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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 9 (1992), S. 1465-1473 
    ISSN: 1573-904X
    Keywords: lipoxygenase ; 5-lipoxygenase inhibitor ; kinetics ; borate catalysis ; N-hydroxyurea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Zileuton (N-(1-benzo[b]thien-2-ylethyl)N-hydroxyurea) is a powerful 5-lipoxygenase inhibitor. The chemical degradation of Zileuton and related hydroxyurea derivatives was studied in aqueous solutions as a function of pH and temperature. The pH profile for the degradation of Zileuton shows an acid-catalyzed region at pH values below 2, water hydrolysis of the protonated form at pH values from 3 to 8, and water hydrolysis of the unprotonated form at pH values greater than 9. Hydrolysis of the hydroxyurea moiety to give the hydroxylamine derivative represents the main degradation pathway for Zileuton. This product, however, is not stable and is present at low concentrations at pH values below 6 and not observed at pH values greater than 7. Further decomposition of the hydroxylamine derivative leads to the observed degradation products. Air oxidation to the isomeric oximes accounts for the observed products at pH values greater than 7. Hydrolysis of the oximes to the ketone derivative accounts for the observed products at pH values 2 to 6. Parallel decomposition pathways to the alcohol derivative were noted under strongly acidic conditions, pH 0 to 2.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: pancreatic lipase ; lipase ; lipolysis ; triglycerides ; kinetics ; mechanism ; calcium ; bile salts ; lecithin ; emulsions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Lecithin-stabilized triglyceride emulsions are subject to hydrolysis by pancreatic lipase. The time profiles of these reactions are characterized by a lag-phase and a zero-order phase. Lag phases are more pronounced with long-chain triglycerides. Ca2+ is effective in reducing the lag-phase and activating lipase. Kinetic analysis of the reactions suggests that, like previous findings by others, taurodeoxycholate (TDC) micellar solutions combine with the lipase–colipase complex to form another catalytically active enzyme form. This enzyme form exhibits reduced activity in the absence of Ca2+. In the presence of Ca2+ the mixed micelle–lipase complex becomes more active and opens a new pathway for lipolysis. It is suggested that this enzyme form can bind more easily to interfaces with different physicochemical properties. Under these conditions, Ca2+ activates the lipolysis of short-, medium-, and long-chain triglycerides by a similar mechanism. Maximum activities were measured in the presence of approximately 6 mM TDC and 30 mM Ca2+. The experimental conditions approximate the physiological conditions in the gastrointestinal tract since all of the factors studied here have been reported to be necessary for in vivo lipolysis and/or absorption of triglycerides. A mechanistic model for lipolysis in the presence of Ca2+ and the bile salt TDC is proposed which accounts for most of the experimental observations in a quantitative manner.
    Type of Medium: Electronic Resource
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