desired products. To improve our understanding of weak acid inhibition and to identify engineering strategies to reduce acetic acid toxicity, the highly acetic-acid-tolerant yeast Zygosaccharomyces bailii was studied. The impact of acetic acid membrane permeability on acetic acid tolerance in Z. bailii was investigated with particular focus on how the previously demonstrated high sphingolipid content in the plasma membrane influences acetic acid tolerance and membrane permeability. Through molecular dynamics simulations, we concluded that membranes with a high content of sphingolipids are thicker and more dense, increasing the free energy barrier for the permeation of acetic acid through the membrane. Z. bailii cultured with the drug myriocin, known to decrease cellular sphingo-lipid levels, exhibited significant growth inhibition in the presence of acetic acid, while growth in medium without acetic acid was unaffected by the myriocin addition. Furthermore, following an acetic acid pulse, the intracellular pH decreased more in myriocin-treated cells than in control cells. This indicates a higher inflow rate of acetic acid and confirms that the reduction in growth of cells cultured with myriocin in the medium with acetic acid was due to an increase in membrane permeability, thereby demonstrating the importance of a high fraction of sphingolipids in the membrane of Z. bailii to facilitate acetic acid resistance; a property potentially transferable to desired production organisms suffering from weak acid stress. PMID:26416641

  3. The H+/O ratio of proton translocation linked to the oxidation of succinate by mitochondria. Reply to a commentary.

    PubMed

    Lehninger, A L; Reynafarje, B; Hendler, R W; Shrager, R I

    1985-11-18

    Costa, L.E., Reynafarje, B. and Lehninger, A.L. [(1984) J. Biol. Chem. 259, 4802-4811] have reported 'second-generation' measurements of the H+/O ratio approaching 8.0 for vectorial H+ translocation coupled to succinate oxidation by rat liver mitochondria. In a Commentary in this Journal [Krab, K., Soos, J. and Wikström, M. (1984) FEBS Lett. 178, 187-192] it was concluded that the measurements of Costa et al. significantly overestimated the true H+/O stoichiometry. It is shown here that the mathematical simulation on which Krab et al. based this claim is faulty and that data reported by Costa et al. had already excluded the criticism advanced by Krab et al. Also reported are new data, obtained under conditions in which the arguments of Krab et al. are irrelevant, which confirm that the H+/O ratio for succinate oxidation extrapolated to level flow is close to 8. PMID:4065321

  4. Production of succinic acid through overexpression of NAD(+)-dependent malic enzyme in an Escherichia coli mutant.

    PubMed Central

    Stols, L; Donnelly, M I

    1997-01-01

    NAD(+)-dependent malic enzyme was cloned from the Escherichia coli genome by PCR based on the published partial sequence of the gene. The enzyme was overexpressed and purified to near homogeneity in two chromatographic steps and was analyzed kinetically in the forward and reverse directions. The Km values determined in the presence of saturating cofactor and manganese ion were 0.26 mM for malate (physiological direction) and 16 mM for pyruvate (reverse direction). When malic enzyme was induced under appropriate culture conditions in a strain of E. coli that was unable to ferment glucose and accumulated pyruvate, fermentative metabolism of glucose was restored. Succinic acid was the major fermentation product formed. When this fermentation was performed in the presence of hydrogen, the yield of succinic acid increased. The constructed pathway represents an alternative metabolic route for the fermentative production of dicarboxylic acids from renewable feedstocks. PMID:9212416

  5. Identification of monomenthyl succinate, monomenthyl glutarate, and dimenthyl glutarate in nature by high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Hiserodt, Richard D; Adedeji, Jide; John, T V; Dewis, Mark L

    2004-06-01

    Menthol, menthone, and other natural compounds provide a cooling effect and a minty flavor and have found wide application in chewing gum and oral care products. Monomenthyl succinate, monomenthyl glutarate, and dimenthyl glutarate provide a cooling effect without the burning sensation associated with menthol. Additionally, because they do not have a distinct flavor, they can be used in applications other than mint flavors. Because these menthyl esters have not been reported in nature, we undertook to identify a natural source for these cooling compounds. Using high performance liquid chromatography-tandem mass spectrometry, monomenthyl succinate was identified in Lycium barbarum and Mentha piperita, and monomenthyl glutarate and dimenthyl glutarate were identified in Litchi chinesis. The identifications were based on the correlation of mass spectrometric and chromatographic retention time data for the menthyl esters in the extracts with authentic standards which resulted in a 99.980% confidence in the identifications. PMID:15161227

  6. Leaf malate and succinate accumulation are out of phase throughout the development of the CAM plant Ananas comosus.

    PubMed

    Rainha, N; Medeiros, V P; Ferreira, C; Raposo, A; Leite, J P; Cruz, C; Pacheco, C A; Ponte, D; Silva, A B

    2016-03-01

    In plants with Crassulacean Acid Metabolism (CAM), organic acids, mainly malate are crucial intermediates for carbon fixation. In this research we studied the circadian oscillations of three organic anions (malate, citrate, and succinate) in Ananas comosus, assessing the effect of season and plant development stage. Seasonal and plant development dependencies were observed. The circadian oscillations of malate and citrate were typical of CAM pathways reported in the literature. Citrate content was quite stable (25-30 μmol g(-1) FW) along the day, with a seasonal effect. Succinate was shown to have both diurnal and seasonal oscillations and also a correlation with malate, since it accumulated during the afternoon when malate content was normally at a minimum, suggesting a possible mechanistic effect between both anions in CAM and/or respiratory metabolisms. PMID:26773544

  7. Immunotoxicity of trenbolone acetate in Japanese quail

    USGS Publications Warehouse

    Quinn, M.J.; McKernan, M.; Lavoie, E.T.; Ottinger, M.A.

    2007-01-01

    Trenbolone acetate is a synthetic androgen that is currently used as a growth promoter in many meat-exporting countries. Despite industry laboratories classifying trenbolone as nonteratogenic, data showed that embryonic exposure to this androgenic chemical altered development of the immune system in Japanese quail. Trenbolone is lipophilic, persistent, and released into the environment in manure used as soil fertilizer. This is the first study to date to assess this chemical's immunotoxic effects in an avian species. A one-time injection of trenbolone into yolks was administered to mimic maternal deposition, and subsequent effects on the development and function of the immune system were determined in chicks and adults. Development of the bursa of Fabricius, an organ responsible for development of the humoral arm of the immune system, was disrupted, as indicated by lower masse, and smaller and fewer follicles at day 1 of hatch. Morphological differences in the bursas persisted in adults, although no differences in either two measures of immune function were observed. Total numbers of circulating leukocytes were reduced and heterophil-lymphocyte ratios were elevated in chicks but not adults. This study shows that trenbolone acetate is teratogenic and immunotoxic in Japanese quail, and provides evidence that the quail immune system may be fairly resilient to embryonic endocrine-disrupting chemical-induced alterations following no further exposure posthatch.

  8. Phytogenic biosynthesis and emission of methyl acetate.

    PubMed

    Jardine, Kolby; Wegener, Frederik; Abrell, Leif; van Haren, Joost; Werner, Christiane

    2014-02-01

    Acetylation of plant metabolites fundamentally changes their volatility, solubility and activity as semiochemicals. Here we present a new technique termed dynamic (13) C-pulse chasing to track the fate of C1-3 carbon atoms of pyruvate into the biosynthesis and emission of methyl acetate (MA) and CO2 . (13) C-labelling of MA and CO2 branch emissions respond within minutes to changes in (13) C-positionally labelled pyruvate solutions fed through the transpiration stream. Strong (13) C-labelling of MA emissions occurred only under pyruvate-2-(13) C and pyruvate-2,3-(13) C feeding, but not pyruvate-1-(13) C feeding. In contrast, strong (13) CO2 emissions were only observed under pyruvate-1-(13) C feeding. These results demonstrate that MA (and other volatile and non-volatile metabolites) derive from the C2,3 atoms of pyruvate while the C1 atom undergoes decarboxylation. The latter is a non-mitochondrial source of CO2 in the light generally not considered in studies of CO2 sources and sinks. Within a tropical rainforest mesocosm, we also observed atmospheric concentrations of MA up to 0.6 ppbv that tracked light and temperature conditions. Moreover, signals partially attributed to MA were observed in ambient air within and above a tropical rainforest in the Amazon. Our study highlights the potential importance of acetyl coenzyme A (CoA) biosynthesis as a source of acetate esters and CO2 to the atmosphere. PMID:23862653

  9. Polymer blends of polylactic acid (PLA) and polybutylene succinate-adipate

    NASA Astrophysics Data System (ADS)

    Ma, Wenguang

    A series of blends consisting of polylactic acid (PLA) and aliphatic succinate polyester (BionolleRTM #3000) had been prepared and investigated. The results of mechanical property investigations showed that using 20 wt% Bionolle#3000 can significantly increase the toughness of PLA. BionolleRTM #3000 also reduces the physical aging rate of PLA so blends remain tough longer. Conversely, the stiffness of BionolleRTM #3000 can be significantly increased by blending in PLA. DMA and DSC results show that PLA/BionolleRTM 3000 blends are not thermodynamically miscible, but are compatible blends. Studies have also been performed to determine the amount and rate of aerobic biodegradation of PLA/aliphatic succinate polyester blends in biologically active composting, enzymatic, and soil environments. The changes in molecular weight, molecular structure and thermal properties in the composting environment were also studied by GPC, NMR and DSC analyses. The research results showed BionolleRTM #3000 had a high degradation rate, while PLA had a low degradation rate. PLA/BionolleRTM #3000 blends had moderate degradation rates that increased with BionolleRTM #3000 content. The melt flow behavior of PLA/BionolleRTM #3000 blends has been studied by capillary rheometry. The relationship of the blends' viscosity with their composition, shear stress, shear rate, and temperature has been investigated. Power law index and activation energy of PLA, BionolleRTM #3000 and their blends have been calculated. The experimental and theoretical data can let us understand the processability of PLA/BionolleRTM #3000 blends. A scanning electron microscope (SEM) was used to investigate the morphological structure of the PLA/BionolleRTM #3000 blends. Micrographs of the samples made from different methods (blown film, extrudate and compression molding sheet) were taken; their differences in morphology were compared. For comparison, the micrographs of blend PLA/BionolleRTM #6000 was also studied. The

  10. A hybrid of ant colony optimization and minimization of metabolic adjustment to improve the production of succinic acid in Escherichia coli.

    PubMed

    Chong, Shiue Kee; Mohamad, Mohd Saberi; Mohamed Salleh, Abdul Hakim; Choon, Yee Wen; Chong, Chuii Khim; Deris, Safaai

    2014-06-01

    This paper presents a study on gene knockout strategies to identify candidate genes to be knocked out for improving the production of succinic acid in Escherichia coli. Succinic acid is widely used as a precursor for many chemicals, for example production of antibiotics, therapeutic proteins and food. However, the chemical syntheses of succinic acid using the traditional methods usually result in the production that is far below their theoretical maximums. In silico gene knockout strategies are commonly implemented to delete the gene in E. coli to overcome this problem. In this paper, a hybrid of Ant Colony Optimization (ACO) and Minimization of Metabolic Adjustment (MoMA) is proposed to identify gene knockout strategies to improve the production of succinic acid in E. coli. As a result, the hybrid algorithm generated a list of knockout genes, succinic acid production rate and growth rate for E. coli after gene knockout. The results of the hybrid algorithm were compared with the previous methods, OptKnock and MOMAKnock. It was found that the hybrid algorithm performed better than OptKnock and MOMAKnock in terms of the production rate. The information from the results produced from the hybrid algorithm can be used in wet laboratory experiments to increase the production of succinic acid in E. coli. PMID:24763079

  11. Identification of Pseudomonas fluorescens Chemotaxis Sensory Proteins for Malate, Succinate, and Fumarate, and Their Involvement in Root Colonization

    PubMed Central

    Oku, Shota; Komatsu, Ayaka; Nakashimada, Yutaka; Tajima, Takahisa; Kato, Junichi

    2014-01-01

    Pseudomonas fluorescens Pf0-1 exhibited chemotactic responses to l-malate, succinate, and fumarate. We constructed a plasmid library of 37 methyl-accepting chemotaxis protein (MCP) genes of P. fluorescens Pf0-1. To identify a MCP for l-malate, the plasmid library was screened using the PA2652 mutant of Pseudomonas aeruginosa PAO1, a mutant defective in chemotaxis to l-malate. The introduction of Pfl01_0728 and Pfl01_3768 genes restored the ability of the PA2652 mutant to respond to l-malate. The Pfl01_0728 and Pfl01_3768 double mutant of P. fluorescens Pf0-1 showed no response to l-malate or succinate, while the Pfl01_0728 single mutant did not respond to fumarate. These results indicated that Pfl01_0728 and Pfl01_3768 were the major MCPs for l-malate and succinate, and Pfl01_0728 was also a major MCP for fumarate. The Pfl01_0728 and Pfl01_3768 double mutant unexpectedly exhibited stronger responses toward the tomato root exudate and amino acids such as proline, asparagine, methionine, and phenylalanine than those of the wild-type strain. The ctaA, ctaB, ctaC (genes of the major MCPs for amino acids), Pfl01_0728, and Pfl01_3768 quintuple mutant of P. fluorescens Pf0-1 was less competitive than the ctaA ctaB ctaC triple mutant in competitive root colonization, suggesting that chemotaxis to l-malate, succinate, and/or fumarate was involved in tomato root colonization by P. fluorescens Pf0-1. PMID:25491753

  12. Nanoscale Infrared, Thermal, and Mechanical Characterization of Telaprevir-Polymer Miscibility in Amorphous Solid Dispersions Prepared by Solvent Evaporation.

    PubMed

    Li, Na; Taylor, Lynne S

    2016-03-01

    Miscibility is of great interest for pharmaceutical systems, in particular, for amorphous solid dispersions, as phase separation can lead to a higher tendency to crystallize, resulting in a loss in solubility, decreased dissolution rate, and compromised bioavailability. The purpose of this study was to investigate the miscibility behavior of a model poorly water-soluble drug, telaprevir (TPV), with three different polymers using atomic force microscopy-based infrared, thermal, and mechanical analysis. Standard atomic force microscopy (AFM) imaging together with nanoscale infrared spectroscopy (AFM-IR), nanoscale thermal analysis (nanoTA), and Lorentz contact resonance (LCR) measurements were used to evaluate the miscibility behavior of TPV with three polymers, hydroxypropyl methylcellulose (HPMC), HPMC acetate succinate (HPMCAS), and poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA), at different drug to polymer ratios. Phase separation was observed with HPMC and PVPVA at drug loadings above 10%. For HPMCAS, a smaller miscibility gap was observed, with phase separation being observed at drug loadings higher than ∼30-40%. The domain size of phase-separated regions varied from below 50 nm to a few hundred nanometers. Localized infrared spectra, nano-TA measurements, images from AFM-based IR, and LCR measurements showed clear contrast between the continuous and discrete domains for these phase-separated systems, whereby the discrete domains were drug-rich. Fluorescence microscopy provided additional evidence for phase separation. These methods appear to be promising to evaluate miscibility in drug-polymer systems with similar Tgs and submicron domain sizes. Furthermore, such findings are of obvious importance in the context of contributing to a mechanistic understanding of amorphous solid dispersion phase behavior. PMID:26859046

  13. Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach.

    PubMed

    Agrawal, Anjali; Dudhedia, Mayur; Deng, Weibin; Shepard, Kevin; Zhong, Li; Povilaitis, Edward; Zimny, Ewa

    2016-02-01

    The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process using commonly used HME polymers. Solid dispersions of compound X were prepared using polyvinyl pyrrolidone co-vinyl acetate 64 (PVP VA64), Soluplus, and hypromellose acetate succinate (HPMCAS-LF) polymers in 1:2 ratio by HME through 18 mm extruder. A mixture design was employed to study effect of type of polymer, filler (microcrystalline cellulose (MCC), lactose, and dicalcium phosphate anhydrous (DCPA)), and disintegrant (Crospovidone, croscarmellose sodium, and sodium starch glycolate (SSG)) as well as level of extrudates, filler, and disintegrant on tablet properties such as disintegration time (DT), tensile strength (TS), compactibility, and dissolution. Higher extrudate level resulted in longer DT and lower TS so 60-70% was the maximum amount of acceptable extrudate level in tablets. Fast disintegration was achieved with HPMCAS-containing tablets, whereas Soluplus- and PVP VA64-containing tablets had higher TS. Crospovidone and croscarmellose sodium were more suitable disintegrant than SSG to achieve short DT, and MCC was a suitable filler to prepare tablets with acceptable TS for each studied HME polymer. The influence of extragranular components on dissolution from tablets should be carefully evaluated while finalizing tablet composition, as it varies for each HME polymer. The developed statistical models identified suitable level of fillers and disintegrants for each studied HME polymer to achieve tablets with rapid DT (<15 min) and acceptable TS (≥1 MPa at 10-15% tablet porosity), and their predictivity was confirmed by conducting internal and external validation studies. PMID:26757898

  14. Supplemental fermented plant product (‘Manda Koso’) reduces succinate and deoxycholate, as well as elevates IgA and mucin levels, in rats fed a high-fat diet

    PubMed Central

    YANG, YONGSHOU; SITANGGANG, NOVITA VIVI; OKAZAKI, YUKAKO; TOMOTAKE, HIROYUKI; ARITA, KENTARO; ASHIDA, TAKAYUKI; KATO, NORIHISA

    2015-01-01

    ‘Manda Koso’ is a commercial fermented plant product (FPP) made from 53 types of fruits and vegetables that have been fermented for >3 years and 3 months. We hypothesized that FPP intake improves the luminal environment of rats fed a high-fat diet. Thus, the present study examined the effects of consumption of 5% FPP diet for 3 weeks on colonic luminal parameters in rats fed a 30% beef tallow diet. Food intake and body weight gain were unaffected. Consumption of the FPP diet did not influence the proportions of Bifidobacterium, Lactobacillus, Bacteroides, Prevotella or Clostridium in cecal contents. However, the FPP diet caused a significant reduction (−88%) in the level of cecal succinate, a putative inflammatory signal (P<0.01), but did not affect the levels of n-butyrate, propionate, acetate and lactate. The fecal levels of deoxycholate and hyodeoxycholate, which are toxic bile acids, were also significantly reduced by the FPP diet (P<0.05). The FPP diet significantly increased fecal immunoglobulin A and mucins responsible for intestinal immune and barrier functions (P<0.05). The results suggest that the consumption of FPP is beneficial for the colonic luminal environment in rats fed a high-fat diet. PMID:26623016

  15. Phytoglycogen octenyl succinate, an amphiphilic carbohydrate nanoparticle, and epsilon-polylysine to improve lipid oxidative stability of emulsions.

    PubMed

    Scheffler, Siqi L; Wang, Xue; Huang, Lei; San-Martin Gonzalez, Fernanda; Yao, Yuan

    2010-01-13

    Phytoglycogen octenyl succinate (PG-OS) and epsilon-polylysine (EPL) were used to form oil-in-water emulsions with enhanced lipid oxidative stability. PG-OS is an amphiphilic carbohydrate nanoparticle prepared using octenyl succinate (OS) substitution of phytoglycogen (PG). PG-OS had a dispersed molecular density nearly 20 times that of waxy corn starch octenyl succinate (WCS-OS). Fish oil-in-water emulsions were prepared using PG-OS, WCS-OS, and Tween 20, stored at 55 degrees C for 6 days, and monitored for the accumulation of hydroperoxide and thiobarbituric acid reactive substances (TBARS). The result indicated that PG-OS may lead to high lipid oxidative stability, and that the addition of EPL may further improve the oxidative stability of emulsions. To address the interaction between PG-OS and EPL, zeta-potential was determined for various systems. The results indicated a possible formation of an interfacial complex layer comprising both PG-OS and EPL. This complex layer may provide both physical and electrostatic barriers against pro-oxidative compounds. PMID:19928899

  16. Bagasse hydrolyzates from Agave tequilana as substrates for succinic acid production by Actinobacillus succinogenes in batch and repeated batch reactor.

    PubMed

    Corona-González, Rosa Isela; Varela-Almanza, Karla María; Arriola-Guevara, Enrique; Martínez-Gómez, Álvaro de Jesús; Pelayo-Ortiz, Carlos; Toriz, Guillermo

    2016-04-01

    The aim of this work was to obtain fermentable sugars by enzymatic or acid hydrolyses of Agave tequilana Weber bagasse in order to produce succinic acid with Actinobacillus succinogenes. Hydrolyses were carried out with mineral acids (sulfuric and hydrochloric acids) or a commercial cellulolytic enzyme, and were optimized statistically by a response surface methodology, having as factors the concentration of acid/enzyme and time of hydrolysis. The concentration of sugars obtained at optimal conditions for each hydrolysis were 21.7, 22.4y 19.8g/L for H2SO4, HCl and the enzymatic preparation respectively. Concerning succinic acid production, the enzymatic hydrolyzates resulted in the highest yield (0.446g/g) and productivity (0.57g/Lh) using A. succinogenes in a batch reactor system. Repeated batch fermentation with immobilized A. succinogenes in agar and with the enzymatic hydrolyzates resulted in a maximum concentration of succinic acid of 33.6g/L from 87.2g/L monosaccharides after 5 cycles in 40h, obtaining a productivity of 1.32g/Lh. PMID:26802183

  17. Catabolite repression in Pseudomonas aeruginosa PAO1 regulates the uptake of C4 -dicarboxylates depending on succinate concentration.

    PubMed

    Valentini, Martina; Lapouge, Karine

    2013-06-01

    In Pseudomonas aeruginosa carbon catabolite repression (CCR) is exerted by the CbrA/B-CrcZ-Crc global regulatory system. Crc is a translational repressor that, in the presence of preferred carbon sources, such as C4 -dicarboxylates, impairs the utilization of less preferred substrates. When non-preferred substrates are present, the CrcZ sRNA levels increase leading to Crc capture, thereby allowing growth of the bacterium at the expense of the non-preferred substrates. The C4 -dicarboxylate transport (Dct) system in P. aeruginosa is composed of two main transporters: DctA, more efficient at mM succinate concentrations, and DctPQM, more important at μM. In this study, we demonstrate that the Dct transporters are differentially regulated by Crc, depending on the concentration of succinate. At high concentrations, Crc positively regulates the expression of the dctA transporter gene and negatively regulates dctPQM post-transcriptionally. The activation of dctA is explained by a Crc-mediated repression of dctR, encoding a transcriptional repressor of dctA. At low succinate concentrations, Crc regulation is impaired. In this condition, CrcZ levels are higher and therefore more Crc proteins are sequestered, decreasing the amount of Crc available to perform CCR on dctR and dctPQM. As a result, expression of dctA is reduced and that of dctPQM is increased. PMID:23253107

  18. Enhancement of succinate production by metabolically engineered Escherichia coli with co-expression of nicotinic acid phosphoribosyltransferase and pyruvate carboxylase.

    PubMed

    Ma, Jiangfeng; Gou, Dongmei; Liang, Liya; Liu, Rongming; Chen, Xu; Zhang, Changqing; Zhang, Jiuhua; Chen, Kequan; Jiang, Min

    2013-08-01

    Escherichia coli BA002, in which the ldhA and pflB genes are deleted, cannot utilize glucose anaerobically due to the inability to regenerate NAD(+). To restore glucose utilization, overexpression of nicotinic acid phosphoribosyltransferase (NAPRTase) encoded by the pncB gene, a rate-limiting enzyme of NAD(H) synthesis pathway, resulted in a significant increase in cell mass and succinate production under anaerobic conditions. However, a high concentration of pyruvate accumulated. Thus, co-expression of NAPRTase and the heterologous pyruvate carboxylase (PYC) of Lactococcus lactis subsp. cremoris NZ9000 in recombinant E. coli BA016 was investigated. The total concentration of NAD(H) was 9.8-fold higher in BA016 than in BA002, and the NADH/NAD(+) ratio decreased from 0.60 to 0.04. Under anaerobic conditions, BA016 consumed 17.50 g l(-1) glucose and produced 14.08 g l(-1) succinate with a small quantity of pyruvate. Furthermore, when the reducing agent dithiothreitol or reduced carbon source sorbitol was added, the cell growth and carbon source consumption rate of BA016 was reasonably enhanced and succinate productivity increased. PMID:23740313

  19. Succinic acid-based leaching system: A sustainable process for recovery of valuable metals from spent Li-ion batteries

    NASA Astrophysics Data System (ADS)

    Li, Li; Qu, Wenjie; Zhang, Xiaoxiao; Lu, Jun; Chen, Renjie; Wu, Feng; Amine, Khalil

    2015-05-01

    A hydrometallurgical method involving natural organic acid leaching has been developed for recovery of lithium and cobalt from the cathode active materials in spent lithium-ion batteries. Succinic acid is employed as leaching agent and H2O2 as reductant. The cobalt and lithium contents from the succinic acid-based treatment of spent batteries are determined by inductively coupled plasma-optical emission spectroscopy to calculate the leaching efficiency. The spent LiCoO2 samples after calcination and the residues after leaching are characterized by X-ray diffraction and scanning electron microscopy. The results show that nearly 100% of cobalt and more than 96% of lithium are leached under optimal conditions: succinic acid concentration of 1.5 mol L-1, H2O2 content of 4 vol.%, solid-to-liquid ratio of 15 g L-1, temperature of 70 °C, and reaction time of 40 min. Results are also given for fitting of the experimental data to acid leaching kinetic models.

  20. Stability of methylprednisolone sodium succinate in small volumes of 5% dextrose and 0. 9% sodium chloride injections

    SciTech Connect

    Townsend, R.J.; Puchala, A.H.; Nail, S.L.

    1981-09-01

    The stability of methylprednisolone sodium succinate in small volumes of 5% dextrose and 0.9% sodium chloride injections was studied. Vials of methylprednisolone sodium succinate (125-3000 mg) were reconstituted and added to 50- and 100-ml volumes of the two diluents. These piggyback solutions were visually inspected for the development of haze over a 24-hour period. A nephelometer was used to quantitate the development of turbidity with time. The effect of pH on haze formation was investigated, and infrared spectroscopy was used to identify the haze. Nephelometer readings were found to correlate well with visual inspections. The haze was identified as being formed by the precipitation of free methylprednisolone. The rate of change of turbidity was directly related to the pH. A 1.4-3.2 percentage-point increase in the free methylprednisolone concentration secondary to hydrolysis over the 24-hour period was noted. The duration of stability was variable among the investigated lots and concentrations. Nineteen of the 24 admixtures stored at room temperature remained stable and free of visible haze for at least 12 hours after preparation. For all dosage strengths of methylprednisolone sodium succinate studied, these data indicate that solutions can be made stable for at least 12 hours by selecting the appropriate volume of diluent.

  1. Mechanical properties and crystallization behavior of hydroxyapatite/poly(butylenes succinate) composites.

    PubMed

    Guo, Wenmin; Zhang, Yihe; Zhang, Wei

    2013-09-01

    Biodegradable synthetic polymers have attracted much attention nowadays, and more and more researches have been done on biodegradable polymers due to their excellent mechanical properties, biocompatibility, and biodegradability. In this work, hydroxyapatite (HA) particles were melt-mixing with poly (butylenes succinate) (PBS) to prepare the material, which could be used in the biomedical industry. To develop high-performance PBS for cryogenic engineering applications, it is necessary to investigate the cryogenic mechanical properties and crystallization behavior of HA/PBS composites. Cryogenic mechanical behaviors of the composites were studied in terms of tensile and impact strength at the glass transition temperature (-30°C) and compared to their corresponding behaviors at room temperature. With the increase of HA content, the crystallization of HA/PBS composites decreased and crystallization onset temperature shifted to a lower temperature. The diameter of spherulites increased at first and decreased with a further HA content. At the same time, the crystallization rate became slow when the HA content was no more than 15wt% and increased when HA content reached 20wt%. In all, the results we obtained demonstrate that HA/PBS composites reveal a better tensile strength at -30°C in contrast to the strength at room temperature. HA particles with different amount affect the crystallization of PBS in different ways. PMID:23348918

  2. The production of succinic acid by yeast Yarrowia lipolytica through a two-step process.

    PubMed

    Kamzolova, Svetlana V; Vinokurova, Natalia G; Shemshura, Olga N; Bekmakhanova, Nadiya E; Lunina, Julia N; Samoilenko, Vladimir A; Morgunov, Igor G

    2014-09-01

    The production of α-ketoglutaric acid by yeast Yarrowia lipolytica VKMY-2412 from ethanol and its subsequent chemical conversion to succinic acid (SA) were investigated. A highly effective and environmentally friendly process of α-ketoglutaric acid production was developed using a special pH-controlling strategy, in which the titration of the culture broth with KOH in the acid-formation phase was minimal, that allowed accumulation of only low amounts of inorganic wastes in the course of SA recovery. The culture broth filtrate containing α-ketoglutaric acid (88.7 g l(-1)) was directly employed for SA production; the amount of SA produced comprised 71.7 g l(-1) with the yield of 70% from ethanol consumed. SA was isolated from the culture broth filtrate in a crystalline form with the purity of 100%. The yield of isolated SA was as high as 72% of its amount in the culture broth filtrate. The antimicrobial and nematocidic effects of SA of microbial origin on pathogenic organisms that cause human and plant diseases were revealed for the first time. PMID:24972816

  3. Neuropsychiatric Morbidity in Adolescent and Adult Succinic Semialdehyde Dehydrogenase Deficiency Patients

    PubMed Central

    Knerr, Ina; Gibson, K. Michael; Jakobs, Cornelis; Pearl, Phillip L.

    2008-01-01

    Introduction Succinic semialdehyde dehydrogenase (SSADH) deficiency (γ-hydroxybutyric aciduria) is a rare neurometabolic disorder of γ-aminobutyric acid degradation. While neurological manifestations, such as developmental delay, are typical during infancy, limited data are available on adolescent and adult symptomatology. Methods We overview the phenotype of 33 adolescents and adults (10.1–39.5 years of age, mean: 17.1 years, 48% females) with SSADH deficiency. For this purpose, we applied a database with systematic questionnaire-based follow-up data. Results Two thirds of patients (n=21) presented by 6 months of age, 14% from 6–12 months of age, 5% from 1–2 years of age, and 14% from 2–4 years of age, mean age at first symptoms was 11±12 months. However, mean age at diagnosis was 6.6±6.4 years of age. Presenting symptoms encompassed motor delay, hypotonia, speech delay, autistic features, seizures, and ataxia. Eighty-two percent demonstrated behavioral problems, such as attention deficit, hyperactivity, anxiety, or aggression, and 33% had ≥3 behavior problems. Electroencephalograms showed background slowing or epileptiform discharges in 40% of patients. Treatment approaches are then summarized. Conclusion The variable phenotype in SSADH deficiency suggests the likelihood that this disease may be under-diagnosed. Families of patients with SSADH deficiency should be counseled and supported regarding the anticipated persistence of various neuropsychiatric symptoms into adulthood. PMID:18622364

  4. Dispersion of multi-walled carbon nanotubes in biodegradable poly(butylene succinate) matrix.

    PubMed

    Ray, Suprakas Sinha; Vaudreuil, Sébastien; Maazouz, Abderrahim; Bousmina, Mosto

    2006-07-01

    This communication describes the preparation, characterization and properties of biodegradable poly(butylene succinate) (PBS)/multi-walled carbon nanotubes (MWCNTs) nanocomposite. Nanocomposite was prepared by melt-blending in a batch mixer and the amount of MWCNTs loading was 3 wt%. State of dispersion-distribution of the MWCNTs in the PBS matrix was examined by scanning and transmission electron microscopic observations that revealed homogeneous distribution of stacked MWCNTs in PBS matrix. The investigation of the thermomechanical behavior was performed by dynamic mechanical thermal analysis. Results demonstrated substantial enhancement in the mechanical properties of PBS, for example, at room temperature, storage flexural modulus increased from 0.64 GPa for pure PBS to 1.2 GPa for the nanocomposite, an increase of about 88% in the value of the elastic modulus. The tensile modulus and thermal stability of PBS were moderately improved after nanocomposite preparation with 3 wt% of MWCNTs, while electrical conductivity of neat PBS dramatically increased after nanocomposite formation. For example, the in plane conductivity increased from 5.8 x 10(-9) S/cm for neat PBS to 4.4 x 10(-3) for nanocomposite, an increase of 10(6) fold in value of the electrical conductivity. PMID:17025148

  5. Aerogel Poly(butylene succinate) Biomaterial Substrate for RF and Microwave Applications

    NASA Astrophysics Data System (ADS)

    Habib Ullah, M.; Mahadi, W. N. L.; Latef, T. A.

    2015-08-01

    Polybutylene succinate (PBS) has become a potential candidate, similar to polypropylene (PP) and acrylonitrile butadiene styrene (ABS), for use as an organic plastic material due to its outstanding mechanical properties as well as high thermal deformation characteristics. A new composition of silica aerogel nanoparticles extracted from rice waste with PBS is proposed for use as a dielectric (ɛr = 4.5) substrate for microwave applications. A microstrip patch antenna was fabricated on the proposed dielectric substrate for multi-resonant ultra-wideband (UWB) applications. The performance characteristics of the proposed biomaterial-based antenna were investigated in a far-field measurement environment. The results indicate that the proposed biocompatible material-based antenna covered a bandwidth of 9.4 (2.3-11.7) GHz with stop bands from 5.5 GHz to 5.8 GHz and 7.0 GHz to 8.3 GHz. Peak gains of 9.82 dBi, 7.59 dBi, 8.0 dBi and 7.68 dBi were measured at resonant frequencies of 2.7 GHz, 4.6 GHz, 6.3 GHz and 9.5 GHz, respectively.

  6. Surface reconstruction and hemocompatibility improvement of a phosphorylcholine end-capped poly(butylene succinate) coating.

    PubMed

    Hao, Ni; Wang, Yan-Bing; Zhang, Shi-Ping; Shi, Su-Qing; Nakashima, Kenichi; Gong, Yong-Kuan

    2014-09-01

    Control over cell-material surface interactions is the key to many new and improved biomedical devices. In this study, we present a simple yet effective surface modification method that allows for the surface reconstruction and formation of cell outer membrane mimetic structure on coatings that have significantly increased hemocompatibility. To achieve this, a phosphorylcholine end-capped poly(butylene succinate) (PBS-PC) was synthesized and dip-coated on coverslips. The surface structure of the amphiphilic PBS-PC film was reconstructed by heating in a vacuum oven to obtain the less hydrophilic surface and by immersing in hot water to obtain the more hydrophilic surface. Significant changes in the surface element concentration were observed by X-ray photoelectron spectroscopy analysis and changes in surface wettability were measured by sensitive dynamic contact angle technique. Scanning electron microscope images showed different morphologies of the reconstructed surfaces. Interestingly, the reconstruction between the less hydrophilic and more hydrophilic surfaces is reversible. More importantly, both the reconstructed surfaces are stable in room condition for more than 6 months, and both the surfaces show significant improvement in hemocompatibility as revealed by protein adsorption and platelet adhesion measurements. This reversible surface reconstruction strategy and the interesting results may be significant for fabricating stable and hemocompatible surfaces on differently shaped biomedical devices. PMID:24115737

  7. Structural control of co-continuous poly(L-lactide)/poly(butylene succinate)/clay nanocomposites.

    PubMed

    Zhao, Li; Li, Yongjin; Shimizu, Hiroshi

    2009-04-01

    Poly(L-lactide) (PLLA)/poly(butylene succinate) (PBS) (55/45 w/w) blends with different amounts of nanoclay loadings were prepared using a specially designed high-shear extruder, HSE3000mini, which can reach a maximum shear rate of 4400 sec(-1). The resulted co-continuous structural morphologies were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). SEM observation revealed that through the combination of various amounts of nanoclay loadings and processing under various shear conditions, the phase size of co-continuous structures of PLLA/PBS blends can be controlled over a wide range from several tens of micrometers to submicrometers. TEM observation shows that all the nanoclays are selectively dispersed in the PBS phase. We also found that clays in low-shear processed sample were mainly located at the interface of PBS phase, while in high-shear sample, the clays were mainly located inside of the PBS phase. It was considered that the dependence of nanoclay location in the PBS phase on the shear conditions, as well as the changing of the viscosity ratio of PBS and PLLA phase with different amounts of clay loading, play important roles in controlling the phase size of the co-continuous structures of PLLA/PBS blends. PMID:19438035

  8. A study on reactive blending of (poly lactic acid) and poly (butylene succinate co adipate)

    NASA Astrophysics Data System (ADS)

    Bureepukdee, C.; Suttiruengwong, S.; Seadan, M.

    2015-07-01

    This research aims to study the blending of Polylactic acid (PLA) and Polybutylene succinate co adipate (PBSA) in order to understand the role of peroxide in free radical reaction on the compatibilization between these two biodegradable polyesters. Various ratios of PLA/PBSA blends with and without reactive agents were prepared in the twin screw extruder. Two types of peroxides, Di (tert-butylperoxyisopropyl) benzene (DTBP) and 2, 5-Dimethyl-2, 5-(t-butylperoxy) hexane (DTBH), were used with various concentrations to compare. From the torques measurement, DTBP was more reactive with PLA and PBSA than DTBH. PLA and PBSA 80:20, 60:40, 50:50, 40:60, and 20:80% by weight were melt-blended in a twin screw extruder. The reactive polymer blends were also prepared for the same ratios of the blends with addition of 0.08 and 0.1 phr of DTBP. The mechanical, thermal, rheological, and morphological properties were investigated. The impact strengths of the non-reactive blend increased with the increasing in PBSA content. The optimal impact strength was obtained at 40%wt of PBSA with 0.1 phr of DTBP. Adding 0.08 and 0.1 phr of DTBP led to the co continuous phase morphology of PLA/PBSA blends. The per cent crystallinity of PLA increased when blended with PBSA. PBSA might induce the crystallization of PLA.

  9. Biocompatibility of a novel poly(butyl succinate) and polylactic acid blend.

    PubMed

    Kun, Hua; Wei, Zhang; Xuan, Liu; Xiubin, Yang

    2012-01-01

    A novel poly(butyl succinate) (PBS) and polylactic acid (PLA) blend with the favorable mechanical and degradable properties may be applied in the field of biomedicine. The purpose of this study was to investigate the in vitro and in vivo biocompatibilities of the PBS/PLA blend for future application. For in vitro analysis, the L929 fibroblasts and bone marrow stem cells (BMSCs) had been chosen to assess the cytocompatibility. The extract of PBS/PLA blend did not show any cytotoxicity to the L929 and BMSCs by Cell Counting Kit-8 and lactate dehydrogenase assays. Meanwhile, the results of the cytocompatibility showed no difference between the PBA/PLA blend and pure PLA and PBS. Subsequently, they were implanted into rats subcutaneously for in vivo study. It was found that similar with pure PLA and PBS, PBS/PLA blend caused the mild inflammation and foreign body reaction in rats during the consecutive 9 month implantation. However, the status of fibrosis surrounding PBS/PLA blend was superior to the pure PLA and PBS. In all, it was demonstrated that the novel PBS/PLA blend had excellent biocompatibilities in vitro and in vivo. PMID:22285977

  10. Antimicrobial activity of electrospun poly(butylenes succinate) fiber mats containing PVP-capped silver nanoparticles.

    PubMed

    Tian, Ligang; Wang, Pingli; Zhao, Zhiguo; Ji, Junhui

    2013-12-01

    In this study, biodegradable poly(butylenes succinate) (PBS) fiber mats containing silver nanoparticles (AgNPs) were prepared by the electrospinning process. Small AgNPs (<10 nm) were simply synthesized using polyvinylpyrrolidone as the capping agent as well as the reductant. The morphology of the PBS-AgNPs fiber mats and the distribution of the AgNPs were well characterized by TEM and SEM. The release of Ag from the PBS fiber mats was quantitively determined by ICP. The PBS fiber mats with 0.29 % AgNPs content showed strong antimicrobial activity against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli with the efficacy as high as 99 %. The effective bactericidal activity on E. coli was demonstrated for a short contacting time with the PBS-AgNPs fiber mats. In addition, the long-term release performance of Ag from the fiber mats can keep inhibiting the bacterial growth in the mats over a long period of time. PMID:24013858

  11. Development of micropatterned surfaces of poly(butylene succinate) by micromolding for guided tissue engineering.

    PubMed

    Coutinho, Daniela F; Gomes, Manuela E; Neves, Nuno M; Reis, Rui L

    2012-04-01

    Native tissues present complex architectures at the micro- and nanoscale that dictate their biological function. Several microfabrication techniques have been employed for engineering polymeric surfaces that could replicate in vitro these micro- and nanofeatures. In this study, biomimetic surfaces of poly(butylene succinate) (PBS) were engineered by a micromolding technique. After the optimization of the system parameters, 20 surfaces with different combinations of groove and ridge sizes were developed and characterized by scanning electron microscopy (SEM). The influence of the engineered microfeatures over the viability and attachment of human adipose derived adult stem cells (hASCs) was evaluated. hASCs cultured onto the engineered surfaces were demonstrated to remain viable for all tested patterns. SEM and immunostaining showed adequate attachment and spreading of the stem cells for all the patterned groove/ridge combinations. This study indicated that it is possible to engineer micropatterned surfaces of PBS and that the developed structures could have great potential for tissue engineering where cell alignment is an essential requisite. PMID:22266028

  12. Aerogel Poly(butylene succinate) Biomaterial Substrate for RF and Microwave Applications

    PubMed Central

    Habib Ullah, M.; Mahadi, W. N. L.; Latef, T. A.

    2015-01-01

    Polybutylene succinate (PBS) has become a potential candidate, similar to polypropylene (PP) and acrylonitrile butadiene styrene (ABS), for use as an organic plastic material due to its outstanding mechanical properties as well as high thermal deformation characteristics. A new composition of silica aerogel nanoparticles extracted from rice waste with PBS is proposed for use as a dielectric (εr = 4.5) substrate for microwave applications. A microstrip patch antenna was fabricated on the proposed dielectric substrate for multi-resonant ultra-wideband (UWB) applications. The performance characteristics of the proposed biomaterial-based antenna were investigated in a far-field measurement environment. The results indicate that the proposed biocompatible material-based antenna covered a bandwidth of 9.4 (2.3–11.7) GHz with stop bands from 5.5 GHz to 5.8 GHz and 7.0 GHz to 8.3 GHz. Peak gains of 9.82 dBi, 7.59 dBi, 8.0 dBi and 7.68 dBi were measured at resonant frequencies of 2.7 GHz, 4.6 GHz, 6.3 GHz and 9.5 GHz, respectively. PMID:26238975

  13. Dispersion analysis of polarized bulk reflectance spectra of potassium hydrogen succinate monocrystal.

    PubMed

    Klanjšek-Gunde, Marta; Ivanovski, Vladimir; Orel, Boris

    2011-09-01

    Reflectance spectra may show very different and interesting shapes. The most interesting may be connected to Evans holes. Model calculations to reproduce this effect were done applying model dielectric function functions. When a weak oscillator appears within the frequency region of a strong one (i.e. between its TO and LO frequencies), its LO-mode frequency shifts towards higher wavenumbers. As a consequence, the oscillator strength of the corresponding weak mode becomes negative which produces a dip (Evans hole) in the reflectance spectrum. This model was successfully applied to analyze polarized reflectance spectra of potassium hydrogen succinate monocrystal in the ac crystal plane. The crystal symmetry was described by phenomenological model and by full symmetry consideration. The phenomenological approach applies the four-parametric model for dielectric function which allows good evaluation of asymmetric reflectance bands. A cosine dependence of oscillator strength on polarization angle was obtained for some bands, most likely due to small deviation of the crystal symmetry from orthorhombic. This is why the phenomenological approach provides good parameters for almost all phonon modes. The full symmetry consideration applies real description of dielectric tensor in the ac plane and the three-parameter model for dielectric function. This model could give very accurate directions of transition dipole moments, but cannot fit asymmetric bands well to measured reflectance. Both approaches describe all basic spectral features, the wide reflectance of asOH and the two Evans holes appearing on its shoulder. PMID:24062113

  14. Investigation on growth, structure and characterization of succinate salt of 8-hydroxyquinoline: An organic NLO crystal

    NASA Astrophysics Data System (ADS)

    Thirumurugan, R.; Babu, B.; Anitha, K.; Chandrasekaran, J.

    2015-04-01

    8-Hydroxyquinolinium succinate (8-HQSU) has been synthesized and single crystals were grown from ethanol solvent by employing the technique of slow evaporation at room temperature. The structure of the grown crystal has been elucidated by single crystal X-ray diffraction analysis. It reveals that 8-HQSU crystallizes in monoclinic system with non-centro symmetric space group P21. FTIR, 1H and 13C NMR spectral investigations have been carried out to identify the vibrational modes of various functional groups and placement of proton and carbon in the 8-HQSU compound, respectively. UV-vis-NIR transmission spectrum shows the cutoff wavelength around 357 nm. In addition, a photoluminescence spectral analysis was carried out for 8-HQSU crystals. The thermal properties of crystals were evaluated from TGA and DTA techniques and the crystal was found to be stable up to 145 °C. The dielectric studies show that the dielectric constant and dielectric loss decrease exponentially with frequency at different temperatures. Photoconductivity studies were carried out on the grown crystals it reveals the positive photo conducting nature. Powder second harmonic generation property of the crystal was confirmed by Kurtz and Perry powder SHG technique and it is found to be 1.3 times greater than that of KDP.

  15. Tocopherol Succinate: Modulation of Antioxidant Enzymes and Oncogene Expression, and Hematopoietic Recovery

    SciTech Connect

    Singh, Vijay K.; Parekh, Vaishali I.; Brown, Darren S.; Kao, Tzu-Cheg; Mog, Steven R.

    2011-02-01

    Purpose: A class of naturally occurring isoforms of tocopherol (tocols) was shown to have varying degrees of protection when administered before radiation exposure. We recently demonstrated that {alpha}-tocopherol succinate (TS) is a potential radiation prophylactic agent. Our objective in this study was to further investigate the mechanism of action of TS in mice exposed to {sup 60}Co {gamma}-radiation. Methods and Materials: We evaluated the effects of TS on expression of antioxidant enzymes and oncogenes by quantitative RT-PCR in bone marrow cells of {sup 60}Co {gamma}-irradiated mice. Further, we tested the ability of TS to rescue and repopulate hematopoietic stem cells by analyzing bone marrow cellularity and spleen colony forming unit in spleen of TS-injected and irradiated mice. Results: Our results demonstrate that TS modulated the expression of antioxidant enzymes and inhibited expression of oncogenes in irradiated mice at different time points. TS also increased colony forming unit-spleen numbers and bone marrow cellularity in irradiated mice. Conclusions: Results provide additional support for the observed radioprotective efficacy of TS and insight into mechanisms.

  16. Development of emulsifying property in Persian gum using octenyl succinic anhydride (OSA).

    PubMed

    Mohammadi, S; Abbasi, S; Scanlon, M G

    2016-08-01

    In the present study, the influence of octenyle succinic anhydride (OSA),gum concentration, pH, temperature and reaction time on esterification of Persian gum (PG), and its soluble (SFPG) and insoluble (IFPG) fractions, were investigated by response surface methodology (RSM) in order to optimize the reaction conditions based on the degree of substitution (DS). The individual effect of all independent variables as well as the interactive effects of temperature-OSA concentration, and OSA-PG concentrations on DS was significant. However, the latter interactive effect (OSA-SFPG) was not significant in case of SFPG. The IFPG did not have any esterification reaction with OSA. The highest DS for PG and SFPG were 0.0285 and 0.0303 at the optimal conditions, respectively. The FTIR spectrums also confirmed the carbonyl group attachment in OSA-PG and OSA-SFPG. The enhancement of emulsifying capability was also confirmed by ECI and EAI values, microscopic images as well as rheological measurements. PMID:27138859

  17. Human brain aldehyde reductases: relationship to succinic semialdehyde reductase and aldose reductase.

    PubMed

    Hoffman, P L; Wermuth, B; von Wartburg, J P

    1980-08-01

    Human brain contains multiple forms of aldehyde-reducing enzymes. One major form (AR3), as previously shown, has properties that indicate its identity with NADPH-dependent aldehyde reductase isolated from brain and other organs of various species; i.e., low molecular weight, use of NADPH as the preferred cofactor, and sensitivity to inhibition by barbiturates. A second form of aldehyde reductase ("SSA reductase") specifically reduces succinic semialdehyde (SSA) to produce gamma-hydroxybutyrate. This enzyme form has a higher molecular weight than AR3, and uses NADH as well as NADPH as cofactor. SSA reductase was not inhibited by pyrazole, oxalate, or barbiturates, and the only effective inhibitor found was the flavonoid quercetine. Although AR3 can also reduce SSA, the relative specificity of SSA reductase may enhance its in vivo role. A third form of human brain aldehyde reductase, AR2, appears to be comparable to aldose reductases characterized in several species, on the basis of its activity pattern with various sugar aldehydes and its response to characteristic inhibitors and activators, as well as kinetic parameters. This enzyme is also the most active in reducing the aldehyde derivatives of biogenic amines. These studies suggest that the various forms of human brain aldehyde reductases may have specific physiological functions. PMID:6778961

  18. Biodegradable mesoporous calcium-magnesium silicate-polybutylene succinate scaffolds for osseous tissue engineering.

    PubMed

    Zhang, Xinxin; Zhang, Chi; Xu, Wei; Zhong, Biao; Lin, Feng; Zhang, Jian; Wang, Quanxiang; Ji, Jiajin; Wei, Jie; Zhang, Yang

    2015-01-01

    The structural features of bone engineering scaffolds are expected to exhibit osteoinductive behavior and promote cell adhesion, proliferation, and differentiation. In the present study, we employed synthesized ordered mesoporous calcium-magnesium silicate (om-CMS) and polybutylene succinate (PBSu) to develop a novel scaffold with potential applications in osseous tissue engineering. The characteristics, in vitro bioactivity of om-CMS/PBSu scaffold, as well as the cellular responses of MC3T3-E1 cells to the composite were investigated. Our results showed that the om-CMS/PBSu scaffold possesses a large surface area and highly ordered channel pores, resulting in improved degradation and biocompatibility compared to the PBSu scaffold. Moreover, the om-CMS/PBSu scaffold exhibited significantly higher bioactivity and induced apatite formation on its surface after immersion in the simulated body fluid. In addition, the om-CMS/PBSu scaffold provided a high surface area for cell attachment and released Ca, Mg, and Si ions to stimulate osteoblast proliferation. The unique surface characteristics and higher biological efficacy of the om-CMS/PBSu scaffold suggest that it has great potential for being developed into a system that can be employed in osseous tissue engineering. PMID:26604746

  19. Crystal structure of allyl­ammonium hydrogen succinate at 100 K

    PubMed Central

    Dziuk, Błażej; Zarychta, Bartosz; Ejsmont, Krzysztof

    2014-01-01

    The asymmetric unit of the title compound, C2H8N+·C4H5O4 −, consists of two allyl­ammonium cations and two hydrogen succinate anions (Z′ = 2). One of the cations has a near-perfect syn-periplanar (cis) conformation with an N—C—C—C torsion angle of 0.4 (3)°, while the other is characterized by a gauche conformation and a torsion angle of 102.5 (3)°. Regarding the anions, three out of four carboxilic groups are twisted with respect to the central C–CH2–CH2–C group [dihedral angles = 24.4 (2), 31.2 (2) and 40.4 (2)°], the remaining one being instead almost coplanar, with a dihedral angle of 4.0 (2)°. In the crystal, there are two very short, near linear O—H⋯O hydrogen bonds between anions, with the H atoms shifted notably from the donor O towards the O⋯O midpoint. These O—H⋯O hydrogen bonds form helical chains along the [011] which are further linked to each other through N—H⋯O hydrogen bonds (involving all the available NH groups), forming layers lying parallel to (100). PMID:25309251

  20. Novel bioactive polyester scaffolds prepared from unsaturated resins based on isosorbide and succinic acid.

    PubMed

    Smiga-Matuszowicz, Monika; Janicki, Bartosz; Jaszcz, Katarzyna; Łukaszczyk, Jan; Kaczmarek, Marcin; Lesiak, Marta; Sieroń, Aleksander L; Simka, Wojciech; Mierzwiński, Maciej; Kusz, Damian

    2014-12-01

    In this study new biodegradable materials obtained by crosslinking poly(3-allyloxy-1,2-propylene succinate) (PSAGE) with oligo(isosorbide maleate) (OMIS) and small amount of methyl methacrylate were investigated. The porous scaffolds were obtained in the presence of a foaming system consisted of calcium carbonate/carboxylic acid mixture, creating in situ porous structure during crosslinking of liquid formulations. The maximum crosslinking temperature and setting time, the cured porous materials morphology as well as the effect of their porosity on mechanical properties and hydrolytic degradation process were evaluated. It was found that the kind of carboxylic acid used in the foaming system influenced compressive strength and compressive modulus of porous scaffolds. The MTS cytotoxicity assay was carried out for OMIS using hFOB1.19 cell line. OMIS resin was found to be non-toxic in wide range of concentrations. On the ground of scanning electron microscopy (SEM) observations and energy X-ray dispersive analysis (EDX) it was found that hydroxyapatite (HA) formation at the scaffolds surfaces within short period of soaking in phosphate buffer solution occurs. After 3h immersion a compact layer of HA was observed at the surface of the samples. The obtained results suggest potential applicability of resulted new porous crosslinked polymeric materials as temporary bone void fillers. PMID:25491802