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Jeremy K. Nicholson - One of the best experts on this subject based on the ideXlab platform.

  • high resolution magic angle spinning NMR Spectroscopy for metabolic profiling of intact tissues
    Nature Protocols, 2010
    Co-Authors: Olaf Beckonert, Hector C. Keun, John C. Lindon, Muireann Coen, Yulan Wang, Timothy M D Ebbels, Elaine Holmes, Jeremy K. Nicholson
    Abstract:

    Metabolic profiling, metabolomic and metabonomic studies require robust study protocols for any large-scale comparisons and evaluations. Detailed methods for solution-state NMR Spectroscopy have been summarized in an earlier protocol. this protocol details the analysis of intact tissue samples by means of high-resolution magic-angle-spinning (HR-MAS) NMR Spectroscopy and we provide a detailed description of sample collection, preparation and analysis. Described here are (1)H NMR spectroscopic techniques such as the standard one-dimensional, relaxation-edited, diffusion-edited and two-dimensional J-resolved pulse experiments, as well as one-dimensional (31)p NMR Spectroscopy. these are used to monitor different groups of metabolites, e. g., sugars, amino acids and osmolytes as well as larger molecules such as lipids, non-invasively. Through the use of NMR-based diffusion coefficient and relaxation times measurements, information on molecular compartmentation and mobility can be gleaned. the NMR methods are often combined with statistical analysis for further metabonomics analysis and biomarker identification. the standard acquisition time per sample is 8-10 min for a simple one-dimensional (1)H NMR spectrum, giving access to metabolite information while retaining tissue integrity and hence allowing direct comparison with histopathology and MRI/MRS findings or the evaluation together with biofluid metabolic-profiling data.

  • Cryogenic probe 13C NMR Spectroscopy of urine for metabonomic studies.
    Analytical chemistry, 2002
    Co-Authors: Hector C. Keun, Olaf Beckonert, Julian L. Griffin, Christian Richter, Detlef Moskau, John C. Lindon, Jeremy K. Nicholson
    Abstract:

    Cryogenic probe technology can significantly compensate for the inherently low sensitivity of natural abundance 13C NMR Spectroscopy. This now permits its routine use in NMR Spectroscopy of biofluids, such as urine or plasma, with acquisition times that enable a high throughput of samples. Metabonomic studies often generate numerous samples in order to characterize fully the time-dependent biochemical response to stimuli, but until now, they have been largely conducted using 1H NMR Spectroscopy because of its high sensitivity and hence efficient data acquisition. Here, we demonstrate that information-rich 13C NMR spectra of rat urine can be obtained using appropriately short acquisition times suitable for biochemical samples when using a cryogenic probe. Furthermore, these data were amenable to automated pattern recognition analysis, which produced a profile of the metabolic response to the model hepatotoxin hydrazine that was consistent with earlier studies. Thus, a new source of detailed and complementa...

Ron A Wevers - One of the best experts on this subject based on the ideXlab platform.

  • defect in dimethylglycine dehydrogenase a new inborn error of metabolism NMR Spectroscopy study
    Clinical Chemistry, 1999
    Co-Authors: Sytske H Moolenaar, Barbara A Binzak, Jo Poggibach, Jerry Vockley, Jacqueline M B Corstiaensen, Jan G N De Jong, Arend Heerschap, Udo F H Engelke, Ron A Wevers
    Abstract:

    Background: A38-year-old man presented with a history of fish odor (since age 5) and unusual muscle fatigue with increased serum creatine kinase. Our aim was to identify the metabolic error in this new condition. Methods: We used 1H NMR Spectroscopy to study serum and urine from the patient. Results: The concentration of N,N-dimethylglycine (DMG) was increased ∼100-fold in the serum and ∼20-fold in the urine. The presence of DMG as a storage product was confirmed by use of 13C NMR Spectroscopy and gas chromatography–mass spectrometry. The high concentration of DMG was caused by a deficiency of the enzyme dimethylglycine dehydrogenase (DMGDH). A homozygous missense mutation was found in the DMGDH gene of the patient. Conclusions: DMGDH deficiency must be added to the differential diagnosis of patients complaining of a fish odor. This deficiency is the first inborn error of metabolism discovered by use of in vitro 1H NMR Spectroscopy of body fluids.

  • 1H NMR Spectroscopy of body fluids in patients with inborn errors of purine and pyrimidine metabolism
    Journal of Inherited Metabolic Disease, 1997
    Co-Authors: Ron A Wevers, Arend Heerschap, Udo F H Engelke, Jan J. Rotteveel, J.g.n. De Jong, R. A. De Abreu
    Abstract:

    1H NMR Spectroscopy of body fluids has been used in the diagnosis of many inborn errors of metabolism (Lehnert and Hunkler 1986; Iles and Chalmers 1988). To our knowledge there is no systematic study available of body fluids from patients with inborn errors in the purine or pyrimidine metabolism. The main advantage of the technique over others that are used diagnostically in the screening for inborn errors of metabolism is the minimal sample pretreatment required for NMR Spectroscopy. Fractionation, extraction or derivatization of metabolites is not required. A further advantage is the overall view of proton-containing metabolites. Quantification of metabolites is possible. An obvious disadvantage is the substantial cost of high-field NMR spectrometers that are required for this work. This paper demonstrates that NMR Spectroscopy can be used in diagnosing inborn errors in purine and pyrimidine metabolism. Examples are given of NMR spectra of body fluids from patients with dihydropyrimidine dehydrogenase deficiency (McKusick 274270) and with dihydropyrimidinase deficiency (McKusick 222748).

Udo F H Engelke - One of the best experts on this subject based on the ideXlab platform.

  • guanidinoacetate methyltransferase gamt deficiency diagnosed by proton NMR Spectroscopy of body fluids
    NMR in Biomedicine, 2009
    Co-Authors: Udo F H Engelke, Maria Tassini, J Hayek, Maaike De Vries, Appie Bilos, Antonio Vivi, Gianni Valensin, Sabrina Buoni, Raffaella Zannolli, Wim Brussel
    Abstract:

    In patients with guanidinoacetate methyltransferase (GAMT) deficiency several parameters may point towards the diagnosis of GAMT deficiency. These include the low levels of creatine and creatinine in urine, the high concentration of guanidinoacetic acid (GAA) in urine and the low levels of creatine and creatinine in the cerebrospinal fluid (CSF). In this study, body fluids from 10 GAMT deficient patients were analysed using (1)H NMR Spectroscopy. The urine 1D (1)H NMR spectra of all the patients showed a doublet resonance at 3.98 ppm (pH 2.50) derived from GAA present in high concentration. For this compound, a good recovery and good correlation was found between an LC-MS/MS method and (1)H NMR Spectroscopy. In CSF NMR spectra of these patients, the singlet resonances of creatine and creatinine (3.05 and 3.13 ppm, respectively) were absent (normally always present in (1)H NMR spectra of CSF). Due to overlap by other resonances, the doublet of GAA could not be observed. Our data demonstrate that (1)H NMR Spectroscopy of urine and CSF can be used to diagnose patients with GAMT deficiency.

  • defect in dimethylglycine dehydrogenase a new inborn error of metabolism NMR Spectroscopy study
    Clinical Chemistry, 1999
    Co-Authors: Sytske H Moolenaar, Barbara A Binzak, Jo Poggibach, Jerry Vockley, Jacqueline M B Corstiaensen, Jan G N De Jong, Arend Heerschap, Udo F H Engelke, Ron A Wevers
    Abstract:

    Background: A38-year-old man presented with a history of fish odor (since age 5) and unusual muscle fatigue with increased serum creatine kinase. Our aim was to identify the metabolic error in this new condition. Methods: We used 1H NMR Spectroscopy to study serum and urine from the patient. Results: The concentration of N,N-dimethylglycine (DMG) was increased ∼100-fold in the serum and ∼20-fold in the urine. The presence of DMG as a storage product was confirmed by use of 13C NMR Spectroscopy and gas chromatography–mass spectrometry. The high concentration of DMG was caused by a deficiency of the enzyme dimethylglycine dehydrogenase (DMGDH). A homozygous missense mutation was found in the DMGDH gene of the patient. Conclusions: DMGDH deficiency must be added to the differential diagnosis of patients complaining of a fish odor. This deficiency is the first inborn error of metabolism discovered by use of in vitro 1H NMR Spectroscopy of body fluids.

  • 1H NMR Spectroscopy of body fluids in patients with inborn errors of purine and pyrimidine metabolism
    Journal of Inherited Metabolic Disease, 1997
    Co-Authors: Ron A Wevers, Arend Heerschap, Udo F H Engelke, Jan J. Rotteveel, J.g.n. De Jong, R. A. De Abreu
    Abstract:

    1H NMR Spectroscopy of body fluids has been used in the diagnosis of many inborn errors of metabolism (Lehnert and Hunkler 1986; Iles and Chalmers 1988). To our knowledge there is no systematic study available of body fluids from patients with inborn errors in the purine or pyrimidine metabolism. The main advantage of the technique over others that are used diagnostically in the screening for inborn errors of metabolism is the minimal sample pretreatment required for NMR Spectroscopy. Fractionation, extraction or derivatization of metabolites is not required. A further advantage is the overall view of proton-containing metabolites. Quantification of metabolites is possible. An obvious disadvantage is the substantial cost of high-field NMR spectrometers that are required for this work. This paper demonstrates that NMR Spectroscopy can be used in diagnosing inborn errors in purine and pyrimidine metabolism. Examples are given of NMR spectra of body fluids from patients with dihydropyrimidine dehydrogenase deficiency (McKusick 274270) and with dihydropyrimidinase deficiency (McKusick 222748).

Stefan Berger - One of the best experts on this subject based on the ideXlab platform.

R. A. De Abreu - One of the best experts on this subject based on the ideXlab platform.

  • 1H NMR Spectroscopy of body fluids in patients with inborn errors of purine and pyrimidine metabolism
    Journal of Inherited Metabolic Disease, 1997
    Co-Authors: Ron A Wevers, Arend Heerschap, Udo F H Engelke, Jan J. Rotteveel, J.g.n. De Jong, R. A. De Abreu
    Abstract:

    1H NMR Spectroscopy of body fluids has been used in the diagnosis of many inborn errors of metabolism (Lehnert and Hunkler 1986; Iles and Chalmers 1988). To our knowledge there is no systematic study available of body fluids from patients with inborn errors in the purine or pyrimidine metabolism. The main advantage of the technique over others that are used diagnostically in the screening for inborn errors of metabolism is the minimal sample pretreatment required for NMR Spectroscopy. Fractionation, extraction or derivatization of metabolites is not required. A further advantage is the overall view of proton-containing metabolites. Quantification of metabolites is possible. An obvious disadvantage is the substantial cost of high-field NMR spectrometers that are required for this work. This paper demonstrates that NMR Spectroscopy can be used in diagnosing inborn errors in purine and pyrimidine metabolism. Examples are given of NMR spectra of body fluids from patients with dihydropyrimidine dehydrogenase deficiency (McKusick 274270) and with dihydropyrimidinase deficiency (McKusick 222748).