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  • Wiley-Blackwell  (2)
  • American Association for the Advancement of Science (AAAS)  (1)
  • 1
    ISSN: 0899-0042
    Keywords: pharmacokinetics ; metabolism ; stereoselectivity ; protein binding ; binding site ; displacement ; metabolic chiral inversion ; chiral HPLC ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The present study was an attempt to elucidate the relationship between stereoselective pharmacokinetics and protein binding of KE-298 and its active metabolites, deacetyl-KE-298 (M-1) and S-methyl-KE-298 (M-2). Metabolic chiral inversion was also investigated. The levels of unchanged KE-298 in plasma after oral administration of (+)-(S)-KE-298 to rats were lower than those of (-)-(R)-KE-298, whereas the levels of M-1 and M-2 after administration of (+)-(S)-KE-298 were higher than after (-)-(R)-KE-298. In vitro, rat plasma protein binding of (+)-(S)-KE-298 was lower than that of (-)-(R)-KE-298. In contrast, the binding of (+)-(S)-M-1 and (+)-(S)-M-2 was higher than that of (-)-(R)-M-1 and (-)-(R)-M-2. Displacement studies revealed that the (+)-(S) and (-)-(R)-enantiomers of KE-298 and their metabolites bound to the warfarin binding site on rat serum albumin. These results suggest that the stereoselective plasma levels in KE-298 and its metabolites were closely related to enantiomeric differences in protein binding, attributed to quantitative differences in binding to albumin rather than to the different binding sites. Unidirectional chiral inversion was detected after oral administration of either (-)-(R)-KE-298 or (-)-(R)-M-2 to rats both yielding (+)-(S)-M-2. Chirality 9:22-28, 1997 © 1997 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 21 (1992), S. 285-291 
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A strategy for thermospray liquid chromatography/tandem mass spectrometry (TSP LC/MS/MS) of very thermally labile xenobiotic conjugates, such as acetaminophen (AA) conjugates, selected as model compounds in biological fluid, was examined. The vaporizer temperature as well as collision energy were optimized using authentic AA-glutathione conjugate without modification of any analytical conditions, including mobile-phase composition, ion source temperature and repeller voltage. The [MH]+ ion intensities in the parent ion mass spectrum of m/z 182 from the conjugate at a collision energy of -25 eV were improved and maximized with a lowering of the vaporizer temperature from 115°C, corresponding to the optimal vaporization temperature of the mobile phase, to 80°C. Bile obtained from rats was treated with an equimolar mixture of AA and (2H3)AA was directly injected into the TSP LC/MS/MS system to perform the metabolic mapping of AA. The glucuronic acid, sulphuric acid, glutathione and cysteinylglycine conjugates of AA, in addition to the parent drug, were detectable by the parent ion scan mode, and confirmation of each structure could be obtained by the daughter ion scan mode. These conjugates appeared to show a marked temperature effect on the quality of TSP tandem mass spectra and sensitivity.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2018-02-03
    Description: Inorganic carbon fixation is essential to sustain life on Earth, and the reductive tricarboxylic acid (rTCA) cycle is one of the most ancient carbon fixation metabolisms. A combination of genomic, enzymatic, and metabolomic analyses of a deeply branching chemolithotrophic Thermosulfidibacter takaii ABI70S6 T revealed a previously unknown reversible TCA cycle whose direction was controlled by the available carbon source(s). Under a chemolithoautotrophic condition, a rTCA cycle occurred with the reverse reaction of citrate synthase (CS) and not with the adenosine 5'-triphosphate–dependent citrate cleavage reactions that had been regarded as essential for the conventional rTCA cycle. Phylometabolic evaluation suggests that the TCA cycle with reversible CS may represent an ancestral mode of the rTCA cycle and raises the possibility of a facultatively chemolithomixotrophic origin of life.
    Keywords: Biochemistry, Microbiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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