1-pyrenebutanol and 7-benzyloxyquinoline

1-pyrenebutanol has been researched along with 7-benzyloxyquinoline* in 2 studies

Other Studies

2 other study(ies) available for 1-pyrenebutanol and 7-benzyloxyquinoline

ArticleYear
Effect of glutathione on homo- and heterotropic cooperativity in cytochrome P450 3A4.
    Archives of biochemistry and biophysics, 2008, Mar-15, Volume: 471, Issue:2

    Glutathione (GSH) exerted a profound effect on the oxidation of 7-benzyloxy-4-(trifluoromethyl)coumarin (BFC) and 7-benzyloxyquinoline (BQ) by human liver microsomes as well as by CYP3A4-containing insect cell microsomes (Baculosomes). The cooperativity in O-debenzylation of both substrates is eliminated in the presence of 1-4mM GSH. Addition of GSH also increased the amplitude of the 1-PB induced spin shift with purified CYP3A4 and abolished the cooperativity of 1-PB or BFC binding. Changes in fluorescence of 6-bromoacetyl-2-dimethylaminonaphthalene attached to the cysteine-depleted mutant CYP3A4(C58,C64) suggest a GSH-induced conformational changes in proximity of alpha-helix A. Importantly, the K(S) value for formation of the GSH complex and the concentrations in which GSH decreases CYP3A4 cooperativity are consistent with the physiological concentrations of GSH in hepatocytes. Therefore, the allosteric effect of GSH on CYP3A4 may play an important role in regulation of microsomal monooxygenase activity in vivo.

    Topics: 2-Naphthylamine; Allosteric Site; Aryl Hydrocarbon Hydroxylases; Binding Sites; Coumarins; Cysteine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Glutathione; Humans; Kinetics; Microsomes, Liver; Mutation; Oxidation-Reduction; Protein Structure, Secondary; Pyrenes; Quinolines; Spectrometry, Fluorescence; Substrate Specificity

2008
Homotropic versus heterotopic cooperativity of cytochrome P450eryF: a substrate oxidation and spectral titration study.
    Drug metabolism and disposition: the biological fate of chemicals, 2003, Volume: 31, Issue:4

    P450eryF is the only bacterial P450 to show cooperativity of substrate binding and oxidation. However, the studies reported so far have provided evidence only for homotropic cooperativity of P450eryF but not for heterotropic cooperativity. Therefore, oxidation of 7-benzyloxyquinoline (7-BQ) and 1-pyrenebutanol (1-PB) by P450eryF A245T and spectral binding of 9-aminophenanthrene (9-AP) to wild-type P450eryF were investigated in the presence of various effectors. The addition of steroids and flavones caused no stimulation but rather moderate inhibition of 7-BQ or 1-PB oxidation by P450eryF A245T. However, the binding affinity of 9-AP was significantly increased in the presence of androstenedione or alpha-naphthoflavone (ANF). A comparative study with CYP3A4 revealed a similar increase in the binding affinity of 9-AP for the enzyme at low ANF concentrations but some competition at higher ANF concentrations. These studies, to our knowledge, provide the first report of heterotropic cooperativity in P450eryF as well as spectroscopic evidence for simultaneous presence of two ligand molecules in the CYP3A4 active site.

    Topics: Alanine; Androstenedione; Atrial Natriuretic Factor; Bacteria; Bacterial Proteins; Binding Sites; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Flavones; Flavonoids; In Vitro Techniques; Mixed Function Oxygenases; Mutagenesis, Site-Directed; Oxidation-Reduction; Pyrenes; Quinolines; Structure-Activity Relationship; Substrate Specificity; Threonine; Titrimetry

2003