Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GLUTARATES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources
PubMed2005

Carbon nanotube/cobalt hexacyanoferrate nanoparticle-biopolymer system for the fabrication of biosensors.

Cobalt hexacyanoferrate nanoparticles (CoNP) can be easily prepared by mixing hexacyanoferrate and cobalt chloride solution at room temperature. The nanoparticles were solubilized in aqueous solution of a biopolymer chitosan (CHIT). With the introduction of carbon nanotubes (CNT), the CoNP-CNT-CHIT system formed shows synergy between CNT and CoNP with the significant improvement of redox activity of CoNP due to the excellent electron-transfer ability of CNT. The CoNP-CNT-CHIT film modified glassy carbon electrode allows low potential detection of hydrogen peroxide with high sensitivity and fast response time. In particular, with the introduction of CNT, it amplified the H2O2 sensitivity by approximately 70 times compared to film of CoNP-CHIT. With the immobilization of glucose oxidase onto the electrode surface using glutaric dialdehyde, a biosensor that responds sensitively to glucose has been constructed. In pH 6.98 phosphate buffer, interference free determination of glucose has been realized at -0.2V versus saturated calomel electrode (SCE) with a linear range from 0.01 to 10 mM and response time<10s. The detection limit was 5 microM glucose (S/N=3).

Biocompatible Materials↗
PubMed2006

Synthesis of pyrazoles and isoxazoles as potent alpha(v)beta3 receptor antagonists.

We describe a series of pyrazole and isoxazole analogs as antagonists of the alpha(v)beta3 receptor. Compounds showed low to sub-nanomolar potency against alpha(v)beta3, as well as good selectivity against alpha(IIb)beta3. In HT29 cells, most analogs also demonstrated significant selectivity against alpha(v)beta6. Several compounds showed good pharmacokinetic properties in rats, in addition to anti-angiogenic activity in a mouse corneal micropocket model. Compounds were synthesized in a straightforward manner from readily available glutarate precursors.

Animals↗
PubMed2005

Development and validation of a reversed-phase liquid chromatography method for the quantitative determination of carboxylic acids in industrial reaction mixtures.

Usually analysis of low molecular-mass carboxylic acids was performed by anion-exchange or ion-exclusion chromatographic methods. Reversed-phase liquid chromatography (RPLC) was evaluated in this work as an alternative method for the analysis of low molecular-mass aliphatic mono- and di-carboxylic acids (formic, acetic, propionic, butyric, valeric, caproic, succinic, glutaric and adipic) in aqueous media. The separation of the nine organic acids was optimised in 21 min on a high-density C18 column with an elution gradient made up of HClO4 aqueous solution 10(-3) mol L(-1) and acetonitrile. For the quantitation, external standard and standard addition methods were compared. Both methods gave similar results, so the most convenient method, external standard, was chosen for acids quantitation. Then the method had been validated and applied to the semi-quantitative analysis of formic and acetic acids and to the quantitative analysis of the others compounds in industrial reaction mixtures with concentrations ranging from 20 to 570 ppm.

Carboxylic Acids↗
PubMed2005

Characterization of prostaglandin E1 transport by rat renal cortical slices.

The purpose of this study was to examine prostaglandin E1 (PGE1) transport in rat kidney. [3H]PGE1 administered intravenously was accumulated most abundantly in the renal cortex. Infusion of probenecid and bromcresol green (BCG) decreased [3H]PGE1 accumulation in the renal cortex after injection of [3H]PGE1. To further investigate PGE1 transport in the kidney, [3H]PGE1 uptake by renal cortical slices was examined. Probenecid and BCG inhibited [3H]PGE1 uptake by the slices. Unlabeled PGE1 decreased [3H]PGE1 uptake by renal cortical slices in a concentration-dependent manner. The inhibitory effect of various dicarboxylates with different carbon atoms on [3H]PGE1 uptake was maximal at 6 carbon atoms. Preloading cortical slices with glutarate significantly increased [3H]PGE1 uptake. [3H]PGE1 uptake was inhibited by various eicosanoids and compounds with other structures (p-aminohippurate, benzylpenicillin, estrone-3-sulfate, etc.). These findings suggest that PGE1 uptake by renal cortical slices may be mediated by the members of the organic anion transporter family.

Alprostadil↗
PubMed2005

Development of a single unit extended release formulation for ZK 811 752, a weakly basic drug.

ZK 811 752, a potent candidate for the treatment of autoimmune diseases, demonstrated pH-dependent solubility. The resulting release from conventional matrix tablets decreased with increasing pH-values of the dissolution medium. The aim of this study was to overcome this problem and to achieve pH-independent drug release. Three different polymers were used as matrix formers, the partly water-soluble and poorly swellable mixture of polyvinylacetate/polyvinylpyrrolidone, the water-insoluble and almost unswellable ethylcellulose (EC) and the water-soluble and highly swellable hydroxypropyl methylcellulose (HPMC). To solve the problem of pH-dependent solubility different organic acids, such as fumaric, tartaric, adipic, glutaric and sorbic acid were added to the drug-polymer system. The addition of organic acids to all three matrix formers was found to maintain low pH-values within the tablets during release of ZK 811 752 in phosphate buffer pH 6.8. Thus, the micro-environmental conditions for the dissolution of the weakly basic drug were kept almost constant. An extended release matrix tablet for ZK 811 752 consisting of drug, polymer and organic acid providing the desired pH-independent drug release has been developed.

Chemistry, Pharmaceutical↗
PubMed2004

Probing three-dimensional structure of bovine serum albumin by chemical cross-linking and mass spectrometry.

Serum albumin is the principal transporter of fatty acids that are otherwise insoluble in circulating plasma. While the crystal structure of human serum albumin (HSA) as well as its binding with fatty acids has been characterized, the three dimensional structure of bovine serum albumin (BSA) has not been determined although both albumins share 76% sequence homology. In this study we used mass spectrometry coupled with chemical cross-linking, to probe the tertiary structure of BSA. BSA was modified with lysine specific cross-linkers, bis(sulfosuccinimidyl) suberate (BS(3)), disuccinimidyl suberate (DSS) or disuccinimidyl glutarate (DSG), digested with trypsin and analyzed by tandem mass spectrometry. With O-18 labeling during the digestion, through-space cross-linked peptides were readily identified in mass spectra by a characteristic 8 Da shift. From the cross-linked peptides identified in this study, we found that 12 pairs of lysine residues were separated within 20 A, while 5 pairs were spaced between 20 and 24 A. The spatial distance constraints generated from five K-K pairs in BSA were consistent with the corresponding distance obtained from the crystal structure of HSA, although only six equivalent K-K pairs could be compared. According to our data, the distance between K235 of IIA and K374 of IIB domain in BSA was farther by 7-11 A than that expected from the crystal structure of HSA, suggesting structural differences between BSA and HSA in this region. The distance constraints obtained for lysine residues using various cross-linkers should be valuable in assisting the determination of the 3-D structure of BSA.

Animals↗
PubMed2006

Influence of crosslinker identity and position on gas-phase dissociation of Lys-Lys crosslinked peptides.

A systematic study of the dissociation patterns of crosslinked peptides analyzed by tandem mass spectrometry is reported. A series of 11-mer peptides was designed around either a polyalanine or polyglycine scaffold with arginine at the C terminus. One or two lysine residues were included at various locations within the peptides to effect inter- or intra-molecular crosslinking, respectively. Crosslinked species were generated with four commonly used amine-specific chemical crosslinking reagents: disuccinimidyl suberate (DSS), disuccinimidyl tartarate (DST), dithiobis(succinimidylpropionate) (DSP), and disuccinimidyl glutarate (DSG). The influence of precursor charge state, location of crosslink, and specific crosslinking reagent on the MS/MS dissociation pattern was examined. Observed trends in the dissociation patterns obtained for these species will allow for improvements to software used in the automated interpretation of crosslinked peptide MS/MS data.

Binding Sites↗
PubMed2006

Isotope-labeled cross-linkers and Fourier transform ion cyclotron resonance mass spectrometry for structural analysis of a protein/peptide complex.

For structural studies of proteins and their complexes, chemical cross-linking combined with mass spectrometry presents a promising strategy to obtain structural data of protein interfaces from low quantities of proteins within a short time. We explore the use of isotope-labeled cross-linkers in combination with Fourier transform ion cyclotron resonance (FTICR) mass spectrometry for a more efficient identification of cross-linker containing species. For our studies, we chose the calcium-independent complex between calmodulin and a 25-amino acid peptide from the C-terminal region of adenylyl cyclase 8 containing an "IQ-like motif." Cross-linking reactions between calmodulin and the peptide were performed in the absence of calcium using the amine-reactive, isotope-labeled (d0 and d4) cross-linkers BS3 (bis[sulfosuccinimidyl]suberate) and BS2G (bis[sulfosuccinimidyl]glutarate). Tryptic in-gel digestion of excised gel bands from covalently cross-linked complexes resulted in complicated peptide mixtures, which were analyzed by nano-HPLC/nano-ESI-FTICR mass spectrometry. In cases where more than one reactive functional group, e.g., amine groups of lysine residues, is present in a sequence stretch, MS/MS analysis is a prerequisite for unambiguously identifying the modified residues. MS/MS experiments revealed two lysine residues in the central alpha-helix of calmodulin as well as three lysine residues both in the C-terminal and N-terminal lobes of calmodulin to be cross-linked with one single lysine residue of the adenylyl cyclase 8 peptide. Further cross-linking studies will have to be conducted to propose a structural model for the calmodulin/peptide complex, which is formed in the absence of calcium. The combination of using isotope-labeled cross-linkers, determining the accurate mass of intact cross-linked products, and verifying the amino acid sequences of cross-linked species by MS/MS presents a convenient approach that offers the perspective to obtain structural data of protein assemblies within a few days.

Adenylyl Cyclases↗
PubMed2004

Solid phase extraction procedure for urinary organic acid analysis by gas chromatography mass spectrometry.

We have developed a solid phase extraction procedure for the detection of organic acids by GC-MS using a strong anion exchange column (Sep-Pak Vac RC, Accell Plus QMA cartridge). Extraction efficiencies of 25 organic acids were established by analyzing standards in water based solutions. High extraction efficiencies (90 to 100%) were found for many of the compounds studied. We estimated the limit of detection for 48 organic acids and glycine conjugates. They were below 5 nmole with the exception of malonic and oxalic acids and mevalonic acid lactone. This method provides the advantage of higher recoveries for a wide range of compounds of interest and therefore can be a potential alternative to liquid-liquid extraction for organic acid screening. It is especially sensitive for the detection of some polar compounds, such as 3-OH-glutaric and N-acetylaspartic acids.

Acids↗
PubMed2005

Intercalation and functionalization of zinc hydroxide nitrate with mono- and dicarboxylic acids.

The intercalation of ions derived from succinic, glutaric, and adipic acid into layered zinc hydroxide nitrate by ionic exchange reaction is reported. Different reaction conditions are investigated and the materials are characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, thermal analysis (simultaneous thermogravimetry and differential scanning calorimetry) and elemental analysis. The dicarboxylic acids can be grafted to the matrix slab by one carboxylate group and the second hydrated carboxylate group is hanging between the layers. Benzoate ions have also been intercalated by both ionic exchange reaction and stirring in acetonitrile. The two benzoate-intercalated materials exchange the organic moiety by sulfate ions if stirred in magnesium sulfate solution, but the sample obtained by anion exchange also allows the unusual incorporation of neutral magnesium sulfate in addition to free solvated sulfate ion. A schematic arrangement of the intercalated species between the layers is presented.

Journal Article↗
PubMed2004

Controlled drug release from hydrogel nanoparticle networks.

Monodisperse nanoparticles of poly-N-isopropylacrylamide-co-allylamine (PNIPAM-co-allylamine) and PNIPAM-co-acrylic acid (PNIPAM-co-AA) were synthesized. The close-packed PNIPAM-co-allylamine and PNIPAM-co-AA nanoparticles were converted to three-dimensional gel networks by covalently crosslinking neighboring particles at room temperature and neutral pH using glutaric dialdehyde and adipic acid dihydrazide, respectively. Controlled release studies were conducted using dextran markers of various molecular weights as model macromolecular drugs. Release was quantified under various physical conditions, including a range of temperatures and dextran molecular weights. Dextran, entrapped in cavities in the nanoparticle network, was released with a rate regulated by their molecular weights and cavity size. No release from a conventional bulk PNIPAM gel, with high crosslinking density, was observed. The rate of release from the PNIPAM-co-allylamine network was temperature-dependent, being much faster at room temperature than that at human body temperature. In contrast, release of low molecular weight dextrans from the PNIPAM-co-AA network showed a temperature-independent release profile. These nanoparticle networks have several advantages over conventional bulk gels for controlling the release of high molecular weight biomolecules.

Acrylic Resins↗
PubMed2006

Degradation of 17alpha-ethinylestradiol in aqueous solution by ozonation.

This study investigates the ozonation of 17alpha-ethinylestradiol (EE(2)) in aqueous solution. The affecting factors on the degradation of EE(2) were studied and described in details, such as initial EE(2) concentration, initial pH value and ozone concentration. In addition, some parameters such as pH, electrical conductivity, mineralization efficiency and degradation products were monitored during the process. The mineralization efficiency of EE(2) could reach 53.9%. During the ozonation process the rapid decrease of pH and the sharp increase of electrical conductivity indicated the formation of acidic by-products, small fragments and ions which were confirmed by high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC/MS) analysis. Results showed that there were intermediate products of smaller molecule with higher polarity produced during the course of EE(2) degradation. Then a possible reaction pathway for EE(2) degradation involving all intermediates detected is proposed. During the ozonation process EE(2) was first oxidized into hydroxyl-semiquinone isomers which were subsequently degraded into low molecular weight compounds such as oxalic acid, malonate, glutarate, and so on. Furthermore, these organic acids are easily oxidized by ozone into carbon dioxide (CO(2)). This work shows that ozonation process is promising for the removal of EE(2). The results can provide some useful information for the potential treatment of EE(2) by ozonation in aqueous solution.

Chromatography, High Pressure Liquid↗
PubMed2006

Modelling calcium carbonate biomineralisation processes.

The structure-directing influence of the organic dicarboxylates malonate, succinate, glutarate and adipate as templating species on the hydrothermal formation of CaCO(3) was investigated at different temperatures (60, 80, 90, 120, 150 and 190 degrees C) and with a range of molar ratios of [Ca(2+)]/[templating species] (20, 14.3, 10, 7.7, 5, 1, 0.5 and 0.33). In the presence of the dicarboxylates, one, two or three polymorphs of CaCO(3) - calcite, aragonite and vaterite - could be formed, depending on the reaction conditions. In addition changes in crystal morphology were observed for the CaCO(3) polymorphs depending on the concentration of the template. In contrast, synthesis under ambient conditions of temperature and pressure resulted only in calcite formation, although template-dependent morphological changes were again observed. Crystalline products were all characterized by powder X-ray patterns and SEM (Scanning Electron Microscopy) micrographs. The ambient reactions with the chelating, dinucleating carboxylato ligands H(3)heidi and H(5)hpdta produce more profound changes in calcite morphology. With H(3)heidi rounded calcite crystals with shapes similar to that of otoliths are formed and with H(5)hpdta the formation of microtrumpets of constructed from bundles of nanocrystals of calcite is observed. The possible mode of action of these ligands on calcite formation is discussed in the context of known coordination chemistry with other metal ions.

Calcium Carbonate↗
PubMed2004

Hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome with evidence of mitochondrial dysfunction due to a novel SLC25A15 (ORNT1) gene mutation in a Palestinian family.

Hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome is caused by mutations in the SLC25A15 (ORNT1) gene encoding the mitochondrial ornithine transporter, but the mechanism of pathogenesis of the encephalopathy, spastic paraparesis and hepatopathy remains undetermined. HHH syndrome was diagnosed in a 2-year-old Palestinian boy with developmental delay and seizures, and subsequently in his 13-year-old brother with developmental delay. Direct sequencing of the PCR products of SLC25A15 exon amplifications revealed that both brothers were homozygous for a novel 446G deletion in exon 3 as well as for a 760A>T (I254L) polymorphism in exon 5, which is downstream of a premature termination codon produced by the frameshift resulting from the 446G deletion. The index patient had elevated liver enzymes as well as hyperalaninemia, lactic acidemia with an elevated lactate to pyruvate ratio, and increased urinary excretion of lactate, glutarate and Krebs cycle intermediates. These findings are indicative of mitochondrial dysfunction and are in accordance with ultrastructural studies showing increased numbers of large and bizarre mitochondria in liver, muscle, leukocytes and fibroblasts of some HHH patients. Neurologic and hepatic manifestations are characteristic of some primary mitochondrial disorders. Secondary mitochondrial dysfunction may contribute to the pathogenesis of these same features in HHH syndrome.

Adolescent↗
PubMed2006

Acute metabolic crisis induced by vaccination in seven Chinese patients.

Seven Chinese patients (5 males and 2 females) with vaccination-induced acute metabolic crisis were reported. Only one male with 21-hydroxylase deficiency had been diagnosed before vaccination. In the remaining six patients, the preexisting diagnoses were not confirmed before the vaccination. Acute metabolic crisis occurred in seven patients between 3 and 12 hours after the administration of Japanese encephalitis, diphtheria, and tetanus toxoids and acellular pertussis, hepatitis B, or measles vaccines. Patients 1 and 2 displayed acute adrenal insufficiencies at the ages of 5 years and 3 months, respectively. Patient 3 had presented with mild motor retardation previously. Patients 4 to 7 were previously healthy, but suffered from fever, seizures, coma, acidosis, and hypoglycemia after being vaccinated. Glutaric aciduria type 1 was evident in case 4. Leigh syndromes were present in Patients 5, 6, and 7. They all died from respiratory failure before 2 years of age. Symmetric foci, cystic cavitations with neuronal loss, and vascular proliferation were observed by postmortem examination. Among the seven patients, although the vaccines were not the primary cause of the acute metabolic crisis, the severe acute episodes occurred coincidentally.

Acid-Base Imbalance↗
PubMed2006

The flavonoid herbacetin diglucoside as a constituent of the lignan macromolecule from flaxseed hulls.

Lignans in flaxseed are known to be part of a macromolecule in which they are connected through the linker-molecule hydroxy-methyl-glutaric acid (HMGA). In this study, the lignan macromolecule was extracted from flaxseed hulls and degraded to its monomeric constituents by complete saponification. Besides secoisolariciresinol diglucoside (SDG), the phenolic compounds p-coumaric acid glucoside (CouAG) and ferulic acid glucoside (FeAG) were isolated, which was expected based on indications from the literature. Also the flavonoid herbacetin diglucoside (HDG) was found. The presence of HDG was confirmed by NMR following preparative RP-HPLC purification. Also the presence of the three other constituents (CouAG, FeAG and SDG) was confirmed by NMR. To prove that HDG is a substructure of the lignan macromolecule, the macromolecule was fragmented by partial saponification. A fragment consisting of HDG and HMGA was indicated. This fragment was isolated by preparative RP-HPLC and its identity was confirmed by NMR. It is concluded that the flavonoid HDG is a substructure of the lignan macromolecule from flaxseed hulls and that it is incorporated in the macromolecule via the same linker-molecule as SDG.

Chemical Fractionation↗
PubMed2006

Study of a novel indolin-2-ketone compound Z24 induced hepatotoxicity by NMR-spectroscopy-based metabonomics of rat urine, blood plasma, and liver extracts.

Antiangiogenic compound has been believed to be an ideal drug in the current cancer biological therapy, but the angiogenesis inhibitors suffer setback for unknown toxicity now. A novel synthetic indolin-s-ketone small molecular compound, 3Z-3-[((1)H-pyrrol-2-yl)-methylidene]-1-(1-piperidinylmethyl)-1,3-2H-indol-2-one (Z24) can inhibit angiogenesis in new blood vessels. The hepatotoxicity effects of Z24 oral administration (dosed at 60, 130 and 200 mg/kg) have been investigated in female Wistar rats by using metabonomic analysis of (1)H NMR spectra of urine, plasma and liver extracts, as well as by clinical chemistry analysis, liver histopathology and electron micrographs examination. The (1)H NMR spectra of the biofluids were analyzed visually and via pattern recognition by using principal component analysis. The metabonomic trajectory analysis on the time-related hepatotoxicity of Z24 was carried out based on the (1)H NMR spectra of urine samples, which were collected daily predose and postdose over an 8-day period. Urinary excretion of citrate, lactate, 2-oxo-glutarate and succinate increased following Z24 dosing. Increased plasma levels of lactate, TMAO and lipid were observed, with concomitant decrease in the level of glucose and phosphatidylcholine. Metabolic profiling on aqueous soluble extracts of liver tissues with the high dose level of Z24 showed an increase in lactate and glutamine, together with a decrease in glucose, glycogen and choline. On the other hand, studies on lipid soluble extracts of liver tissues with the high dose level of Z24 showed increased level in lipid triglycerides and decreased level in unsaturated fatty acids and phosphatidylcholine. Moreover, the most notable effect of Z24 on the metabolism was the reduction in the urinary levels of creatinine and TMAO and the increase in acetate, citrate, succinate and 2-oxo-glutamate with time dependence. The results indicate that in rats Z24 inhibits mitochondrial function through altering the energy and lipid metabolism, which results in the accumulation of free fatty acids and lactate because of the lack of aerobic respiration. These data show that the metabonomic approach represents a promising new technology for the toxicological mechanism study.

Animals↗
PubMed2005

Identification of the human mitochondrial FAD transporter and its potential role in multiple acyl-CoA dehydrogenase deficiency.

Multiple acyl-CoA dehydrogenase deficiency (MADD) or glutaric aciduria type II (GAII) is most often caused by mutations in the genes encoding the alpha- or beta-subunit of electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETF-DH). Since not all patients have mutations in these genes, other as yet unidentified genes are predicted to be involved as well. Because all affected mitochondrial flavoproteins in MADD have FAD as a prosthetic group, the underlying defect in these patients may be due to a thus far undisclosed disturbance in the metabolism of FAD. Since a proper mitochondrial flavin balance is maintained by a mitochondrial FAD transporter, a defect of this transporter could also cause an MADD-like phenotype. In yeast, FAD is transported across the mitochondrial inner membrane by the FLX1 protein. An FLX1-mutated Saccharomyces cerevisiae strain exhibits a decreased activity of several mitochondrial flavoproteins. In the present study, we report the identification of the human mitochondrial FAD transporter. Based on sequence similarity to FLX1, we identified two human candidate genes (MFT and N111), which were cloned and characterized by functional expression in an FLX1-mutated yeast strain. Of the two candidate genes, only the previously described mitochondrial folate transporter (MFT) was able to functionally complement the FLX1 mutant. Candidates for mutations in the MFT gene are patients with a clinical suspicion of MADD but without any mutation in the alpha- or beta-subunit of ETF or ETF-DH.

Acyl-CoA Dehydrogenase↗