Metabolism nuclear magnetic resonance

Dawson, M.J., Gadian, D.G., Wilkie, D.R. (1980). Mechanical relaxation rate and metabolism studied in fatiguing muscle by phosphorus nuclear magnetic resonance. J. Physiol. 299,465-484. 

Metabolomics studies the entire metabolism of an organism. It is possible to consider characterising the complex pattern of cellular proteins and metabolites that are excreted in urine. Pattern recognition techniques of nuclear magnetic resonance spectra have been applied to determine the dose-response using certain classical liver and kidney toxicants (Robertson et al, 2000). This could well provide a signature of the functional state of the kidney, and perturbations in the pattern as a result of exposure to a chemical could be observed. But first it would be necessary to understand how compounds with known effects on the kidney affect these processes. 

Halpin RA, GD Hegeman, GL Kenyon (1981) Carbon-13 nuclear magnetic resonance studies of mandelate metabolism in whole bacterial cells and in isolated, in vivo cross-linked enzyme complexes. Biochemistry 20 1525-1533. 

Parisot D, MC Malet-Martino, P Crasnier, R Martino (1989) nuclear magnetic resonance analysis of 5-fluorouracil metabolism in wild-type and 5-fluorouracil-resistant Nectria haematococca. Appl Environ Microbiol 55 2474-2479. 

Ansede JH, PJ Pellechia, DC Yoch (2001) Ansede JH, PJ Pellechia, DC Yoch (2001) Nuclear magnetic resonance analysis of [l- C]dimethylsulfoniopropionate (DMSP) and [l- C]acrylate metabolism by a DMSP lyase-producing marine isolate of the a-subclass proteobacteria. Appl Environ Microbiol 67 3134-3139. 

Naughton, D., Whelan, M., Smith, E.C., Williams, R., Blake, D.R. and Grootveld, M. (1993). An investigation of the abnormal metabolic status of synovial fluid from patients with rheumatoid arthritis by high field proton nuclear magnetic resonance spectroscopy. FEBS Lett. 317, 135-138. 

Nomier AA, Abou-Donia MB. 1986. Studies on the metabolism of the neurotoxic tri-ort/20-cresyl phosphate Synthesis and identification by infrared, proton nuclear magnetic resonance and mass spectrometry of five of its metabolites. Toxicology 38 1-13. 

Nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research has been used primarily in a classical, organic chemistry framework. Typical studies have included (1) the structure elucidation of compounds [1,2], (2) investigating chirality of drug substances [3,4], (3) the determination of cellular metabolism [5,6], and (4) protein studies [7-9], to name but a few. From the development perspective, NMR is traditionally used again for structure elucidation, but also for analytical applications [10]. In each case, solution-phase NMR has been utilized. It seems ironic that although —90% of the pharmaceutical products on the market exist in the solid form, solid state NMR is in its infancy as applied to pharmaceutical problem solving and methods development. 

Carbon-13 nuclear magnetic resonance spectroscopy is a powerful method for studying brain metabolism. 

Pettegrew, J. W., Keshavan, M. S., Panchalingam, K. et al. Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drug-naive schizophrenics. A pilot study of the dorsal prefrontal cortex by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy. Arch. Gen. Psychiat. 48 563-568,1991. 

K. Nicolay, K. J. Hellingwerg, R. Kaptein, W. N. Konings (1982) Carbon-13 nuclear magnetic resonance studies of acetate metabolism in intact cells of Rhodopsedomonas sphaeroides, Biochimica etBiophysiea Acta, 250-258... 

Benabid MAS, Decorps M, Remy C. 1987. 3 IP nuclear magnetic resonance in vivo spectroscopy of the metabolic changes induced in the awake rat brain during KCN intoxication and its reversal by hydroxocobalamine. JNeurochem 48 804-808. 

Nuclear magnetic resonance (NMR) spectroscopy of untreated biological fluids has been used successfully in metabolic studies of penicillins. Connor et al. [153] used this method to investigate the metabolism and urinary excretion of ampicillin and amoxycillin in humans and rats. In addition to the metabolites 5.49 and 5.50, they detected a dimer of amoxycillin (5.51) in rat urine. 

Because muscle cells are especially rich in terms of phosphorus-containing metabolites (e.g., ATP, ADP, phos-phocreatine, and orthophosphate), nuclear magnetic resonance " has proved to be a valuable noninvasive probe of metabolic changes attending muscle activity. The spectral sensitivity of P is especially high relative to other nuclei, and one can detect cellular concentrations as low as 0.5 mM as well as utilize chemical shift data to define intracellular pH and free magnesium ion concentrations. See also Nuclear Magnetic Resonance Chemical Shift... 

R. Martino, M. Malet-Martino, V. Gilard, Fluorine nuclear magnetic resonance, a privileged tool for metabolic studies of fluoropyrimidine drugs, Curr. Drug Metab. 1 (2000) 271-303. 

B.S. Selinsky, M.E. Perlman, R.E. London, In vivo nuclear magnetic resonance studies of hepatic methoxyflurane metabolism. I. Verification and quantitation of methoxydifluoroacetate. Mol. Pharmacol. 33 (1988) 559-566. 

T. Nakada, I.L. Kwee, C.B. Conboy, Noninvasive in vivo denonstratlon of 2-fluoro-2-deoxy-D-glucose metabolism beyond the hexokinase reaction In rat-brain by F-19 nuclear-magnetic-resonance spectroscopy. J. Neurochem. 46 (1986) 198. 

Compared with chiroptical methods and nuclear magnetic resonance spectroscopy (NMR), only chiral chromatography by direct and indirect methods is suitable for the accurate determination of enantiomeric impurities of less than 1% and for quantitative stereochemical analyses of small sample amounts (for example, in vivo studies of the metabolic pathway or pharmacokinetic effects of chiral pharmaceuticals.)... 

D. Morvan, A. Demidem, J. Papon, M. De Latour and J. C. Madelmont, Melanoma tumors acquire a new phospholipid metabolism phenotype under cystemustine as revealed by high-resolution magic angle spinning proton nuclear magnetic resonance spectroscopy of intact tumor samples, Cancer Res., 2002, 62, 1890-1897. 

Linhart, I., Hrabal, R., Smejkal, J. Mitera, J. (1994a) Metabolic pathways of l-butyl[3- C]-acrylate. Identification of urinary metabolites in rat using nuclear magnetic resonance and mass spectroscopy. Chem. Res. Toxicol. 7, 1-8... 

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