284,731 research outputs found

    Frontal Metabolite Concentration Deficits in Opiate Dependence Relate to Substance Use, Cognition, and Self-Regulation.

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    ObjectiveProton magnetic resonance spectroscopy (1H MRS) in opiate dependence showed abnormalities in neuronal viability and glutamate concentration in the anterior cingulate cortex (ACC). Metabolite levels in dorsolateral prefrontal cortex (DLPFC) or orbitofrontal cortex (OFC) and their neuropsychological correlates have not been investigated in opiate dependence.MethodsSingle-volume proton MRS at 4 Tesla and neuropsychological testing were conducted in 21 opiate-dependent individuals (OD) on buprenorphine maintenance therapy. Results were compared to 28 controls (CON) and 35 alcohol-dependent individuals (ALC), commonly investigated treatment-seekers providing context for OD evaluation. Metabolite concentrations were measured from ACC, DLPFC, OFC and parieto-occipital cortical (POC) regions.ResultsCompared to CON, OD had lower concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine +phosphocreatine (Cr) and myo-Inositol (mI) in the DLPFC and lower NAA, Cr, and mI in the ACC. OD, ALC, and CON were equivalent on metabolite levels in the POC and γ-aminobutyric acid (GABA) concentration did not differ between groups in any region. In OD, prefrontal metabolite deficits in ACC Glu as well as DLPFC NAA and choline containing metabolites (Cho) correlated with poorer working memory, executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC GABA and Cr correlated with substance use measures. In the OFC of OD, Glu and choline-containing metabolites were elevated and lower Cr concentration related to higher nonplanning impulsivity. Compared to 3 week abstinent ALC, OD had significant DLPFC metabolite deficits.ConclusionThe anterior frontal metabolite profile of OD differed significantly from that of CON and ALC. The frontal lobe metabolite abnormalities in OD and their neuropsychological correlates may play a role in treatment outcome and could be explored as specific targets for improved OD treatment

    Flux networks in metabolic graphs

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    A metabolic model can be represented as bipartite graph comprising linked reaction and metabolite nodes. Here it is shown how a network of conserved fluxes can be assigned to the edges of such a graph by combining the reaction fluxes with a conserved metabolite property such as molecular weight. A similar flux network can be constructed by combining the primal and dual solutions to the linear programming problem that typically arises in constraint-based modelling. Such constructions may help with the visualisation of flux distributions in complex metabolic networks. The analysis also explains the strong correlation observed between metabolite shadow prices (the dual linear programming variables) and conserved metabolite properties. The methods were applied to recent metabolic models for Escherichia coli, Saccharomyces cerevisiae, and Methanosarcina barkeri. Detailed results are reported for E. coli; similar results were found for the other organisms.Comment: 9 pages, 4 figures, RevTeX 4.0, supplementary data available (excel

    Bar coding MS2 spectra for metabolite identification

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    [Image: see text] Metabolite identifications are most frequently achieved in untargeted metabolomics by matching precursor mass and full, high-resolution MS(2) spectra to metabolite databases and standards. Here we considered an alternative approach for establishing metabolite identifications that does not rely on full, high-resolution MS(2) spectra. First, we select mass-to-charge regions containing the most informative metabolite fragments and designate them as bins. We then translate each metabolite fragmentation pattern into a binary code by assigning 1’s to bins containing fragments and 0’s to bins without fragments. With 20 bins, this binary-code system is capable of distinguishing 96% of the compounds in the METLIN MS(2) library. A major advantage of the approach is that it extends untargeted metabolomics to low-resolution triple quadrupole (QqQ) instruments, which are typically less expensive and more robust than other types of mass spectrometers. We demonstrate a method of acquiring MS(2) data in which the third quadrupole of a QqQ instrument cycles over 20 wide isolation windows (coinciding with the location and width of our bins) for each precursor mass selected by the first quadrupole. Operating the QqQ instrument in this mode yields diagnostic bar codes for each precursor mass that can be matched to the bar codes of metabolite standards. Furthermore, our data suggest that using low-resolution bar codes enables QqQ instruments to make MS(2)-based identifications in untargeted metabolomics with a specificity and sensitivity that is competitive to high-resolution time-of-flight technologies

    Automated method for study of drug metabolism

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    Commercially available equipment can be modified to provide automated system for assaying drug metabolism by continuous flow-through. System includes steps and devices for mixing drug with enzyme and cofactor in the presence of pure oxygen, dialyzing resulting metabolite against buffer, and determining amount of metabolite by colorimetric method

    In situ recovery of secondary metabolites using adsorption resins : a thesis presented in partial fulfilment of the requirements for the degree of Master of Philosophy at Massey University, Palmerston North, New Zealand

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    Almost without exception a two to three fold increase in microbial secondary metabolite concentration was measured when adsorption resins were added in-situ during a submerged liquid fermentation. Anguidine was produced at a final concentration of 440 mg/L after five days in a shake flask that contained adsorption resin, compared to 300 mg/L without resin. Rapamcyin was produced at a final concentration of 87 mg/L after six days in a shake flask that had resin present, compared to 28 mg/L without resin. Ansamitocin P3 was produced at a final concentration of 24 mg/L after six days in a shake flask with resin, compared to 9.75 mg/L without resin. The increase in secondary metabolite concentration confirmed that the resins used provided a positive influence on secondary metabolite production. Adsorption resins for shake flask studies were selected based on their ability to achieve maximum adsorption of specific secondary metabolites in various fermentation systems. A library of adsorbed concentrations was collected for the three secondary metabolites studied. The lipophilicty of the metabolite, calculated by several software packages, was compared to the polarity of the adsorption resin to generate a relationship. By using the preceding set of data it is possible to select adsorption resins that improved the produced concentrations of the target organic secondary metabolites. The fermentation media compositions tested appeared to have no effect on the final product concentration when adsorption resins were added in situ during the fermentations. Based on the lipohilictiy of the secondary metabolite and the polarity of the resins, it is possible to select a resin that achieves a high adsorption concentration of the target organic secondary metabolite

    Determination of the urinary aglycone metabolites of vitamin K by HPLC with redox-mode electrochemical detection

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    We describe a method for the determination of the two major urinary metabolites of vitamin K as the methyl esters of their agyclone structures, 2-methyl-3-(3-3-carboxymethylpropyl)-1,4-naphthoquinone (5C-side-chain metabolite) and 2-methyl-3-(5-carboxy-3-methyl-2-pentenyl)-1,4-naphthoquinone (7C-side-chain metabolite), by HPLC with electrochemical detection (ECD) in the redox mode. Urinary salts were removed by reversed-phase (C18) solid phase extraction (SPE) and the predominately conjugated vitamin K metabolites hydrolysed with methanolic HCl. The resultant carboxylic acid aglycones were quantitatively methylated with diazomethane and fractionated by normal-phase (silica) SPE. Final analysis was by reversed-phase (C18) HPLC with a methanol-aqueous mobile phase. Metabolites were detected by amperometric, oxidative ECD of their quinol forms, which were generated by post-column coulometric reduction at an upstream electrode. The assay gave excellent linearity (r2 typically = 0.999) and high sensitivity with an on-column detection limit of <3.5 fmol (<1pg). The inter-assay precision was typically 10%. Metabolite recovery was compared to that of an internal standard (2-methyl-3-(7'-carboxy-heptyl)-1,4-naphthoquinone), added to urine samples just before analysis. Using this methodology we confirmed that the 5C- and 7C-metabolite were major catabolites of both phylloquinone (vitamin K1) and menaquinones (vitamin K2) in humans. We propose that the measurement of urinary vitamin K metabolite excretion is a candidate non-invasive marker of total vitamin K status